川芎嗪干预大鼠缺血性中风作用及其机制的研究
|
摘要
中风是严重危害人类健康和生命安全的常见难治性疾病。祖国医学将其列为“风、痨、臌、膈”四大疑难病之首,存在着明显三高(发病率高、致残率高、死亡率高)现象。因而,提高中风的治疗与预防水平、降低中风的发病率,致残率和死亡率是当务之急。缺血性中风占所有中风的85%,因此研究缺血性中风的发病原因、机制及其防治对策,既有极其重要的社会现实意义,又具有较高的理论价值和临床实际意义。
论文工作包括综述和实验研究两个部分。
一、综述缺血性中风及其中药治疗相关研究的进展
(一)系统概述了缺血性中风发病中能量代谢障碍、梗塞周围去极化、氧化应激损伤、炎症反应和细胞凋亡的发生、发展机制。
(二)重点介绍了缺血性中风发病过程中由炎症反应和氧化应激损伤介导的信号转导通路研究进展,
(三)重点介绍了川芎嗪在缺血性中风临床和基础研究方面的进展。明确这些研究领域的进展,将为本研究奠定坚实的理论基础,并为实验研究设计提供前提条件。
二、实验研究
(一)研究方法
采用病理组织学方法、免疫组织化学方法、现代分子生物学方法。
(二)技术手段
采用流式细胞仪分析、定量RT-PCR基因检测、免疫印迹、免疫荧光双标法和化学比色法等技术。
(三)检测指标
1.脑损伤指标：脑梗塞面积、血脑屏障通透性、脑皮质含水量
2.氧化应激相关因子：MDA、NO、CAT、GSH-Px。
3.免疫指标
(1)免疫细胞：中性粒细胞和T淋巴细胞数量、巨噬细胞/小胶质细胞的静息与活化的比值。
(2)炎症介质：MPO、TNF-α和IL-1β。,
4.信号转导分子：即早基因c-fos和c-jun、p-c-jun、Fos蛋白、Jun蛋白、JNK、AP-1、HO-1、Nrf2。
(四)结果与结论
1实验一川芎嗪对缺血性中风大鼠神经组织损伤及其功能的影响
(1)实验制备的缺血性中风大鼠模型可靠：在实验大鼠脑组织发生了明确的脑组织损伤(脑梗塞、血脑屏障破坏和脑水肿),并伴发神经行为学改变；
(2)川芎嗪对缺血性中风大鼠发生了明确的药理学干预作用：表现为减小脑梗塞的面积,减轻脑水肿和血脑屏障损伤程度,改善大鼠神经行为异常。提示：川芎嗪具有一定的神经保护作用。
2实验二川芎嗪对缺血性中风大鼠氧化应激反应的影响
(1)缺血性中风大鼠永久性脑缺血受损皮质组织发生了过氧化反应：
MDA含量增加,中性粒细胞NO含量升高,CAT、GSH-Px活性有增高趋势；
(2)川芎嗪可降低缺血性中风大鼠脑缺血受损皮质组织过氧化程度：
川芎嗪可下调MDA含量和中性粒细胞NO含量；
川芎嗪可上调抗氧化物质CAT、GSH-Px活性
提示：川芎嗪干预缺血性中风机制中,抑制氧化应激损伤可能是其机制之一。
3实验三川芎嗪对缺血性中风炎症反应的影响的实验研究
(1)缺血性脑中风大鼠产生了明显的炎症反应：
伤害侧皮质组织内CD45阳性的免疫细胞数量增多,巨噬细胞/小胶质细胞被激活数量增多；
伤害侧皮质组织内MPO活性及CD68表面抗原蛋白表达量增多；
(2)川芎嗪可干预缺血性中风大鼠的炎症反应：
下调免疫细胞数量和活化的巨噬细胞/胶细胞数量,
下调脑缺血造成受损皮质组织MPO活性及CD68表面抗原蛋白表达量。
提示：川芎嗪干预缺血性中风机制中,抑制炎症反应可能是其重要机制之一
4实验四川芎嗪对缺血性中风大鼠缺血诱导激活的信号转导通路的影响的实验研究
(1)证实缺血性中风大鼠缺血脑组织启动的炎症反应信号转导通路之一是JNK/AP-1信号转导通路；
川芎嗪干预缺血性中风大鼠过程中的抗炎作用机制：抑制AP-1DNA结合活性,限制或减弱转录蛋白c-Fos蛋白质c-Jun蛋白质和JNK蛋白磷酸化。
提示：川芎嗪阻断或削弱JNK/AP-1炎症反应信号转导通路,从而实现抗炎和保护脑组织作用。
(2)证实缺血性中风大鼠缺血脑组织启动氧化应激信号转导通路之一是Nrf2/ARE通路。
川芎嗪干预缺血性中风大鼠的抗氧化应激的作用机制：进一步上调HO-1和Nrf2免疫荧光细胞数量、上调Nrf2和HO-1蛋白表达量。提示：川芎嗪可激活Nrf2/ARE通路,促使Ⅱ相酶HO-1释放,发挥清除自由基抗氧化作用,以减少脑组织的损伤。
三、本课题研究的创新点
(一)通过“川芎嗪干预缺血性中风作用的信号转导通路机制研究”,证实川芎嗪干预缺血性中风作用过程中,炎症反应和氧化应激损伤所介导的信号转导通路包括JNK/AP-1通路和Nrf2/ARE通路。
(二)以缺血性中风氧化应激损伤为目标,重点观察了川芎嗪对缺血性中风大鼠受损皮质组织MDA、NO、Catalase和GPx作用的影响。证实川芎嗪可降低永久性脑缺血所引发的过氧化程度。
(三)以缺血性中风炎症反应为目标,重点研究了川芎嗪对缺血性中风大鼠永久性缺血受损皮质组织免疫细胞(中性粒细胞、T淋巴细胞、巨噬细胞／小胶质细胞等)和炎症因子(TNF-α、IL-1β、MPO等)的影响。证实川芎嗪通过下调免疫细胞和炎症因子的方式来发挥抗炎作用。
Stroke is a common refractory disease and a serious hazard to human health and safety. It is even considered as one of the four incurable diseases including "stroke, consumption, bloating, dysphagia" in Chinese medicine. Due to its characteristics of high incidence, high morbidity and high mortality, it has become a priority for this disease for reducing the incidence of stroke morbidity/mortality, and improving prevention and treatment of stroke. Because85percent of all stroke cases are due to ischemic event, it is becoming more important to explore pathogenesis, mechanisms and counter measures of ischemic stroke in theoretical value and clinical practice.
The work of this paper includes two parts, review and experimental research.
1. Ischemic stroke and the research progress in the treatment of ischemic stroke with Chinese medicine
This study systemically reviewed the development of the pathogenesis of ischemic stroke, the development of the signal transduction pathways involved in ischemic cerebral stroke from ischemic injury and the research progress in the treatment of ischemic stroke with Chinese medicine. It systemically summarized the obstacle of energy metabolism during ischemic stroke, peri-infarct depolarization, oxidative stress, inflammation and mechanism of apoptosis. It focused on the research progress of the inflammation and oxidative stress-mediated signaling transduction pathways in the pathogenesis of ischemic stroke, the clinical and basic research of tetramethylpyrazine (TMP) progress in ischemic stroke. Clarifying all of these progresses in the research was to lay a solid theoretical foundation for this study and provided preconditions for the experimental design.
2Experimental research
2.1Research methods
Experimental study using histopathological method, immunohistochemical method, modern molecular biological techniques.
2.2Technical manipulations
Flow cytometry, Real-time RT-PCR for gene detection, quantitative immunoblotting, immunofluorescence method and chemical colorimetry technique.
2.3Detection index
2.3.1Brain injury index:the area of cerebral infarction, blood-brain barrier permeability, cerebral water content.
2.3.2Oxidative stress related factors:MDA, NO, CAT, GSH-Px.
2.3.3Immune index
2.3.3.1Immune cells, neutrophils and T lymphocytes, macrophage/microglial resting and activated ratio.
2.3.3.2Inflammatory mediators:MPO, TNF-α and IL-1β.
2.3.4Signal transduction molecule:the immediate early genes c-fos and c-jun, p-c-jun, Fos protein, Jun protein, JNK, AP-1, HO-1, Nrf2.
2.4The research results
2.4.1Experiment1Effect of Tetramethylpyrazine on experimental neuron-tissue injury and function of ischemic stroke in rats
2.4.1.1A reliable Ischemicstroke rat model from experimental preparation:
Clear and definite brain tissue injury in experimental rats (cerebral infarction, blood-brain barrier damage and brain edema), and concomitant neurological behavioral changes;
2.4.1.2Tetramethylpyrazine has clear and definite pharmacological intervention on ischemic stroke rats:
To express the reduction of cerebral infarction area, reduce brain edema and blood-brain barrier damage, improve the abnormal neurological behavior of rat. Suggestion:Tetramethylpyrazine has a neuroprotective effect.
2.4.2Experiment2Effect of Tetramethylpyrazine on oxidative stress reaction of rats with ischemic stroke
2.4.2.1The peroxidation of permanent cerebral ischemia of ischemic stroke in the rat with damaged cortical tissue
The increase of MDA content, increased content of NO in neutrophils, CAT, GSH-Px activity had increased trend;
2.4.2.2Tetramethylpyrazine can reduce peroxidation of damaged cortical tissue of rat with cerebral ischemic stroke:
Tetramethylpyrazine may reduce the content of MDA and content of NO in neutrophils.
Tetramethylpyrazine may increase the activity of antioxidant CAT, GSH-Px.
Suggestion:intervention mechanism of Tetramethylpyrazine on ischemic stroke, inhibiting oxidative stress injury may be one of its mechanisms.
2.4.3Experimental3Study of on inflammatory reaction of ischemic stroke
2.4.3.1Ischemic stroke of rats produced obvious inflammation:
2.4.3.1.1On injury cortex tissue, the number of CD45positive immune cells increased and the number of macrophages/microglia activated increased;
2.4.3.1.2On injury cortex tissue, the expression increased of MPO activity and CD68surface antigen protein;
2.4.3.2Tetramethylpyrazine interventing in inflammation of ischemic stroke in rats:
To down-regulation of immune cells number and activated macrophages/microglia number.
To down-regulation of MPO activity and CD68surface antigen protein expression of impaired cortical tissue caused by cerebral ischemia.
Suggestion:intervention mechanism of Tetramethylpyrazine in ischemic stroke, inhibit inflammatory reaction may be one of the important mechanisms.
2.4.4Experimental4Experimental study of Tetramethylpyrazine on signal transduction pathway induced and activated by ischemia in rats with ischemic stroke.
2.4.4.1Confirmed one of the inflammatory signal transduction pathway initi ated by ischemic brain tissue in rats with ischemic stroke is JNK/AP-1pathway.
The anti-inflammatory mechanism of Tetramethylpyrazine intervention of ischemic stroke in rats:the inhibition of AP-1DNA binding activity, restricted or decreased transcription protein c-Fos protein, c-Jun protein and JNK protein phosphorylation.
Suggestion:Tetramethylpyrazine block or weaken the JNK/AP-1inflamm ation signal transduction pathway, so as to achieve the effect of anti-inflammati on and protect the brain tissue.
2.4.4.2Confirmed one of the oxidative stress signal transduction pathway initiated by ischemic brain tissue in rats with ischemic stroke is Nrf2/ARE pathway.
Effect and mechanism of antioxidant stress of Tetramethylpyrazine invent ischemia rats with ischemic stroke:further up regulation of immunofluor escence cells number of HO-1and Nrf2, up-regulating expression of Nrf2and HO-1protein.
Suggestion:Tetramethylpyrazine may activate Nrf2/ARE pathway, the phase Ⅱ enzymes of HO-1release, antioxidation and clear the free radical, in order to reduce the injury of brain tissue.
3. Innovation of the research
3.1It is the first time to study the mechanisms of signal transduction pathway of TMP intervening in ischemic stroke.
It confirmed that the pathways of TMP intervening in ischemic stroke are JNK/AP-1and Nrf2/ARE pathway in inflammation and oxidative stress-mediated signal transduction.
3.2This study observed the effects of TMP focus on MDA, NO, Catalase and GPx role of damaged cortical tissue of ischemic stroke in rats with injury of oxidative stress as a target. It determined that TMP can reduce peroxidation caused by permanent brain ischemia.
3.3This study focused on the effects of TMP on damaged cortical tissue immune cells of permanent ischemic stroke in rat (neutrophils, T lymphocytes, macrophages/microglia) and inflammatory cytokines (TNF-α, IL-1β, MPO, etc.) with inflammatory response of ischemic stroke as a target.
It confirmed that TMP anti-inflammatory effect is by down-regulating immune cells and inflammatory cytokines way.
论文工作包括综述和实验研究两个部分。
一、综述缺血性中风及其中药治疗相关研究的进展
(一)系统概述了缺血性中风发病中能量代谢障碍、梗塞周围去极化、氧化应激损伤、炎症反应和细胞凋亡的发生、发展机制。
(二)重点介绍了缺血性中风发病过程中由炎症反应和氧化应激损伤介导的信号转导通路研究进展,
(三)重点介绍了川芎嗪在缺血性中风临床和基础研究方面的进展。明确这些研究领域的进展,将为本研究奠定坚实的理论基础,并为实验研究设计提供前提条件。
二、实验研究
(一)研究方法
采用病理组织学方法、免疫组织化学方法、现代分子生物学方法。
(二)技术手段
采用流式细胞仪分析、定量RT-PCR基因检测、免疫印迹、免疫荧光双标法和化学比色法等技术。
(三)检测指标
1.脑损伤指标：脑梗塞面积、血脑屏障通透性、脑皮质含水量
2.氧化应激相关因子：MDA、NO、CAT、GSH-Px。
3.免疫指标
(1)免疫细胞：中性粒细胞和T淋巴细胞数量、巨噬细胞/小胶质细胞的静息与活化的比值。
(2)炎症介质：MPO、TNF-α和IL-1β。,
4.信号转导分子：即早基因c-fos和c-jun、p-c-jun、Fos蛋白、Jun蛋白、JNK、AP-1、HO-1、Nrf2。
(四)结果与结论
1实验一川芎嗪对缺血性中风大鼠神经组织损伤及其功能的影响
(1)实验制备的缺血性中风大鼠模型可靠：在实验大鼠脑组织发生了明确的脑组织损伤(脑梗塞、血脑屏障破坏和脑水肿),并伴发神经行为学改变；
(2)川芎嗪对缺血性中风大鼠发生了明确的药理学干预作用：表现为减小脑梗塞的面积,减轻脑水肿和血脑屏障损伤程度,改善大鼠神经行为异常。提示：川芎嗪具有一定的神经保护作用。
2实验二川芎嗪对缺血性中风大鼠氧化应激反应的影响
(1)缺血性中风大鼠永久性脑缺血受损皮质组织发生了过氧化反应：
MDA含量增加,中性粒细胞NO含量升高,CAT、GSH-Px活性有增高趋势；
(2)川芎嗪可降低缺血性中风大鼠脑缺血受损皮质组织过氧化程度：
川芎嗪可下调MDA含量和中性粒细胞NO含量；
川芎嗪可上调抗氧化物质CAT、GSH-Px活性
提示：川芎嗪干预缺血性中风机制中,抑制氧化应激损伤可能是其机制之一。
3实验三川芎嗪对缺血性中风炎症反应的影响的实验研究
(1)缺血性脑中风大鼠产生了明显的炎症反应：
伤害侧皮质组织内CD45阳性的免疫细胞数量增多,巨噬细胞/小胶质细胞被激活数量增多；
伤害侧皮质组织内MPO活性及CD68表面抗原蛋白表达量增多；
(2)川芎嗪可干预缺血性中风大鼠的炎症反应：
下调免疫细胞数量和活化的巨噬细胞/胶细胞数量,
下调脑缺血造成受损皮质组织MPO活性及CD68表面抗原蛋白表达量。
提示：川芎嗪干预缺血性中风机制中,抑制炎症反应可能是其重要机制之一
4实验四川芎嗪对缺血性中风大鼠缺血诱导激活的信号转导通路的影响的实验研究
(1)证实缺血性中风大鼠缺血脑组织启动的炎症反应信号转导通路之一是JNK/AP-1信号转导通路；
川芎嗪干预缺血性中风大鼠过程中的抗炎作用机制：抑制AP-1DNA结合活性,限制或减弱转录蛋白c-Fos蛋白质c-Jun蛋白质和JNK蛋白磷酸化。
提示：川芎嗪阻断或削弱JNK/AP-1炎症反应信号转导通路,从而实现抗炎和保护脑组织作用。
(2)证实缺血性中风大鼠缺血脑组织启动氧化应激信号转导通路之一是Nrf2/ARE通路。
川芎嗪干预缺血性中风大鼠的抗氧化应激的作用机制：进一步上调HO-1和Nrf2免疫荧光细胞数量、上调Nrf2和HO-1蛋白表达量。提示：川芎嗪可激活Nrf2/ARE通路,促使Ⅱ相酶HO-1释放,发挥清除自由基抗氧化作用,以减少脑组织的损伤。
三、本课题研究的创新点
(一)通过“川芎嗪干预缺血性中风作用的信号转导通路机制研究”,证实川芎嗪干预缺血性中风作用过程中,炎症反应和氧化应激损伤所介导的信号转导通路包括JNK/AP-1通路和Nrf2/ARE通路。
(二)以缺血性中风氧化应激损伤为目标,重点观察了川芎嗪对缺血性中风大鼠受损皮质组织MDA、NO、Catalase和GPx作用的影响。证实川芎嗪可降低永久性脑缺血所引发的过氧化程度。
(三)以缺血性中风炎症反应为目标,重点研究了川芎嗪对缺血性中风大鼠永久性缺血受损皮质组织免疫细胞(中性粒细胞、T淋巴细胞、巨噬细胞／小胶质细胞等)和炎症因子(TNF-α、IL-1β、MPO等)的影响。证实川芎嗪通过下调免疫细胞和炎症因子的方式来发挥抗炎作用。
Stroke is a common refractory disease and a serious hazard to human health and safety. It is even considered as one of the four incurable diseases including "stroke, consumption, bloating, dysphagia" in Chinese medicine. Due to its characteristics of high incidence, high morbidity and high mortality, it has become a priority for this disease for reducing the incidence of stroke morbidity/mortality, and improving prevention and treatment of stroke. Because85percent of all stroke cases are due to ischemic event, it is becoming more important to explore pathogenesis, mechanisms and counter measures of ischemic stroke in theoretical value and clinical practice.
The work of this paper includes two parts, review and experimental research.
1. Ischemic stroke and the research progress in the treatment of ischemic stroke with Chinese medicine
This study systemically reviewed the development of the pathogenesis of ischemic stroke, the development of the signal transduction pathways involved in ischemic cerebral stroke from ischemic injury and the research progress in the treatment of ischemic stroke with Chinese medicine. It systemically summarized the obstacle of energy metabolism during ischemic stroke, peri-infarct depolarization, oxidative stress, inflammation and mechanism of apoptosis. It focused on the research progress of the inflammation and oxidative stress-mediated signaling transduction pathways in the pathogenesis of ischemic stroke, the clinical and basic research of tetramethylpyrazine (TMP) progress in ischemic stroke. Clarifying all of these progresses in the research was to lay a solid theoretical foundation for this study and provided preconditions for the experimental design.
2Experimental research
2.1Research methods
Experimental study using histopathological method, immunohistochemical method, modern molecular biological techniques.
2.2Technical manipulations
Flow cytometry, Real-time RT-PCR for gene detection, quantitative immunoblotting, immunofluorescence method and chemical colorimetry technique.
2.3Detection index
2.3.1Brain injury index:the area of cerebral infarction, blood-brain barrier permeability, cerebral water content.
2.3.2Oxidative stress related factors:MDA, NO, CAT, GSH-Px.
2.3.3Immune index
2.3.3.1Immune cells, neutrophils and T lymphocytes, macrophage/microglial resting and activated ratio.
2.3.3.2Inflammatory mediators:MPO, TNF-α and IL-1β.
2.3.4Signal transduction molecule:the immediate early genes c-fos and c-jun, p-c-jun, Fos protein, Jun protein, JNK, AP-1, HO-1, Nrf2.
2.4The research results
2.4.1Experiment1Effect of Tetramethylpyrazine on experimental neuron-tissue injury and function of ischemic stroke in rats
2.4.1.1A reliable Ischemicstroke rat model from experimental preparation:
Clear and definite brain tissue injury in experimental rats (cerebral infarction, blood-brain barrier damage and brain edema), and concomitant neurological behavioral changes;
2.4.1.2Tetramethylpyrazine has clear and definite pharmacological intervention on ischemic stroke rats:
To express the reduction of cerebral infarction area, reduce brain edema and blood-brain barrier damage, improve the abnormal neurological behavior of rat. Suggestion:Tetramethylpyrazine has a neuroprotective effect.
2.4.2Experiment2Effect of Tetramethylpyrazine on oxidative stress reaction of rats with ischemic stroke
2.4.2.1The peroxidation of permanent cerebral ischemia of ischemic stroke in the rat with damaged cortical tissue
The increase of MDA content, increased content of NO in neutrophils, CAT, GSH-Px activity had increased trend;
2.4.2.2Tetramethylpyrazine can reduce peroxidation of damaged cortical tissue of rat with cerebral ischemic stroke:
Tetramethylpyrazine may reduce the content of MDA and content of NO in neutrophils.
Tetramethylpyrazine may increase the activity of antioxidant CAT, GSH-Px.
Suggestion:intervention mechanism of Tetramethylpyrazine on ischemic stroke, inhibiting oxidative stress injury may be one of its mechanisms.
2.4.3Experimental3Study of on inflammatory reaction of ischemic stroke
2.4.3.1Ischemic stroke of rats produced obvious inflammation:
2.4.3.1.1On injury cortex tissue, the number of CD45positive immune cells increased and the number of macrophages/microglia activated increased;
2.4.3.1.2On injury cortex tissue, the expression increased of MPO activity and CD68surface antigen protein;
2.4.3.2Tetramethylpyrazine interventing in inflammation of ischemic stroke in rats:
To down-regulation of immune cells number and activated macrophages/microglia number.
To down-regulation of MPO activity and CD68surface antigen protein expression of impaired cortical tissue caused by cerebral ischemia.
Suggestion:intervention mechanism of Tetramethylpyrazine in ischemic stroke, inhibit inflammatory reaction may be one of the important mechanisms.
2.4.4Experimental4Experimental study of Tetramethylpyrazine on signal transduction pathway induced and activated by ischemia in rats with ischemic stroke.
2.4.4.1Confirmed one of the inflammatory signal transduction pathway initi ated by ischemic brain tissue in rats with ischemic stroke is JNK/AP-1pathway.
The anti-inflammatory mechanism of Tetramethylpyrazine intervention of ischemic stroke in rats:the inhibition of AP-1DNA binding activity, restricted or decreased transcription protein c-Fos protein, c-Jun protein and JNK protein phosphorylation.
Suggestion:Tetramethylpyrazine block or weaken the JNK/AP-1inflamm ation signal transduction pathway, so as to achieve the effect of anti-inflammati on and protect the brain tissue.
2.4.4.2Confirmed one of the oxidative stress signal transduction pathway initiated by ischemic brain tissue in rats with ischemic stroke is Nrf2/ARE pathway.
Effect and mechanism of antioxidant stress of Tetramethylpyrazine invent ischemia rats with ischemic stroke:further up regulation of immunofluor escence cells number of HO-1and Nrf2, up-regulating expression of Nrf2and HO-1protein.
Suggestion:Tetramethylpyrazine may activate Nrf2/ARE pathway, the phase Ⅱ enzymes of HO-1release, antioxidation and clear the free radical, in order to reduce the injury of brain tissue.
3. Innovation of the research
3.1It is the first time to study the mechanisms of signal transduction pathway of TMP intervening in ischemic stroke.
It confirmed that the pathways of TMP intervening in ischemic stroke are JNK/AP-1and Nrf2/ARE pathway in inflammation and oxidative stress-mediated signal transduction.
3.2This study observed the effects of TMP focus on MDA, NO, Catalase and GPx role of damaged cortical tissue of ischemic stroke in rats with injury of oxidative stress as a target. It determined that TMP can reduce peroxidation caused by permanent brain ischemia.
3.3This study focused on the effects of TMP on damaged cortical tissue immune cells of permanent ischemic stroke in rat (neutrophils, T lymphocytes, macrophages/microglia) and inflammatory cytokines (TNF-α, IL-1β, MPO, etc.) with inflammatory response of ischemic stroke as a target.
It confirmed that TMP anti-inflammatory effect is by down-regulating immune cells and inflammatory cytokines way.
引文
[1]赵建国主编.脑梗死[M].第2版.北京：人民卫生出版社,2012
[2]陈灏珠主编.实用内科学[M].第11版.北京：人民卫生出版社,2001
[3]李华德,颜国平.地塞米松联合甘露醇应用于急性重症脑血管病脑保护作用的临床研究[J].中国医学创新,2014,11(2)：31-33.
[4]封菲,丁美萍.创伤性脑水肿的发生机制及研究进展[J].心脑血管病防治,2013,13(6)：472-474.
[5]李军,曾邦雄.脑缺血损伤级联反应的研究进展[J].国外医学(麻醉学与复苏分册),2001,22(6)：364-368.
[6]甘照濡,桑栋楠.脑缺血再灌注损伤级联反应研究进展[J].医学综述,2009,15(1)：43-45.
[7]李传云,李伟华.脑缺血再灌注损伤机制的现代研究进展[J].中华现代中西医杂志,2005,3：1744-1746
[8]于炳新,吕传真.脑缺血半暗带研究进展[J].中国临床神经科学,2002,(10)：96-99.
[9]Racay P, Tatarkova Z, ChomovaM,et al. Mitochondrial calciumtransport and mitochondrial dysfunction after global brain ischemiain rat hippocampus[J].Neurochem Res,2009,34(8):1469-1478.。
[10]Zhang W, Petrovic JM, Callaghan D, et al. Evidence that hypoxia-in-ducible factor-1 (HIF-1) mediates transcriptional activation of interleukin-lbeta(IL-1 beta) in astrocyte cultures[J]. J Neuroimmuno,2006,174(12):63-73.
[11]Ichas F, Mazat JP. From Calcium signaling to cell death:two conformations for the mitochondrial permeability transition pore. Switching from low to high conductance state [J]. Biochim Biophys Acta,1998,1366(1-2):33-50.
[12]Brookes S, Yoon Y, Robotham JL, et al. Calcium ATP and ROS:a mitochondrial love-hate triangle [J]. Am J Physiol Cell Physio,2004,287(4): C817-C833.
[13]杨惠玲,潘景轩,吴伟康.高级病理生理学[M].第2版.北京：科学出版社,2006：27-31.
[14]Harukuni I, Bhardwaj A. Mechanisms of brain injuryafter global cerebral ischemia[J]. Neurol Clin,2006,24(1):1-21.
[15]淘录岭,刘轲.中药单体对脑缺血再灌注损伤保护的实验研究进展[J].时珍国医国药,2012,23(12)：3107-3109.
[16]李国彰主编.神经生理学[M].北京：人民卫生出版社,2007,149-151.
[17]Sen CK, Packer L. Antioxidant and redox regulation of gene transcription[J]. FASEB J,1996,10(7):709-720.
[18]Zhong LT, Sarafian T, kane DJ, et al. Bcl-2 inhibits deathof central neural cells induced by multiple agents[J]. Prcc Natl Acad Sci U S A,1993,90 (10):4533-4537.
[19]Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death[J]. Cell, 1993,(74):609-619.
[20]洪浩,刘国卿.缺血性脑血管疾病治疗的抗氧化应激策略[J].中国药理学通报,2004,(20)：19-24.
[21]陈念航.脑内一氧化氮与脑缺血损伤[J].国外医学生理、病理科学与临床分册,1995,15(4)：244-247.
[22]刘巍,王钜.一氧化氮,一氧化氮合成酶及其抑制剂在缺血性脑损伤研究中的进展[J].实验动物科学与管理,2006,23(3)：43-46.
[23]Mun CH, Lee WT, Park KA, et al. Regulation of endotheial nitric oxide synthase by agmatine after transient globalcerebral ischemia in rat brain [J].Anat Cell Biol,2010,43 (3):230-240.
[24]连瑜,李泽宇,张国华.一氧化氮及其合成酶在脑缺血中的作用[J].中国药物临床,2007,7(10)：779-780.
[25]齐聪儒,孔祥玉.中药对脑缺血再灌注损伤保护作用的研究进展[J].承德医学院学报,2008,25(4)：416-418.
[26]Zaleska MM, Mercado ML, Chavez J, et al. The development of stroket herapeutics:promising mechanisms and translational challenges [J]. Neuro-pharmacology,2009,56 (2):329-341.
[27]Khan M, Elango C, Ansari MA, et al. Caffeic acid phenethylester reduces neurovascular inflammation and protects rat brain following transient focal cerebral ischemia[J]. Neurochem,2007,102 (2):365-377.
[28]张昆南,曹金娟,刘世民,等.大鼠脑梗死后脑组织TNF-α、GFAP、NSE、 BDNF、Nestin的表达和神经功能变化[J].中国神经免疫学和神经病学杂志,2013(5)：305-310
[29]Wang Q, Tang XN, Midori A. The inflammatory responseins troke[J]. Neuro-immunol,2007,184 (1-2):53-68.
[30]Williams AJ, Dave J R, Tortella FC. Neuroprotection with the proteasome inhibitor MLN 519 in focal ischemic brain injury:Relation to nuclear factorkcB (NF2κB), inflammatory gene expression, and leukocyte infiltration[J] Neurochem Int,2006,49 (2):106-112.
[31]Minghetti L, Levi G. Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide.Prog[J]. Neurobiol.1998.54(1):99-125.
[32]Huang J, Upadhyay UM, Tamargo RJ. Inflammation in stroke and focal cerebral ischemia[J]. Surg Neurol,2006,66 (3):232-245.
[33]Pantoni L, Sarti C, Inzitari D. Cytokines and cell adhesion molecules in cerebral ischemia experimental bases and therapeutic perspective [J]. Arterioscler Thromb Vasc Biol,1998,18 (4):503-513.
[34]Wen YD, Zhang HL, Qin ZH. Inflammatory mechanism in ischemic neuronal injury[J]. Neurosci Bull,2006,22 (3):171-182.
[35]Ekdahl CT, Kokaia Z, Lindvall O. Brain inflammation and adult neurogenesis: The dual role of microglia [J]. Neuroscience,2009,158 (3):1021-1029.
[36]Yu AC, Lau L T. Expression of interleukin-1 alpha, tumor necrosis factor alpha and interleukin-6 genes in ast rocytes under ischemic injury[J]. Neurochem Int, 2000,36 (4-5):369-377.
[37]Gabriel C, J usticia C, Camins A, et al. Activation of nuclear factor-κB in the rat brain after transient focal ischemia[J]. Brain Res Mol Brain Res,1999,65 (1):61-69.
[38]Wen YD, Zhang HL, Qin ZH. Inflammatory mechanism in ischemic neuronal injury[J]. Neurosci Bull,2006,22 (3):171-182.
[39]Kato H, Takahashi A, Itoyama Y. Cell cycle protein expression in proliferating microglia and astrocytes following transient global cerebral ischemia in the rat [J]. Brain Res Bull,2003,60 (3):215-221.
[40]Arumugam TV, Woodruff TM, Lat hia JD, et al. Neuroprotection in stroke by complement inhibition and immunoglobulin therapy [J]. Neuroscience,2009, 158 (3):1074-1089.
[41]Ekdahl CT, Kokaia Z, Lindvall O. Brain inflammation and adult neurogenesis: The dual role of microglia [J]. Neuroscience,2009,158 (3):1021-1029.
[42]Liu B, Gao HM, Wang JY, et al. Role of nitric oxide ininflammation-mediated neurodegeneration[J]. Ann NYAcad Sci,2002,962:318-331.
[43]Kimura Y, Matsushita N, Okuda H. Effects of baicalein isolated from Scutellaria baicalensis on interleukin β- and tumor necrosis factor a-induced adhesion molecule expression in cultured human umbilical vein endothelial cells [J]. J Ethnopharmacol,1997,57(1):63-67.
[44]睢燕,周名雄.脑缺血再灌注损伤中炎症反应的免疫学机制[J].解剖与临床,2007,12(6)：436-438.
[45]Yamasaki Y, Matsuura N, Shozuhara H, et al. Interleukin-1 as pathogenetic mediator of ischemic brain damage in rats[J]. Stroke,1995; 26:676-680.
[46]Davies CA, Loddick SA, Toulmond S. The progression and topographic distribution of interleukin-1 beta expression after permanent middle cerebral artery occlusion in the rat[J]. J Cereb Blood Flow Metab,1999,19(1):87-98.
[47]Stover JF, Sakowitz OW, Schoning B, et al. Norepinephrine infusion increases interleukin-6 in plasma and cerebrospinal fluid of braininjured rats[J]. Med Sci Monit,2003,9(10):382-388.
[48]Morganti-Kossmann MC, Rancan M, Stahel PF, et al. Inflammatory response in acute traumatic brain injury:a double-edged sword[J]. Curr Opin Crit Care,2002, 8(2):101-105.
[49]Kovanen PT, KaartinenM, Paavonen T. Infiltrates of activated mast cells at the site of coronary atheromatous erosion or rupture in myocardial infarction[J]. Circulation,1995,92(5):1084-1088
[50]Clark WM, Rinker L G, LessovNS, et al. Lack of interleukin-6 expression is not protective against focal central nervous system ischemia[J]. Stroke,2000,31 (7):1715-1720.
[51]向赟,董大翠,刘庆莹.脑缺血与白细胞介素-6的变化[J].江汉大学学报(自然科学版),2005,23(2)：83-87.
[52]张国良血塞通对急性脑梗死患者血清TNF-α、IL-1β和IL-6浓度影响的临床研究[J].心脑血管病防治,2011,11(5)：378-380.
[53]Huang J, Upadhyay UM, Tamargo RJ. Inflammation in stroke and focal cerebral ischemia[J]. Surg Neurol,2006,66 (3):232-245.
[54]肖岚,黎杏群.白介素-6与脑缺血损伤[J].国外医学(神经病学神经外科学分册),2000,27(5)：258-261.
[55]Campbell IL, Erta M, Lim SL, et al. Trans-signaling is a dominant mechanism for the pathogenic actions of interleukin-6 in the brain[J]. J Neurosci,2014,34 (7):2503-2513.
[56]杨爱华,薛会光,初开秋,等.血清C反应蛋白与白介素-6检测及其与脑梗死相关关系探讨[J].现代预防医学,2008,35(21)：4291-4292.
[57]金美兰,杨桂芝.血浆白介素-8与急性脑梗死的相关性探讨中国医学创新[J].2012,(14)：56-57
[58]叶飞,罗建勤,陈建,等.血清NSE、IL-6和IL-8水平与急性脑梗死的关系[J].浙江实用医学,2012,(3)：192-193.
[59]Malisan F, Briere F, Bridon JM, et al. Interleukin-10 induces immunoglobulin G isotype switch recombination in human CD40-activated naive B lymphocytes[J]. J Exp Med,1996, (183):937-947..
[60]周婷,丁美萍,闻树群.急性脑梗死患者血清脂联素与IL-10的关系及意义[J].心脑血管病防治,2010,10(1)：17-19.
[61]Sairanen T, Carpen O, Karjalainen-Lindsberg ML, et al. Evolution of cerebral tumor necrosis factor-alpha production during human ischemic stroke[J]. Stroke, 2001,32 (8):1750-1758.
[62]Intiso D, Zarrelli MM, Lagioia G, et al. Tumor necrosis factor alpha serum levels and inflammatory response in acute ischemic st rokepatients[J]. Neurol Sci,2004, 24 (6):390-396.
[63]张明义,韩俊英,张蕴,等.血清肿瘤坏死因子-α对急性缺血性脑卒中患者预后的影响[J].中国现代神经疾病杂志,2007,7(3)：234-237.
[64]李沙,黄艳秋,游红琴,等.脑缺血再灌注损伤模型大鼠炎性反应相关信号研究[J].中国神经免疫学和神经病学杂志,2012,(6)：453-461.
[65]张莉莉,王景周,周华东,等.肿瘤坏死因子-α在大鼠脑缺血再灌注损伤中的作用机制[J].中华老年医学杂志,2003,22(2)：37-39
[66]Guo RB, Wang GF, Zhao AP, et al.Paeoniflorin protects against ischemia-induced brain damages in rats via inhibiting MAPKs/NF-κB-mediated inflammatory responses[J].PLoS One,2012,7(11):e49701.
[67]Zhang XM, Zheng XY, Sharkawi SS,et al. Possible protecting role of TNF-α in kainic acid-induced neurotoxicity via down-regulation of NFκB signaling pathway[J].Curr Alzheimer Res,2013,10(6):660-669.
[68]Guo RB, Wang GF, Zhao AP, et al. Paeoniflorin protects against ischemia-induced brain damages in rats via inhibiting MAPKs/NF-κB-mediated inflammatory responses[J]. PLoS One,2012,7(11):e49701.
[69]王晓平,罗永杰,马思文,等.Bcl-2,半胱氨酸-天冬氨酸蛋白酶在SD大鼠脑梗死急性期的动态表达研究实用医院临床杂志[J].2013,10(5)：53-56,57.
[70]施勤,刘继明.细胞的线粒体调控与Bcl-2基因家族[J].上海免疫学杂志,2000,20(1)：59-61.
[71]Niizuma K, Yoshioks H, Chen H, et al. Mitochondrial and apoptotic neuronal death signaling pathways in cerebral ischemia[J]. Biochim Biophy Acta,2010, 1802(1):92-99.
[72]Qiao H, Dong L, Protective effect of luteolin in experimental ischemic stroke: upregulated SOD1, CAT, Bcl-2 and claudin-5, down-regulated MDA and Bax expression[J]. Neurochem Res,2012,37(9):2014-2024.
[73]牟芳芳,于永娟.银杏叶提取物EGb761对大鼠脑缺血再灌注后细胞凋亡及Bcl-2,Bax蛋白表达的影响[J].上海中医药大学学报,2012,26(3)：78-81.
[74]支文煜.脑缺血再灌注损伤引起的线粒体功能障碍及丹参酮IIA的保护作用研究[J].实用心脑肺血管病杂,2010,18(10)：1389-1391.
[75]张予阳,史琳琳,郝冬海,等.Bcl-2在缺血性神经细胞损伤中的作用及药物的影响[J].中国药理学通报,2010,26(1)：21-24.
[76]徐开屏,孙风艳.线粒体释放的促凋亡蛋白和细胞凋亡[J].中国神经科学杂志,2002,18(4)：732-735.
[77]Haddad JJ. The role of Bax/Bcl-2 and procaspase peptides in hypoxia/ reperfusion-dependent regulation of MAPK (ERK):Discordant proteomic effect of MAPK (p38) [J]. Protein Pept Lett,2007,14(4):361-371.
[78]Gill MB, Bockhorst K, Narayana P, et al. Bax shuttling after neonatal hypoxia schemia:hyperoxia effects[J]. J Neurosci Res,2008,86(16):3584-3604.
[79]Schemdt-kastner R, Teuettner J, Zhao W, et al. Differential changes of bax, caspase-3, and p21 mRNA expression after transient focal brain ischemia in the rats[J]. Brain Res Mol Brain Res,2000,79(1-2):88-101.
[80]Zhao H, Yenari MA, Cheng D, et al. Bcl-2 over expression protects against neuron loss within the ischemia margin following experimental stroke and inhibits cytochrome C translocation and caspase-3 activity [J]. Neurochem, 2003,85(4):1026-1036
[81]Cheng CY, Su SY, Tang NY, et al. Ferulic acid inhibits nitric oxide-induced apoptosis by enhancing gaba (b1) receptor expression intransient focal cerebral ischemia in rats[J]. Acta Pharmacol Sin,2010,31(8):889-899.
[82]Broughton BR, Reutens DC, Sobey CG Apoptotic mechanisms after cerebral ischemia[J]. Stroke,2009,40(5):e331-339.
[83]Brunelle JK, Letai A. Control of mitochondrial apoptosis by the Bcl-2 family [J]. J Cell Sci,2009,122(4):437-444.
[84]Mehta S L, Manhas N, Raghubir R. Molecular targets in cerebral ischemia for developing novel therapeutics[J]. Brain Res Rev,2007,54(1):34-66.
[85]Karatas H, Aktas Y, Ozdemir Y, et al. A nanomedicine transports a peptide caspase-3 inhibitor across the blood-brain barrier and provides neuroprotection [J]. J Neurosci,2009,29(44):13761-13769
[86]刘广义.脑缺血后Caspase-3蛋白Bcl-2和Bax基因表达在神经损伤中的作用[J].中国康复,2010,25(3)：163-166.
[87]陈月桥,王丽,武建华.细胞凋亡信号传导途径研究进展[J].中国实用医药,2007,2(33)：186-187.
[88]王爱莲,李懿萍.线粒体和凋亡[J].国外医学(临床生物化学与检验分册),2000,21(6):287-288
[89]Blomgran R, Zheng L, Stendahl O. Cathepsin-cleaved Bid promotes apoptosis in human neutrophils via oxidative stress-induced lysosomal membrane permeabilization [J]. J Leukoc Biol,2007,81(5):1213-1223.
[90]Ho PK, Hawkins CJ.Mammalian initiator apoptotic caspases[J].FEBS J,2005, 272 (21):5436-5453.
[91]Gu Qing, Wang Ji-de, Harry HX, et al. Activation of the caspase-8/Bid and Bax pathways in aspirin-induced apoptosisin gastric cancer [J].Carcino-genesis, 2005,26(3):541-546.
[92]庞涛,陈婉蓉.线粒体与细胞凋亡的研究进展[J].卫生毒理学杂志,2003,6(17)：122-124.
[93]Liu B, Gao HM, Wang JY, et al. Role of nitric oxide ininflammation-mediated neurodegeneration[J]. Ann NY Acad Sci,2002, (962):318-331.
[94]Boehning D, Patterson RL, Sedaghat L, et al. Cytochrome c binds alto inositol (1,4,5)trisphosphate receptors, amplifying calcium-dependent apoptosis[J]. Nat Cell Biol,2003,5(12):1051-1061.
[95]Boehning D, van Roswm DB, Patterson RL, et al. A peptide inhibitor of cytochrome c/ inositol 1,4,5 trisphosphate receptor binding blocks intrinsic and extrinsic cell death pathways[J]. Proc Natl Acad Sci USA,2005,102 (5):1466-1471.
[96]Chaudhry P, Srinivasan R, Patel FD, et al. Serum soluble Fas levels and prediction of response to platinum-based chemotherapy in epithelial ovaria cancer [J]. Int J Cancer,2008,122(8):1716-1721.
[97]Villa-Morales M, Santos J, Prez-Gmez E, et al. A role for the Fas/FasL system in modulating genetic susceptibility to T-cell lymphoblastic lymphomas[J]. Cancer Res,2007,67(11):5107-5116.
[98]Tephly LA,CarterAB. Differential expression and oxidation of MKP-1 modulates TNF alpha gene expression[J]. Am J Respir Cell Mol Biol,2007,37(3):366-374.
[99]Higuchi Y, Chan TO, Brown MA, et al. Cardioprotection afforded by NF-kappa B ablation is associated with activation of Akt in mice overexpressing TNF-alpha [J]. Am J Heart Circ Physiol,2006,290(2):H590-H598.
[100]蒋杞英,王志新,大鼠局灶性脑缺血再灌注脑组织神经细胞凋亡与Bcl-2, Bcl-x1蛋白检测[J].郑州大学学报(医学版),2004,3(9)：428-431.
[101]赵航,王敏.缺血再灌注大鼠脑皮质Bcl-2、Bax和Caspase-3的动态表达[J].中国老年医学杂志,2012,7(13)：2801-280.
[1]黄启福,王谦主编.病理学[M].第3版.北京：科学出版社,2013,11-20.
[2]李桂源主编.病理生理学[M].第2版.北京：人民卫生出版社,2013,248-261.
[3]金惠铭主编.病理生理学[M].第8版.北京：人民卫生出版社,2013,129-136.
[4]鞠躬主编.神经生物学[M].北京：人民卫生出版社,2004,159-181.
[5]黄文林,朱孝峰主编.信号转导[M].北京：人民卫生出版社,2005,1-11.
[6]刘景生主编.细胞信息与调控[M].第2版.北京：中国协和医科大学出版社,2004,185-255
[7]卢建等主编.受体信号转导系统与疾病[M].济南：山东科学技术出版社,2002,34-420.
[8]金伯泉主编.细胞和分子免疫学[M].北京：科学出版社,2003,1-39
[9]Brea D, Sobrino T, Ramos-Cabrer P, et al. Inflammator and neuroimmuno-modulatory changes in acute cerebral ischemia[J]. Cerebrovasc Dis,2009, 27(Suppll):48-64.
[10]吴克复.细胞通讯与疾病.北京：科学出版社,2006,216-223,242-264.
[11]Rosenzweig HL, Minami M, Lessov NS, et al. Endotoxin preconditioning protects against the cytotoxic effects of TNF-alpha after stroke:a novel role for TNF-alpha in LPS-ischemic tolerance[J]. Cereb Blood Flow Metab,2007,27 (10):1663-1674.
[12]Akira S, Uematsu S, Takcuchi O. Pathogen recognition and innate immunity [J]. Cell,2006,124(4):783-801.
[13]李丽燕.Toll样受体的研究进展[J].临床医学工程,2011,18(3)：467-469.
[14]王德成,余敏,余锐萍,等.Toll样受体研究进展[J].动物医学进展,2008,29(2)：56-60.
[15]Uematsu S, Akira S. Toll-like receptors and type I interferons [J]. Journal of biological chemistry,2007,282(5):15319-15324.
[16]Kaisho T, Akira S. Toll-like receptor function and signaling[J]. Allergy Clinimmunol,2006,117(5):979-987.
[17]Hyakkoku K, Hamanaka J, Tsuruma K, et al. Toll-like receptor 4(TLR4), but not TLR3 or TLR9, knockout mice have neuroprotective effects against focal cerebral ischemia[J]. Neuroscience,2010,171(1):258-267.
[18]Tang SC, Arumugam TV, Xu X, et al. Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits[J]. Proc Natl Acad Sci USA,2007, 104(34):13798-13803.
[19]Ziegler G, Harhausen D, Schepers C, et al. TLR2 has a detrimental role in mouse transient focal cerebral ischemia[J]. Biochem Biophys Res Commun,2007, 359(3):574-579.
[20]孙鹏,张清,韩继媛,等.体外模拟脑缺血再灌注条件下BV-2细胞TLR4信号途径对TLR2表达的影响中国科学(C辑),2009,(11)：1013-1018.
[21]Wang YC, Lin S, Yang QW. Toll-like receptors in cerebral ischemic inflammatory injury[J]. Journal of Neuroinflammation,2011,8(1):134-144.
[22]Cao CX, Yang QW, LV FL, et al. Reduced cerebral ischemia-reperfusion injury in Toll-like receptor 4 deficient mice[J]. Biochem Biophys Res Commun,2007, 353(2):509-514.
[23]张清,孙鹏,冯新民,等.Toll样受体4在大鼠脑缺血再灌注损伤中的表达及其意义[J].华中科技大学学报(医学版),2008,37(2)：219-221.
[24]李国彰.神经生理学[M].人民卫生出版社,2007：115-116.
[25]姜勇.LPS介导细胞激活的信号转导：从CD14到p38MAPK通路的研究[J].生理科学进展,1999,30(1)：29-34.
[26]Hu BR, Liu CL, Park DJ. Alteration of MAP kinase pathways after transient forebrain ischemia [J]. J Cereb Blood Flow Metab,2000,20(7):1089-1095.
[27]Raingeaud J, Gupta S, Rogers JS, et al. Pro-inflammatory cytokines and environmental stress cause p38 mitogen activated protein kinase activation by dual phosphory lation on tyrosine and threonine [J]. J Biol Chem,1995,270(13): 7420-7426.
[28]Lee JC, Laydon JT, Mc Donnell PC, et al. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis [J]. Nature,1994,372 (6508):739-746.
[29]Nijboer CH, van der Kooij, MA, van Bel F, et al.Inhibition of the JNK/AP-1 pathway reduces neuronal death and improves behavioral outcome after neonatal hypoxic-ischemic brain injury[J]. Brain Behavior Immun,2010,24(5):812-821.
[30]Tanaka S, Masuda Y, Honma C, et al. Manganese promotes phorbol esterinduced interleukin-2 production via AP-1 activation in Jurkat T-cells[J]. Toxicol Lett, 2012,211(3):312-318.
[31]Chen YR, Tan TH. The c-Jun N-terminal kinase pathway and apoptotic signaling (review) [J]. Int J Oncol,2000,16(4):651-62.
[32]黎增辉,廖爱军.JNK信号通路[J].国际病理科学与临床杂志,2010,30(3)：273-276.
[33]Sabapathy K. Role of the JNK pathway in human diseases [J]. Prog Mol Biol Transl Sci,2012, (106):145-169.
[34]MoriY, GotohY. Role of the JNK signaling pathway[J]. Tanpakushitsu Kakusan Koso,2008,53(10):1252-1257.
[35]李欣,魏红艳,胡春林,等.SAPK/JNK信号通路在脑梗死后神经元凋亡中的作用[J].中国病理生理杂志,2011,(8)：1552-1556.
[36]Kaminska B, Gozdz A, Zawadzka M, et al. MAPK signal transduction underlying brain inflammation and gliosis as therapeutic target. Anat Rec (Hoboken) [J].2009,292(12):1902-1913.
[37]Jawien J, Gajda M, Mateuszuk L, et al. Inhibition of Nuclear factor-JB attenuates atherosclerosis in apoE/LDLR-Double knockout mice [J]. Physiol Pharmacol, 2005,56(3):483-489.
[38]Brasier AR. The NF-kappaB regulatory network [J]. Cardiovasc Toxicol,2006, 6(2):111-130.
[39]Brevetti G, Schiano V, Chiariello M. et al. Cellular adhesion molecules and peripheral arterial disease [J]. Vase Med,2006, 11(1):39-47.
[40]Nijboer CH, Heijnen CJ, Groenendaal F, et al. A dual role of the NF-kappa B pathway in neonatal hypoxic-ischem ic brain damage[J]. Stroke,2008,39(9): 2578-2586.
[41]甘露,袁萱,张红,等.Nrf2/Keap1抗氧化系统与缺血性脑病[J].农垦医学,2011,33(1)：79-82.
[42]朱凤臣,蒋电明.Nrf2/ARE转导通路在中枢神经系统疾病中作用的研究进展[J].中国生物制品学杂志,2011,24(6)：741-744.
[43]Shih AY, Johnson DA, Wong G, et al. Coordinateregulation of glutathione biosynthesis and release by Nrf2-expressing gliapotently protects neurons from oxidative stress[J]. J Neurosci,2003,23(8):3394-3406.
[44]Li W, Jain MR, Chen C, et al. Nrf2 Possesses a redoxin sensitive nuclear export signal overlapping with the leucine zipper motif[J]. BioChem,2005,280(31): 28430-28438.
[45]童海达,王佳茗,宋英. Keapl-Nrf2-ARE在机体氧化应激损伤中的防御作用[J].癌变,畸变,突变,2013,25(1)：71-75.
[46]Kobayashi A, Ohta T, Yamamoto M. Unique function of the Nrf2-Keapl pathway in the inducible expression of antioxidant and detoxifying enzymes [J]. Methods Enzymol,2004, (378):273-286.
[47]Kraft AD, Lee JM, Johnson DA, et al. Neuronal sensitivityto kainic acid is dependent on the Nrf2-mediated actions of the antioxidant response element[J]. Journal of Neurochemistry,2006,98(6):1852-1865.
[48]Jeong WS, Keum YS, Chen C, et al. Differential expression and stability of endogenous nuclear factor E2-related factor 2 (Nrf2) by natural chemo-preventive compounds in HepG2 human hepatoma cells[J]. J Biochem Mol Biol, 2005,38(2):167-176.
[49]钟敏Nrf2-Keap1抗氧化系统研究进展[J].中国公共卫生,2006,22(3)：360-362.
[50]Kraft AD, Johnson DA, Johnson JA. Nuclear factor E2-related factor 2-dependent antioxidant response element activation by tertbutylhydroquinone and sulforaphane occurring preferentially in astrocytes conditions neurons against oxidative insult[J]. J Neurosci,2004,24(5):1101-1112.
[1]张琦,叶夷露,颜吟雪,等.黄连解毒汤对小鼠脑缺血慢性神经损伤的保护作用[J].浙江大学学报(医学版),2009,38(1)：75-80.
[2]刘斌,蔡梅芝,李爱华,等.参芎化瘀胶囊对大鼠急性脑缺血再灌注损伤的保护作用[J].中国实验方剂学杂志,2012,18(11)：229-232.
[3]刘敬霞,李建生,俞维.星萎承气汤和补阳还五汤对脑缺血大鼠海马神经元损伤的影响[J].中国实验方剂学杂志,2012,18(12)：233-237.
[4]唐红梅,白雪.中医药治疗缺血性脑卒中的优势探讨[J].中医药导报,2011,17(10)：90-92.
[5]王清任.医林改错[M].北京：人民军医出版社,2007.
[6]杨佳昕.王清任补阳还五汤治疗中风病文献研究[J].实用中医内科杂志,2012,26(11)：10-13.
[7]刘泰,黄德庆.补阳还五汤治疗急性缺血性中风随机对照试验的meta分析[J].辽宁中医杂志,2012,39(10)：1913-1915.
[8]徐谦,陈新林,沈耿.等.补阳还五汤干预中风先兆证的Meta分析[J].中国实验方剂学杂志,2013,19(16)：339-343.
[9]欧迎跃.补阳还五汤联合西医治疗急性脑梗死临床疗效观察[J].内蒙古中医药,2013,(3)：56-57.
[10]邵承玲.补阳还五汤加减治疗脑梗死恢复期的临床疗效分析[J].中国医药指南,2013,11(23)：273-274.
[11]刘永平.补阳还五汤在缺血性中风恢复期肢体麻木患者的应用[J].中国中医药现代远程教育,2013,11(9)：15-16.
[12]董征亮、陈永斌、姜薇.补阳还五汤及其加减方治疗脑梗死的临床研究进展[J].中国当代医药,2013,20(9)：24-27.
[13]周赛男,蔺晓源,易健,等.补阳还五汤对脑缺血大鼠神经功能及细胞形态的影响[J].中国实验方剂学杂志,2013,19(2)：251-254.
[14]杨春根.补阳还五汤对大鼠脑缺血再灌注损伤的保护作用[J].现代中药研究 与实践,2010,24(1)：36-39.
[15]柯锋,吴洪,邓春龄,等.补阳还五汤对气虚血瘀型和非气虚血瘀型缺血性中风病人的疗效比较[J].中西医结合心脑血管杂志,2005,(11)：962-964.
[16]杨虹,魏桂荣,李红戈.脑梗死血清MMP-3与MMP-9的动态变化及临床意义[J].中国康复,2005,20(5)：278-280.
[17]蓝艳.补阳还五汤对气虚血瘀型缺血性脑卒中患者血浆基质金属蛋白酶影响[J].福建中医药,2013,44(1)：21-22.
[18]许慧娜,陈光明.补阳还五汤对缺血性脑损害神经细胞凋亡影响的研究进展[J].现代中西医结合杂志,2011,20(12)：1551-1553.
[19]刘俊娥,张继平.补阳还五汤抗脑缺血神经细胞凋亡实验研究进展[J].中国中医药信息杂志,2011,18(9)：110-112.
[20]王新高,童萼塘,孙圣刚.补阳还五汤对脑缺血再灌注大鼠皮质神经细胞凋亡的影响[J].现代中西医结合杂志,2005,14(3)：306-309.
[21]曲宏达,佟丽,沈剑刚,等.补阳还五汤药物血清对体外培养大鼠皮层神经元缺氧后P53和P21表达的影响[J].中国中酉医结合杂志,2004,24(2)：133-135.
[22]廖春来,伶丽,陈育尧.补阳还五汤对大鼠脑缺血半暗区Caspase-3 mRNA表达的影响[J].中国临床康复,2004,8(19)：3821-3823.
[23]尹天雷,蔡光先,李勇敏,等.补阳还五汤对脑缺血模型大鼠脑组织NGF及PI3K/AKT信号转导途径的影响[J].中国中医药科技,2008,15(1)：24-25.
[24]Sun HJ, Li TM, Wang GX. Protective effect of Xuefuzhuyu Decoction for focal cerebral ischemia[J]. China Journal of Chinese Medicine,2013,28(7):981-983.
[25]雷燕,王军辉,李忠文.血府逐瘀汤组方配伍及加减运用的实验研究概述[J].中国实验方剂学杂志,2001,7(6)：57-59.
[26]李应宏.血府逐瘀汤治疗急性缺血性脑卒中的疗效[J].中国康复理沦与实践,2013,19(3)：263-265.
[27]孙寒静,黎同明,王桂香.血府逐瘀汤对大鼠局灶性脑缺血模型的保护作用[J].中医学报,2013,28(7)：981-983.
[28]王倬,王宁,王东披.血府逐瘀汤对缺血缺氧性脑损伤大鼠的保护作用[J]. 浙江中医杂志,2009,44(11)：793-795.
[29]Raner MS, Priestley JV, Ncmahon SB. Functional regeneration of sensory axons into the adult spinal cord [J]. Nature,2000,403(6767):312-316.
[30]Sofroniew MV, Howe CL, Mobley WC. Nerve growth factor signaling, neuroprotection, and neural repair[J]. Annu Rev Neurosci,2001,(24):1217-1281.
[31]Chiaretti A, Antonelli A, Mastrangelo A, et al. lnterleukin-6 and nerve growth factor upregulation correlates with improved outcome in children with severe traumatic brain injury [J]. J neurotrauma,2008,25(3):225-234.
[32]吕中,王宁,王东披.益气活血法对缺氧缺血性脑损伤保护作用的实验研究[J].中华中医药学刊,2011,29(7)：1552-1555.
[33]陶勇军,陈云志.《医林改错》方药临床运用[J].实用中医内科杂志,2011,25(6)：33-34.
[34]凌敬.通窍活血汤加减治疗急性脑梗死的疗效观察[J].世界中医药,2013,8(3)：303-305.
[35]吴苏宁.内皮素与缺血性脑血管疾病的治疗研究进展[J].国外医学老年医学分册,1999,20(3)：97-99.
[36]孙琳,李义召.降钙素基因相关肽与脑血管病[J].山东医药,2001,41(1)：58-60.
[37]汪宁,刘青云,彭代银,等.活血通窍汤对脑缺血大鼠脑组织中CGRP, ET, IL-1β,TNF-α的影响[J].中成药,2005,27(11)：1295-1297.
[38]汪宁,刘青云,彭代银,等.活血通窍汤对脑缺血大鼠的保护作用及机制研究[J].中国中医药信息杂志,2004,11(5)：407-409.
[39]崔英慧.活血通窍汤治疗短暂性脑缺血发作的疗效及对体内炎症反应的影响[J].现代中西医结合杂志,2012,21(23)：2572-2573.
[40]汪宁,许风清,邓奕,陈威,等.通窍活血汤对谷氨酸损伤PC 12细胞保护作用的实验研究[J].中国中医药科技,2008,15(2)：101-102.
[41]KaoTK, Liang SM. Pharmacological research and development of Tetramethyl-pyrazine in the role of cardiovascular and cerebrovascular[J]. SJT Tcm,2011, 5(2):58-68.
[42]王丽,吕圭源,陈素红.川芎嗪药理作用的研究进展[J].医学信息(上旬刊),2011,24(3)：1116-1118.
[43]马丽虹,李冬梅,李可建.川芎嗪注射液治疗缺血性脑卒中急性期临床疗效的系统评价[J].中国老年学杂志,2013,33(16)：3825-3827.
[44]孙建华.脑梗死患者脑循环动力学改变和川芎嗪对急性缺血性脑损伤的保护作用[J].中国中西医结合急救杂志,2005,12(4)：248-249.
[45]楚冰,邵国富,周旭平.川芎嗪对大鼠局灶性脑缺血后额叶、丘脑、小脑病理形态改变的影响[J].神经疾病与精神卫生,2004,(4)：250-251.
[46]甘照濡,桑栋楠.脑缺血再灌注损伤级联反应研究进展[J].医学综述,2009,15(1)：43-45.
[47]李建生,李建国,赵君玫等.川芎嗪和参麦注射液对老龄大鼠脑缺血再灌注多器官损伤的作用[J].国际中西医结合养生学与康复医学学术研讨会论文汇编[C].2000,251-257.
[48]邵国富,包仕尧.川芎嗪、丹参、丹皮酚和当归对脑缺血后再灌注期脑血流量的影响[J].中国中西医结合杂志,1998,(S1)：57-59,361.
[49]张景秋,赵喜庆,吉训明,等.川芎嗪对大鼠脑缺血再灌注损伤的作用[J].临床误诊误治,2012,24(2)：41-43.
[50]刘德山,朱爱华,陈克忠.川芎嗪注射液对脑缺血再灌注家兔体感诱发电位的影响[J].山东大学学报(医学版),2003,41(4)：405-407.
[51]张萌,邸东华,李盈.川芎嗪对大鼠脑缺血再灌注后线粒体功能的影响[J].辽宁中医药大学学报,2009,(2)：172-173.
[52]Acalovschi D, Wiest T, Hartmann M, et al. Multiple levels of regulation of the interleukin-6 system in stroke[J]. Stroke,2003,34(8):1864-1869.
[53]Khan M, Elango C, Ansari MA, et al. Caffeic acid phenethylesterreduces neurovascular inflammation and protects rat brain following transient focal cerebral ischemia[J]. J Neurochem,2007,102(2):365-377.
[54]Williams AJ, Dave J R, Tortella FC. Neuroprotection with the proteasome inhibitor MLN 519 in focal ischemic brain injury:Relation to nuclear factor κB (NF2κB), inflammatory gene expression, and leukocyte infiltration[J]. Neurochem Int,2006,49(2):106-112.
[55]Wang Q, Tang XN, Yenari MA. The inflammatory response instroke [J]. Neuroimmunol,2007,184(1-2):53-68.
[56]高长越,周华东,邓娟,等.川芎嗪对脑缺血再灌注损伤后细胞粘附作用的影响[J].中国临床康复,2006,(35)：178-179,192.
[57]李建民,陈长香,赵雅宁,等.川芎嗪对沙鼠前脑缺血-再灌注损伤后学习记忆的影响[J].河北医药,2010,32(1)：19-21.
[58]陆将,曹义战,仲月霞,等.川芎嗪对局灶性脑缺血后MPO活性及白细胞介素-6含量的影响[J].中国中医急症,2008,17(4)：508-509.
[59]陈龙,王文华,朱胜强,等.川芎嗪对大鼠脑缺血再灌注后1L-1β和ICAM-1表达的影响[J].临床医药实践,2009,18(8)：561-562.
[60]孙寒静,郑缅华,梁天山.川芎嗪注射液对急性脑梗死患者血清sCD40L及hsCRP水平的影响[J].上海中医药大学学报,2013,27(4)：39-41.
[61]Dominique TV, Renaud T, Xavier W, et al. Isoflurane inhaled at the onset of reperfusion potentiates the cardoprotective effect of ischemic postconditioning through a NO-dependent mechanisn [J]. J Cardliovasc Pharmacol,2006,47(3): 487-492.
[62]丁兴.盐酸川芎嗪抗大鼠脑缺血再灌注损伤的实验研究[J].甘肃中医,2008,21(9)：58-59.
[63]阮琴.川芎挥发油川芎嗪对小鼠脑缺血再灌注损伤的保护作用[J].浙江中医杂志.2009,44(9)：642-643.
[64]徐芝秀.川芎嗪对大鼠脑缺血再灌注损伤的保护作用[J].实用中医药杂志,2007,23(7)：411-413.
[65]张春兵,丁兴,詹臻.盐酸川芎嗪对大鼠脑缺血再灌注损伤的保护作用[J].江苏中医药,2008,40(4)：77-79.
[66]祁存芳,张建水,田玉梅,等.川芎嗪对成年大鼠脑缺血再灌注损伤后nNOS的表达和神经的影响[J].南方医科大学学报,2007,27(6)：771-774.
[67]Kinderlerer A R, Pombo Gregoire I, Hamdulay S S, et al. Heme oxygenase-1 expression enhances vascular endothelial resistance to complement-mediated injury through induction of decay-accelerating factor:a role for increased bilirubin and ferritin[J]. Blood,2009,113(7):1598-1607.
[68]冯海松,黎红华.川芎嗪注射液对急性脑梗死患者的抗氧化保护作用[J].河南中医,2013,33(9)：1466-1467.
[69]Brittain T, Skommer J, Raychaudhuri S, et al. An antiapoptotic neuroprotective role for neurologic[J]. Int J Mol Sci,2010,11 (6):2306-2321.
[70]MartinLJ, Price AC, Mcclendon KB, et al. Early events of target deprivation axotomy-induced neuronal apoptosis in vivo:oxidative stress, DNA damage, p53 phosphorylation and subcellular redistribution of death proteins[J]. J Neurochem,2003,85(1):234-247.
[71]Doyle KP, Simon RP, Stenzel-Poore MP. Mechanisms of ischemic brain damage [J].Neuropharmacology,2008,55(3):310-318.
[72]Tabira T. Singificance of intracellular a beta in Alzheimer's disease[J]. Nihon Shinkei Seishin Yakurigaku Zasshi,2002,22(5):175-180.
[73]Nakatsuka H, Ohta S, Tanaka J, et al. Cytochrome C release from mitochondria to the cytosol was suppressed in the ischemia-tolerance-induced hippocampal CA1 region after 5-min forebrain ischemia in gerbils[J]. Neurosci Lett,2000, 278(1-2):53-56.
[74]吕少平,孙锋,王春霞.川芎嗪对脑缺血再灌注时细胞凋亡的影响[J].河北医学,2000,6(8)：673-675.
[75]王世龙,林原,唐泽耀.川芎嗪在各类神经系统损伤中的保护作用及其机制研究进展[J].中国药理学通报,2010,26(4)：438-442.
[76]张辉,牛书雷,王发亮,等.脑缺血再灌注大鼠额叶皮质内Bcl-2和HSP70的表达及川芎嗪,尼莫地平的干预作用[J].神经解剖学杂志,2009,25(1)：79-83.
[77]李庚华,杨迎春,任占川.川芎嗪对大鼠脑缺血再灌注损伤后大脑皮质Bcl-2表达的影响[J].解剖学杂志,2010,33(1)：82-85.
[78]柳朝阳,孙鹏,苗志,张涛,等.川芎嗪抑制大鼠局灶性脑缺血损伤神经元凋亡的作用[J].中国老年学杂志,2010,30(11)：1519-1521.
[79]张辉,牛书雷,王发亮,等.脑缺血再灌注大鼠额叶皮质内Bcl-2和HSP70的表达及川芎嗪,尼莫地平的干预作用[J].神经解剖学杂志,2009,25(1)： 79-83.
[80]Li M, Zhao MQ, Kumar Durairajan SS, et al. Protective effect of tetramethylpyrazine and salvianolic acid B on apoptosis of rat cerebral microvascular endothelial cell under high shear stress[J]. Clin Hemorheol Microcirc,2008,38(3):177-187.
[81]张晓丽,蒋丽娜,赵荧,等.川芎嗪对脑缺血再灌注后皮质Bax mRNA表达的影响[J].时珍国医国药,2008,19(9)：2109-2110.
[82]赵秋振,刘玉利,张辉,等.川芎嗪对大鼠脑缺血再灌注海马神经元BaxmRNA表达的影响[J].时珍国医国药,2011,22(2)：435-436.
[83]肖成云,刘军涛.川芎嗪对大鼠脑缺血再灌注Bcl-2、c-fos、Caspase-3的影响[J].河南中医学院学报,2007,22(4)：28-29.
[84]曲友直,高国栋,赵振伟,等.川芎嗪,黄芪对脑缺血再灌注后神经细胞凋亡及Fos蛋白表达的影响[J].卒中与神经疾病,2004,11(2)：111-112.
[85]吕少平,孙锋,王春霞.川芎嗪对脑缺血再灌注时细胞凋亡的影响[J].河北医学,,2000,6(8)：673-675.
[86]Xiao R, Qiao JT, Zhao HF, et al. Sodium selenite induces apoptosis in cultured cortical neurons with special concomitant changes in expression of the apoptosis-related genes[J]. Neurotoxicology,2006,27(4):478-484.
[87]季旭明,车萍,齐东梅,等.川芎嗪干预大鼠局灶性脑缺血模型神经元细胞凋亡的作用机制研究[J].中华中医药学刊,2012,30(11)：2461-2464.
[88]Kao TK, Ou YC, Kuo JS, et al. Neuroprotection by tetramethylpyrazine against ischemic brain injury in rats[J]. Neurochem Int,2006,48(3):166-176.
[1]李传云,李伟华.脑缺血再灌注损伤机制的现代研究进展[J].中华现代中西医杂志,2005,3(19)：1744-1746.
[2]戴甲培,冯斌.治疗急性缺血性脑中风神经保护药物研发的进展和展望[J].2012,31(2)：50-55.
[3]唐红梅,白雪.中医药治疗缺血性脑卒中的优势探讨[J].中医药导报,2011,17(10)：90-92
[4]欧迎跃.补阳还五汤联合西医治疗急性脑梗死临床疗效观察[J].内蒙古中医药,2013,(3)：56-57.
[5]邵承玲.补阳还五汤加减治疗脑梗死恢复期的临床疗效分析[J].中国医药指南,2013,11(23)：273-274.
[6]董征亮,陈永斌,姜薇.补阳还五汤及其加减方治疗脑梗死的临床研究进展[J].中国当代医药,2013,20(9)：24-27.
[7]周赛男,蔺晓源,易健,等.补阳还五汤对脑缺血大鼠神经功能及细胞形态的影响[J].中国实验方剂学杂志,2013,19(2)：251-254.
[8]杨春根.补阳还五汤对大鼠脑缺血再灌注损伤的保护作用[J].现代中药研究与实践,2010,24(1)：36-39.
[9]马丽虹,李冬梅,李可建.川芎嗪注射液治疗缺血性脑卒中急性期临床疗效的系统评价[J].中国老年学杂志,2013,33(16)：3825-3827.
[10]张景秋,赵喜庆,吉训明,等.川芎嗪对大鼠脑缺血再灌注损伤的作用[J].临床误诊误治,2012,24(2)：41-43.
[11]阮琴.川芎挥发油川芎嗪对小鼠脑缺血再灌注损伤的保护作用[J].浙江中医杂志,2009,44(9)：642-643.
[12]丁兴.盐酸川芎嗪抗大鼠脑缺血再灌注损伤的实验研究[J].甘肃中医,2008,21(9)：58-59.
[13]张春兵,丁兴,詹臻.盐酸川芎嗪对大鼠脑缺血再灌注损伤的保护作用[J].江苏中医药,2008,40(4)：77-79.
[14]徐芝秀.川芎嗪对大鼠脑缺血再灌注损伤的保护作用[J].实用中医药杂志,2007,23(7)：411-413.
[15]Kao TK, Ou YC, Kuo JS, et al. Neuroprotection by tetramethylpyrazine against ischemic brain injury in rats[J]. NeurochemInt,2006,48(3):166-176.
[16]Liao SL, Kao TK, Chen WY, et al. Tetramethylpyrazine reduces ischemic brain injury in rats[J]. Neurosci Lett,2004,372(1-2):40-45.
[17]Chen CJ, Cheng FC, Liao SL, et al. Effects of naloxone on lactate, pyruvate metabolism and antioxidant enzyme activity in rat cerebral ischemia/reper-fusion[J]. Neurosci Lett,2000,287(2):113-116.
[18]Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats [J]. Stroke,1989,20(1):84-89.
[19]屈会化,赵琰,卢建秋,等.缺血性中风动物模型研究现状[J].中国实验动物学报,2010,18(4)：94-97.
[20]Longa EZ, Weinstein PR, Carlson S, et al. Reversible middlecerebral artery occlusion without craniectomy in rats[J]. Stroke,1989,20(1):84-91.
[21]Chang CY, Kuan YH, Li JR, et al. Docosahexaenoic acid reduces cellular inflammatory response following permanent focal cerebral ischemia in rats[J]. J Nutr Biochem,2013,24 (12):2127-2137. (IF 4.552)
[22]Kao TK, Chang CY, Ou YC, et al. Tetramethylpyrazine reduces cellular inflammatory response following permanent focal cerebral ischemia in rats[J]. Exp Neurol,2013, (247):188-201. (IF 4.645)
[23]Wang YY, Chen CJ, Lin SY, et al. Hyperglycemia is associated with enhanced gluconeogenesis in a rat model of permanent cerebral ischemia[J]. Mol Cell Endocrinol,2013,367(1-2):50-56. (IF 4.039)
[24]Wang YY, Lin SY, Chuang YH, et al. Activation of hepatic inflammatory pathways via sympathetic system is associated with hepatic insulin resistance in male ischemic stroke rats[J]. Endocrinology (In Press) 2014, (IF4.717)
[25]Li F, Fisher M. Animal modeling for developing stroke therapy. In:Fisher M (Ed.) Stroke therapy[M]. Woburn, MA:Butterworth-Heinemann,2001, 83-96.
[26]Joshi CN, Jain SK, Murthy PS. An optimized triphenyltetrazolium chloride method for identification of cerebral infarcts[J]. Brain Res Brain Res Protoc 2004,13(1):11-17.
[27]Panickar KS, Qin B, Anderson RA. Ischemia-induced endothelial cell swelling and mitochondrial dysfunction are attenuated by cinnamtannin D1, green tea extract, and resveratrol in vitro[J]. Nutr Neurosci,2014, Epub ahead of print.
[28]Neumann-Haefelin T, Kastrup A, de Crespigny A, et al. Serial MRI after transient focal cerebral ischemia in rats:dynamics of tissue injury, blood-brain barrier damage, and edema formation[J]. Stroke,2000,31(8):1965-1972.
[29]Yang Y, Rosenberg GA. Blood-brain barrier breakdown in acute and chronic cerebrovascular disease[J]. Stroke,2011,42(11):3323-3328.
[30]Ueno M, Molecular anatomy of the brain endothelial barrier:an overview of the distributional feature[J]. Curr Med Chem.2007,14(11):1199-1206.
[31]李玉芳,刘坤,倪月秋,等.川芎嗪对大鼠脑缺血再灌注后血脑屏障的保护作用及Claudin-5表达的影响[J].中国医科大学学报,2013,4(6)：511-514.
[32]刘洋,刘敬霞,李娟,等.中医药调控脑缺血损伤血脑屏障通透性作用机制的研究进展[J].辽宁中医杂志,2013,40(10)：2160-2163.
[1]王文静,孙呈皓,戴敏超,等.氧化应激对脑缺血再灌注损伤后自噬调控机制[J].中国微侵袭神经外科杂志,2013,18(6)：275-279.
[2]王全伟,凡文博,王智昊,等.氧化应激与心血管疾病关系的研究进展[J].中国老年学杂志,2014,34(1)：270-273.
[3]刘亚军,郭义霖.高氧液治疗急性脑梗塞疗效观察及抗氧化损伤作用的研究[J].河北医学,2011,17(12)：1570-1573.
[4]Chen CJ, Cheng FC, Liao SL, et al. Effects of naloxoneon lactate, pyruvate metabolism and antioxidant enzyme activity in rat cerebral ischemia/ reperfusion[J]. Neurosci Lett,2000,287(2):113-116.
[5]Pan HC, Yang DY, Ou YC, et al. Neuroprotective effect of atorvastatin in an experimental model of nerve crush injury[J]. Neurosurgery,2010,67(2): 376-389.
[6]Kao TK, Ou YC, Lin SY, et al. Luteolin inhibits cytokine expression in endotoxin/cytokine-stimulated microglia[J]. JNutr Biochem,2011, 22(7):612-624.
[7]Wang J, Fields, J, Zhao, C, et al. Role of Nrf2 in protection against intracerebral hemorrhage injury in mice[J]. Free Radic Biol Med,2007,43(3):408-414.
[8]Wattanapitayakul SK, Bauer JA. Oxidative pathways in cardiovascular disease:roles, mechanisms, and therapeutic implications [J]. Pharmacol Ther, 2001,89(2):187-206.
[9]蒋福生.Hhcy对脑梗死氧化应激损伤机制的研究[J].牡丹江医学院学报, 2012,33(5)：8-11.
[10]吴思思,戴伟娟.温脾汤对小鼠缺血脑组织SOD和MDA的影响[J].中国现代药物应用,2014,8(1)：25-26.
[11]王佳,周文胜,洪秀琴.高尔基体应激与抗氧化系统在缺血脑损伤中的作用[J].中国老年学杂志,2014,34(1)：278-281.
[12]Yang Y, Liu Y, Chen L, et al. Therapeutic effect of Ginkgo biloba polysaccharide in rats with focal cerebral ischemia/reperfusion (I/R) injury[J]. Carbohydrate Polymers,2013,98(2):1383-1388.
[13]兰美华,吴红彦.中药植物多糖抗氧化作用研究进展[J].实用中医药杂志,2012,28(4)：326-327.
[14]汪志峰,仲崇俊,张毅,等.缺血后处理对大鼠局灶性脑缺血再灌注损伤保护作用的实验研究[J].南通大学学报(医学版),2012,32(6)：504-506.
[15]王志平,孙红斌.氧自由基与缺血性卒中[J].西南军医,2010,12(3)：534-536.
[16]林茵绿,李新兰,陈苡靖,等.补肾护脑方对急性脑梗死患者血清过氧化物歧化酶,丙二醛的影响及中医证候疗效观察[J].中国中医急症,2011,20(2)：187-189.
[17]王远,王海桃.银杏叶总黄酮对小鼠脑缺血再灌注损伤的保护作用[J].中国执业药师,2012,9(11)：25-28.
[18]夏强,钱令波.心脑缺血再灌注损伤的机制及防治策略研究进展[J].浙江大学学报(医学版),2010,39(6)：551-558.
[19]郝银菊,王红波,王洁,等.多糖对小鼠脑缺血再灌注损伤后氧化应激的影响[J].宁夏医学杂志,2012,34(11)：1069-1071.
[20]王全伟,凡文博,王智昊,吴扬.氧化应激与心血管疾病关系的研究进展[J].中国老年学杂志,2014,34(1)：270-273.
[21]何志杰,杨晓娇,贾杰.预运动调控脑血管功能及脑血流对脑缺血保护的作用机制研究进展[J].中国运动医学杂志,2013,32(10)：943-947.
[22]李国彰主编.神经生理学[M].北京：人民卫生出版社,2007,102-104,153-157.
[23]连瑜,李泽宇,张国华,等.一氧化氮及其合成酶在脑缺血中的作用[J].中国药物临床,2007,7(10)：779-780.
[24]王小引,李晓娟,李东亮,等.孕酮通过抑制iNOS的表达和NO的生成保护新生鼠缺氧缺血性脑损伤[J].中国应用生理学杂志,2012,28(3)：253-254.
[25]Mun CH, Lee WT, Park KA, et al. Regulation of endotheial nitric oxide synthase by agmatine after transient global cerebral ischemia in rat brain [J]. Anat Cell Biol,2010,43(3):230-240.
[26]Kikuchi K, Kawahara K, Tancharcon S, et al. The free radical scavenger edaravone rescues rats from cerebral infarction by attenuating the release of high-mobility group box-1 in neuronal cells [J]. J Pharmacol Exp Ther,2009, 329(3):865-874.
[27]邱召娟,朱查查,达庆国,等.化瘀通络方对局灶性脑缺血大鼠再灌注(MCAO)后脑组织氧自由基和NOS表达的影响[J].中华中医药学刊,2011,29(3)：509-511.
[28]Hua Q, Zhu X, Li P, et al. Refined Qing Kai Ling traditionalChinese medicinal preparation, reduces ischemic stroke induced infarct size and neurological deficits and increase expression of endothelial nitric oxide synthase[J]. Biol Pharm Bull,2008,31(4):633-637.
[29]Mehta SL, Manhas N, Raghubir R. Molecular targets in cerebral ischemia for developing novel therapeutics [J]. Brain Res Rev,2007,54(1):34-66.
[30]黄建花,何英,赖国旗.川芎嗪对IL-1β诱导的兔原代软骨细胞iNOS表达和NO合成的影响[J].第三军医大学学报,2012,34(16)：1642-1645.
[31]阚春燕,杨玉成.一氧化氮合酶家族及其基因多态性与缺血性脑卒中[J].中风与神经疾病杂志,2012,29(4)：373-374.
[32]Bae J, Kim IJ, Hong SH, et al. Association of endothelial nitric oxide synthase polymorphisms and haplotypes with ischemic stroke in Korean individuals with or without diabetes mellitus[J]. Mol Med Report,2010,3(3):509-513.
[33]冯丹,朱艳娜,王冬亮,等.西红柿红素对脂多糖诱导巨噬细胞炎症反应影响[J].中国公共卫生,2012,28(11)：1460-1462.
[34]杨翠萍,杨晓金,田真真,等.槐定碱对LPS致急性肺损伤模型小鼠血清IL-6, IL-10, NO, SOD和MDA含量的影响[J].中药药理与临床,2012,28(3)：31-3.
[1]Gelderblom M, Leypoldt F, Steinbach K, et al. Temporal and spatial dynamics of cerebral immune cell accumulation in stroke[J]. Stroke,2009,40(5): 1849-1857.
[2]Schilling M, Besselmann M, Leonhard C, et al. Microglial activation precedes and predominates over macrophage infiltration in transient focal cerebral ischemia:a study in green fluorescent protein transgenic bone marrow chimeric mice[J]. Exp Neurol,2003,183(1):25-33.
[3]Li M, Qu YZ, Zhao ZW, et al. Astragaloside IV protects against focal cerebral ischemia/reperfusion injury correlating to suppression of neutrophils adhesion-related molecules [J]. NeurochemInt,2012,60(5):458-465.
[4]Schuette-Nuetgen K, Strecker JK, Minnerup J, et al. MCP-1/CCR-2-double-Deficiency severely impairs the migration of hematogenous inflammatory cells following transient cerebral ischemia in mice[J]. Exp Neurol,2012,233 (2): 849-858.
[5]Acalovschi D, Wiest T, Hartmann M, et al. Multiple levels of regulation of the interleukin-6 system in stroke[J]. Stroke,2003,34(8):1864-1869.
[6]ZaleskaMM, Mercado ML, Chavez J, et al. The development of stroke therapeutics:promising mechanisms and translational challenges[J]. Neuro-pharmacology,2009,56(2):329-341.
[7]Williams AJ, Dave J R, Tortella FC. Neuroprotection with the proteasome inhibitor MLN519 in focal ischemic brain injury:Relation to nuclear factor κB (NF2κB), inflammatory gene expression, and leukocyte infiltration[J]. NeurochemInt,2006,49(2):106-112.
[8]ChangY, HsiaoQ ChenS, et al. Tetramethylpyrazine suppresses HIF-1α, TNF-α, and activated caspase-3 expression in middle cerebral artery occlusion-induced brain ischemia in rats[J]. Acta Pharmacol Sin,2007,28(3):327-333.
[9]FanL, WangK, ShiZ, et al. Tetramethylpyrazine protects spinal cord and reduces inflammation in a rat model of spinal cord ischemia-reperfusion injury [J]. J Vasc Surg,2011,54(1):192-200.
[10]Li XY, He JL, Liu HT, et al. Tetramethylpyrazine suppresses interleukin-8 expression in LPS-stimulated human umbilical vein endothelial cells by blocking ERK, p38 and nuclear factor-κB signaling pathways [J]. J Ethnopharmacol,2009,125(1):83-89.
[11]范治云,罗红,刘玉兰,等.川芎嗪的抗炎作用与组胺,5-羟色胺的关系[J].中药新药与临床药理,2004,15(2)：93-94.
[12]吴洪华,杨成,石增立,等.川芎嗪对缺氧缺血性脑损伤炎症细胞因子作用的实验研究[J].滨州医学院学报,2007,3(3)：161-163.
[13]段治松.大剂量川芎嗪治疗短暂性脑缺血发作的临床观察[J].医学理论与实践,2008,21(7)：788.
[14]马丽虹,李冬梅,李可建.川芎嗪注射液治疗缺血性脑卒中急性期临床疗效的系统评价[J].中国老年学杂志,2013,33(16)：3825-3827.
[15]蒋跃绒,陈可冀.川芎嗪的心脑血管药理作用及临床应用研究进展[J].中国中西医结合杂志,2013,33(5)：707-711.
[16]吕少平,孙锋,丁春霞.川芎嗪对脑缺血再灌注时细胞凋亡的影响[J].河北医学,2000,6(8)：673-675.
[17]张春兵,丁兴,詹臻.盐酸川芎嗪对大鼠脑缺血再灌注损伤的保护作用[J].江苏中医药,2008,40(4)：77-79.
[18]孙建华,汪志峰,仲崇俊,等.缺血后处理对大鼠局灶性脑缺血再灌注损伤保护作用的实验研究[J].南通大学学报医学版,2012,32(6)：504-507.
[19]患者脑循环动力学改变和川芎嗪对急性缺血性脑损伤的保护作用[J].中国中西医结合急救杂志,2005,12(4)：248-250.
[20]汪志峰,仲崇俊,张毅,等.缺血后处理对大鼠局灶性脑缺血再灌注损伤保护作用的实验研究[J].南通大学学报医学版,2012,32(6)：504-507.
[21]孙文阁,牛莉莉,潘运刚,等.川芎嗪对缺血性脑疾病防治作用的机制[J].赤峰学院学报(自然科学版),2011,27(8)：180-182.
[22]Liao SL, Kao TK, Chen WY, et al. Tetramethylpyrazine reduces ischemic brain injury in rats[J]. Neurosci Lett,2004,372(1-2):40-45.
[23]Chen CJ, Cheng FC, Liao SL, et al. Effects of naloxone on lactate, pyruvate metabolism and antioxidant enzyme activity in rat cerebral ischemia/ reperfusion[J]. Neurosci Lett,2000,287(2):113-116.
[24]Lee MY, Kuan YH, Chen HL, et al. Intravenous administration of melatonin reduces the intracerebral cellular inflammatory response following transient focal cerebral ischemia in rats[J]. J Pineal Res,2007,42(3):297-309.
[25]Gelderblom M, Leypoldt F, Lewerenz J, et al. The flavonoid fisetin attenuates postischemic immune cell infiltration, activation and infarct size after transient cerebral middle cerebral artery occlusion in mice[J]. J Cereb Blood Flow Metab, 2012,32(5):835-843.
[26]Wang YY, Chen CJ, Lin SY, et al. Hyperglycemia is associated with enhanced gluconeogenesis in a rat model of permanent cerebral ischemia[J]. Mol Cell Endocrinol,2013,367(1-2):50-56.
[27]Liu X, Zhang L, Cheng K et al. Identification of suitable plasma-based reference genes for miRNAome analysis of major depressive disorder [J]. J Affect Disord,2014, pⅱ:S0165-0327(13)00888-4. [Epub ahead of print]
[28]Kao TK, Ou YC, Raung SL, et al. Walther leafextracts protect against brain injury in ischemic rats[J]. Am J Chin Med,2010,38(3):495-516.
[29]Li M, Qu YZ, Zhao ZW, et al. Astragaloside Ⅳ protects against focal cerebral ischemia/reperfusion injury correlating to suppression of neutrophils adhesion-related molecules[J]. Neurochem.Int,2012,60(5):458-465.
[30]Chang Y, Hsiao G, Chen S, et al. Tetramethylpyrazine suppresses HIF-1α, TNF-a, and activated caspase-3 expression in middle cerebral artery occlusion-induced brain ischemia in rats[J]. Acta Pharmacol Sin,2007, 28(3):327-333.
[31]Fan L, Wang K, Shi Z, et al. Tetramethylpyrazine protects spinal cord and reduces inflammation in a rat model of spinal cord ischemia-reperfusion injury[J]. J Vasc Surg,2011,54(1):192-200.
[32]Kao TK, Ou YC, Kuo J S, et al. Neuroprotection by tetramethylpyrazine against ischemic brain injury in rats[J]. Neurochem Int,2006,48(3):166-176.
[33]Li XY, He JL, Liu HT, et al. Tetramethylpyrazine suppresses interleukin-8 expression in LPS-stimulated human umbilical vein endothelial cells by blocking ERK, p38 and nuclear factor-κB signaling pathways[J]. J Ethnopharmacol,2009,125(1):83-89.
[34]Huang J, Upadhyay UM, Tamargo RJ. Inflammation in stroke and focal cerebral ischemia[J]. SurgNeurol,2006,66(3):232-245.
[35]张雷,陆正齐.脑梗死的免疫学研究进展[J].中国神经免疫学和神经病学杂志,2013,20(5)：356-359.
[36]王恩,金国飞.白细胞与脑梗死心脑血管防治[J].2010,10(5)：381-383.
[37]郑向红,许颖.神经胶质细胞作用的研究进展[J].海峡药学,2013,25(3)：210-212.
[38]泰文娇,叶旋,鲍秀琦,等.小胶质细胞与脑缺血关系的研究进展[J].药学学报,2012,47(3)：346-353.
[39]高艳.小胶质细胞生理特点及在脑缺血损伤中的作用[J].中国组织化学与细胞化学杂志,2012,21(6)：598-602.
[40]Wen YD, Zhang HL, Qin ZH. Inflammatory mechanism in ischemic neuronal injury[J]. Neurosci Bull,2006,22(3):171-182.
[41]Kato H, Takahashi A, Itoyama Y. Cell cycle protein expression in proliferating microglia and astrocytes following transient global cerebral ischemia in the rat [J]. Brain Res Bull,2003,60(3):215-221.
[42]Ekdahl CT, Kokaia Z, Lindvall O. Brain inflammation and adult neuro-genesis: The dual role of microglia[J]. Neuroscience,2009,158(3):1021-1029.
[43]牛非,胡金凤,苑玉和,等.星形胶质细胞在脑缺血中的变化和作用[J].中国药理学通报,2011,27(10)：1342-1345.
[44]Yu AC, Lau L T. Expression of interleukin-1 alpha, tumor necrosis factor alpha and interleukin-6 genes in ast rocytes under ischemic injury[J]. Neurochem Int, 2000,36(4-5):369-377.
[45]Gabriel C, J usticia C, Camins A, et al. Activation of nuclear factor-KB in the rat brain after transient focal ischemia[J]. Brain Res Mol Brain Res,1999, 65(1):61-69
[46]Dominguez C, Delgado P, Vilches A, et al. Oxidative stress after thrombolysis-induced reperfusion in human stroke[J]. Stroke,2010,41(4):653-660.
[47]Liu B, Gao HM, Wang JY, et al. Role of nitric oxide in inflammation-mediated neurodegeneration[J]. Ann NY Acad Sci,2002, (962):318-331.
[48]Kimura Y, Matsushita N, Okuda H. Effects of baicalein isolated from Scutel-laria baicalensis on interleukin β- and tumor necrosis factor a-induced adhesion molecule expression in cultured human umbilical vein endothelial cells [J]. J Ethnopharmacol,1997,57(1):63-67.
[49]Minghetti L, Levi G. Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide[J]. Prog Neurobiol,1998,54(1):99-125.
[50]Stover JF, S akowitz OW, Schoning B, et al. Norepinephrine in fusion increases interleukin-6 in plasma and cerebrospinal fluid of brain-injured rats[J]. Med Sci Monit,2003,9(10):382-388.
[51]Morganti-kossmann MC, Rancan M, Stahel PF, et al. Inflammatory response in acute traumatic brain injury:a double-edged sword[J]. Curr Opin Crit Care, 2002,8(2):101-105.
[52]Sairanen T, Carpen O, Karjalainen-Lindsberg ML, et al. Evolution of cerebral tumor necrosis factor production during human ischemic stroke[J]. Stroke, 2001,32(8):1750-1758.
[53]孔渝涵,秦新月.不同缺血后处理对缺血再灌注大鼠脑内IL-1β,IL-6 表达的影响[J].中国老年学杂志,2012,32(14)：2984-2986.
[54]胡艳雪,范永新.血清CRP、IL-6、TNF-α、TK、EAI在老年脑梗死患者诊断的价值分析[J].现代预防医学,2012,39(9)：2375-2376,2379.
[55]Sairanen T, Carpen O, Karjalainen L, et al. Evolution of cerebral tumor necrosis factor production during human ischemic stroke[J]. Stroke,2001,32(8):1750-1758.
[56]Intiso D, Zarrelli MM, Lagioia G, et al. Tumor necrosis factor alpha serum levels and inflammatory response in acute ischemic stroke patients[J]. Neurol Sci,2004,24(6):390-396.
[1]Tanaka S, Masuda Y, Honma C, et al. Manganese promotes phorbol ester-induced interleukin-2 production via AP-1 activation in Jurkat T-cells[J]. Toxicol Lett,2012,211(3):312-318.
[2]Yang JH, Shin BY, Han JY, et al. Isorhamnetin protects against oxidative stress by activating Nrf2 and inducing the expression of its target genes [J]. Toxicol Appl Pharmacol,2014,74(2):293-301.
[3]Chen YR, Tan TH. The c-Jun N-terminal kinase pathway and apoptotic signaling (review)[J]. Int J Oncol,2000,16(4):651-62.
[4]Ki YW, Park JH, Lee JE, et al. JNK and p38 MAPK regulate oxidative stress and the inflammatory response in chlorpyrifos-induced apoptosis[J]. Toxicol Lett,2013,218(3):235-45.
[5]Li Y, He D, Zhang X, et al. Protective effect of celastrol in a rat cerebral ischemia model:down-regulating p-JNK, p-c-Jun and NF-κB[J]. Brain Res, 2012,1464:8-13.
[6]LiuY, Wang H, ZhuY, et al. The protective effect of nordihydroguaiaretic acid on cerebral ischemia/reperfusion injury is mediated by the JNK pathway [J]. Brain Res.2012,1445:73-81.
[7]Murata Y, Fujiwara N, Seo JH. Delayed inhibition of c-Jun N-terminal kinase worsens outcomes after focal cerebral ischemia[J]. J Neurosci,2012,32(24): 8112-8115.
[8]Wang LW, Tu YF, Huang CC, et al. JNK signaling is the shared pathway linking neuroinflammation, blood-brain barrier disruption and oligodendroglial apoptosis in the white matter injury of the immature brain[J]. J Neuroinfla-mmation,2012,9:175.
[9]李国彰.神经生理学[M].人民卫生出版社,2007：114-116.
[10]Nijboer CH, van der Kooij MA, van Bel F, et al. Inhibition of the JNK/AP-1 pathway reduces neuronal death and improves behavioral outcome after neonatal hypoxic-ischemic brain injury[J]. Brain Behavior Immun,2010, 24(5):812-821.
[11]Shih AY, Johnson DA, Wong G, et al.Coordinateregulation of lutathione biosynthesis and release by Nrf2-expressing glia potently protects neurons romoxidative stress[J]. J Neurosci,2003,23(8):3394-3406
[12]Gong P, Stewart D, Hu, B, et al. Activation of the mouse heme oxygenase-1 gene by 15-deoxy-Delta (12,14)-prostaglandin J(2) is mediated by the stress response elements and transcription factor Nrf2[J]. Antioxid Redox Signal. 2002,4(2):249-257.
[13]Kraft AD, Lee JM, Johnson DA, et al. Neuronal sensitivityto kainic acid is dependent on the Nrf2-mediated actions of the antioxidant response element [J]. Journal of Neurochemistry,2006,98:1852-1865.
[14]童海达,王佳茗,宋英Keapl-Nrf2-ARE在机体氧化应激损伤中的防御作用[J].癌变.畸变.突变,2013,25(1)：71-75.
[15]甘露,袁萱,张红,等Nrf2/Keap1抗氧化系统与缺血性脑病[J].农垦医学,2011,33(1):79-82.
[16]Li W, Jain MR, Chen C, et al. Nrf2 Possesses a redox-insensitive nuclear export signal overlapping with the leucine zipper motif[J]. J Biol Chem, 2005,280(31):28430-28438.
[17]Kobayashi A, Ohta T, Yamamoto M. Unique function of theNrf2-Keap 1 pathway in the inducible expression of antioxidant and detoxifying enzymes [J]. Methods Enzymol,2004,(378):273-286.
[18]Kraft AD, Lee JM, Johnson DA, et al. Neuronal sensitivityto kainic acid is dependent on theNrf2-mediated actions of the antioxidant response element [J]. Journal of Neurochemistry,2006,98(6):1852-1865.
[19]Zhang DD. Mechanistic studies of the Nrf2-Keap1 signaling pathway[J]. Drug Metab Rev,2006,38(4):769-789.
[20]朱凤臣,蒋电明.Nrf2/ARE转导通路在中枢神经系统疾病中作用的研究进展[J].中国生物制品学杂志,2011,24(6)：741-744.
[21]Jeong WS, Keum YS, Chen C, et al. Differential expression and stability of endogenous nuclear factor E2-related factor Nrf2 by natural chemopreven-tive compounds in HepG2 human hepatoma cells[J]. J Biochem Mol Biol, 2005,38(2):167-176.
[22]钟敏.Nrf2-Keap1抗氧化系统研究进展[J].中国公共卫生,2006,22(3)：360-362.
[2]陈灏珠主编.实用内科学[M].第11版.北京：人民卫生出版社,2001
[3]李华德,颜国平.地塞米松联合甘露醇应用于急性重症脑血管病脑保护作用的临床研究[J].中国医学创新,2014,11(2)：31-33.
[4]封菲,丁美萍.创伤性脑水肿的发生机制及研究进展[J].心脑血管病防治,2013,13(6)：472-474.
[5]李军,曾邦雄.脑缺血损伤级联反应的研究进展[J].国外医学(麻醉学与复苏分册),2001,22(6)：364-368.
[6]甘照濡,桑栋楠.脑缺血再灌注损伤级联反应研究进展[J].医学综述,2009,15(1)：43-45.
[7]李传云,李伟华.脑缺血再灌注损伤机制的现代研究进展[J].中华现代中西医杂志,2005,3：1744-1746
[8]于炳新,吕传真.脑缺血半暗带研究进展[J].中国临床神经科学,2002,(10)：96-99.
[9]Racay P, Tatarkova Z, ChomovaM,et al. Mitochondrial calciumtransport and mitochondrial dysfunction after global brain ischemiain rat hippocampus[J].Neurochem Res,2009,34(8):1469-1478.。
[10]Zhang W, Petrovic JM, Callaghan D, et al. Evidence that hypoxia-in-ducible factor-1 (HIF-1) mediates transcriptional activation of interleukin-lbeta(IL-1 beta) in astrocyte cultures[J]. J Neuroimmuno,2006,174(12):63-73.
[11]Ichas F, Mazat JP. From Calcium signaling to cell death:two conformations for the mitochondrial permeability transition pore. Switching from low to high conductance state [J]. Biochim Biophys Acta,1998,1366(1-2):33-50.
[12]Brookes S, Yoon Y, Robotham JL, et al. Calcium ATP and ROS:a mitochondrial love-hate triangle [J]. Am J Physiol Cell Physio,2004,287(4): C817-C833.
[13]杨惠玲,潘景轩,吴伟康.高级病理生理学[M].第2版.北京：科学出版社,2006：27-31.
[14]Harukuni I, Bhardwaj A. Mechanisms of brain injuryafter global cerebral ischemia[J]. Neurol Clin,2006,24(1):1-21.
[15]淘录岭,刘轲.中药单体对脑缺血再灌注损伤保护的实验研究进展[J].时珍国医国药,2012,23(12)：3107-3109.
[16]李国彰主编.神经生理学[M].北京：人民卫生出版社,2007,149-151.
[17]Sen CK, Packer L. Antioxidant and redox regulation of gene transcription[J]. FASEB J,1996,10(7):709-720.
[18]Zhong LT, Sarafian T, kane DJ, et al. Bcl-2 inhibits deathof central neural cells induced by multiple agents[J]. Prcc Natl Acad Sci U S A,1993,90 (10):4533-4537.
[19]Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death[J]. Cell, 1993,(74):609-619.
[20]洪浩,刘国卿.缺血性脑血管疾病治疗的抗氧化应激策略[J].中国药理学通报,2004,(20)：19-24.
[21]陈念航.脑内一氧化氮与脑缺血损伤[J].国外医学生理、病理科学与临床分册,1995,15(4)：244-247.
[22]刘巍,王钜.一氧化氮,一氧化氮合成酶及其抑制剂在缺血性脑损伤研究中的进展[J].实验动物科学与管理,2006,23(3)：43-46.
[23]Mun CH, Lee WT, Park KA, et al. Regulation of endotheial nitric oxide synthase by agmatine after transient globalcerebral ischemia in rat brain [J].Anat Cell Biol,2010,43 (3):230-240.
[24]连瑜,李泽宇,张国华.一氧化氮及其合成酶在脑缺血中的作用[J].中国药物临床,2007,7(10)：779-780.
[25]齐聪儒,孔祥玉.中药对脑缺血再灌注损伤保护作用的研究进展[J].承德医学院学报,2008,25(4)：416-418.
[26]Zaleska MM, Mercado ML, Chavez J, et al. The development of stroket herapeutics:promising mechanisms and translational challenges [J]. Neuro-pharmacology,2009,56 (2):329-341.
[27]Khan M, Elango C, Ansari MA, et al. Caffeic acid phenethylester reduces neurovascular inflammation and protects rat brain following transient focal cerebral ischemia[J]. Neurochem,2007,102 (2):365-377.
[28]张昆南,曹金娟,刘世民,等.大鼠脑梗死后脑组织TNF-α、GFAP、NSE、 BDNF、Nestin的表达和神经功能变化[J].中国神经免疫学和神经病学杂志,2013(5)：305-310
[29]Wang Q, Tang XN, Midori A. The inflammatory responseins troke[J]. Neuro-immunol,2007,184 (1-2):53-68.
[30]Williams AJ, Dave J R, Tortella FC. Neuroprotection with the proteasome inhibitor MLN 519 in focal ischemic brain injury:Relation to nuclear factorkcB (NF2κB), inflammatory gene expression, and leukocyte infiltration[J] Neurochem Int,2006,49 (2):106-112.
[31]Minghetti L, Levi G. Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide.Prog[J]. Neurobiol.1998.54(1):99-125.
[32]Huang J, Upadhyay UM, Tamargo RJ. Inflammation in stroke and focal cerebral ischemia[J]. Surg Neurol,2006,66 (3):232-245.
[33]Pantoni L, Sarti C, Inzitari D. Cytokines and cell adhesion molecules in cerebral ischemia experimental bases and therapeutic perspective [J]. Arterioscler Thromb Vasc Biol,1998,18 (4):503-513.
[34]Wen YD, Zhang HL, Qin ZH. Inflammatory mechanism in ischemic neuronal injury[J]. Neurosci Bull,2006,22 (3):171-182.
[35]Ekdahl CT, Kokaia Z, Lindvall O. Brain inflammation and adult neurogenesis: The dual role of microglia [J]. Neuroscience,2009,158 (3):1021-1029.
[36]Yu AC, Lau L T. Expression of interleukin-1 alpha, tumor necrosis factor alpha and interleukin-6 genes in ast rocytes under ischemic injury[J]. Neurochem Int, 2000,36 (4-5):369-377.
[37]Gabriel C, J usticia C, Camins A, et al. Activation of nuclear factor-κB in the rat brain after transient focal ischemia[J]. Brain Res Mol Brain Res,1999,65 (1):61-69.
[38]Wen YD, Zhang HL, Qin ZH. Inflammatory mechanism in ischemic neuronal injury[J]. Neurosci Bull,2006,22 (3):171-182.
[39]Kato H, Takahashi A, Itoyama Y. Cell cycle protein expression in proliferating microglia and astrocytes following transient global cerebral ischemia in the rat [J]. Brain Res Bull,2003,60 (3):215-221.
[40]Arumugam TV, Woodruff TM, Lat hia JD, et al. Neuroprotection in stroke by complement inhibition and immunoglobulin therapy [J]. Neuroscience,2009, 158 (3):1074-1089.
[41]Ekdahl CT, Kokaia Z, Lindvall O. Brain inflammation and adult neurogenesis: The dual role of microglia [J]. Neuroscience,2009,158 (3):1021-1029.
[42]Liu B, Gao HM, Wang JY, et al. Role of nitric oxide ininflammation-mediated neurodegeneration[J]. Ann NYAcad Sci,2002,962:318-331.
[43]Kimura Y, Matsushita N, Okuda H. Effects of baicalein isolated from Scutellaria baicalensis on interleukin β- and tumor necrosis factor a-induced adhesion molecule expression in cultured human umbilical vein endothelial cells [J]. J Ethnopharmacol,1997,57(1):63-67.
[44]睢燕,周名雄.脑缺血再灌注损伤中炎症反应的免疫学机制[J].解剖与临床,2007,12(6)：436-438.
[45]Yamasaki Y, Matsuura N, Shozuhara H, et al. Interleukin-1 as pathogenetic mediator of ischemic brain damage in rats[J]. Stroke,1995; 26:676-680.
[46]Davies CA, Loddick SA, Toulmond S. The progression and topographic distribution of interleukin-1 beta expression after permanent middle cerebral artery occlusion in the rat[J]. J Cereb Blood Flow Metab,1999,19(1):87-98.
[47]Stover JF, Sakowitz OW, Schoning B, et al. Norepinephrine infusion increases interleukin-6 in plasma and cerebrospinal fluid of braininjured rats[J]. Med Sci Monit,2003,9(10):382-388.
[48]Morganti-Kossmann MC, Rancan M, Stahel PF, et al. Inflammatory response in acute traumatic brain injury:a double-edged sword[J]. Curr Opin Crit Care,2002, 8(2):101-105.
[49]Kovanen PT, KaartinenM, Paavonen T. Infiltrates of activated mast cells at the site of coronary atheromatous erosion or rupture in myocardial infarction[J]. Circulation,1995,92(5):1084-1088
[50]Clark WM, Rinker L G, LessovNS, et al. Lack of interleukin-6 expression is not protective against focal central nervous system ischemia[J]. Stroke,2000,31 (7):1715-1720.
[51]向赟,董大翠,刘庆莹.脑缺血与白细胞介素-6的变化[J].江汉大学学报(自然科学版),2005,23(2)：83-87.
[52]张国良血塞通对急性脑梗死患者血清TNF-α、IL-1β和IL-6浓度影响的临床研究[J].心脑血管病防治,2011,11(5)：378-380.
[53]Huang J, Upadhyay UM, Tamargo RJ. Inflammation in stroke and focal cerebral ischemia[J]. Surg Neurol,2006,66 (3):232-245.
[54]肖岚,黎杏群.白介素-6与脑缺血损伤[J].国外医学(神经病学神经外科学分册),2000,27(5)：258-261.
[55]Campbell IL, Erta M, Lim SL, et al. Trans-signaling is a dominant mechanism for the pathogenic actions of interleukin-6 in the brain[J]. J Neurosci,2014,34 (7):2503-2513.
[56]杨爱华,薛会光,初开秋,等.血清C反应蛋白与白介素-6检测及其与脑梗死相关关系探讨[J].现代预防医学,2008,35(21)：4291-4292.
[57]金美兰,杨桂芝.血浆白介素-8与急性脑梗死的相关性探讨中国医学创新[J].2012,(14)：56-57
[58]叶飞,罗建勤,陈建,等.血清NSE、IL-6和IL-8水平与急性脑梗死的关系[J].浙江实用医学,2012,(3)：192-193.
[59]Malisan F, Briere F, Bridon JM, et al. Interleukin-10 induces immunoglobulin G isotype switch recombination in human CD40-activated naive B lymphocytes[J]. J Exp Med,1996, (183):937-947..
[60]周婷,丁美萍,闻树群.急性脑梗死患者血清脂联素与IL-10的关系及意义[J].心脑血管病防治,2010,10(1)：17-19.
[61]Sairanen T, Carpen O, Karjalainen-Lindsberg ML, et al. Evolution of cerebral tumor necrosis factor-alpha production during human ischemic stroke[J]. Stroke, 2001,32 (8):1750-1758.
[62]Intiso D, Zarrelli MM, Lagioia G, et al. Tumor necrosis factor alpha serum levels and inflammatory response in acute ischemic st rokepatients[J]. Neurol Sci,2004, 24 (6):390-396.
[63]张明义,韩俊英,张蕴,等.血清肿瘤坏死因子-α对急性缺血性脑卒中患者预后的影响[J].中国现代神经疾病杂志,2007,7(3)：234-237.
[64]李沙,黄艳秋,游红琴,等.脑缺血再灌注损伤模型大鼠炎性反应相关信号研究[J].中国神经免疫学和神经病学杂志,2012,(6)：453-461.
[65]张莉莉,王景周,周华东,等.肿瘤坏死因子-α在大鼠脑缺血再灌注损伤中的作用机制[J].中华老年医学杂志,2003,22(2)：37-39
[66]Guo RB, Wang GF, Zhao AP, et al.Paeoniflorin protects against ischemia-induced brain damages in rats via inhibiting MAPKs/NF-κB-mediated inflammatory responses[J].PLoS One,2012,7(11):e49701.
[67]Zhang XM, Zheng XY, Sharkawi SS,et al. Possible protecting role of TNF-α in kainic acid-induced neurotoxicity via down-regulation of NFκB signaling pathway[J].Curr Alzheimer Res,2013,10(6):660-669.
[68]Guo RB, Wang GF, Zhao AP, et al. Paeoniflorin protects against ischemia-induced brain damages in rats via inhibiting MAPKs/NF-κB-mediated inflammatory responses[J]. PLoS One,2012,7(11):e49701.
[69]王晓平,罗永杰,马思文,等.Bcl-2,半胱氨酸-天冬氨酸蛋白酶在SD大鼠脑梗死急性期的动态表达研究实用医院临床杂志[J].2013,10(5)：53-56,57.
[70]施勤,刘继明.细胞的线粒体调控与Bcl-2基因家族[J].上海免疫学杂志,2000,20(1)：59-61.
[71]Niizuma K, Yoshioks H, Chen H, et al. Mitochondrial and apoptotic neuronal death signaling pathways in cerebral ischemia[J]. Biochim Biophy Acta,2010, 1802(1):92-99.
[72]Qiao H, Dong L, Protective effect of luteolin in experimental ischemic stroke: upregulated SOD1, CAT, Bcl-2 and claudin-5, down-regulated MDA and Bax expression[J]. Neurochem Res,2012,37(9):2014-2024.
[73]牟芳芳,于永娟.银杏叶提取物EGb761对大鼠脑缺血再灌注后细胞凋亡及Bcl-2,Bax蛋白表达的影响[J].上海中医药大学学报,2012,26(3)：78-81.
[74]支文煜.脑缺血再灌注损伤引起的线粒体功能障碍及丹参酮IIA的保护作用研究[J].实用心脑肺血管病杂,2010,18(10)：1389-1391.
[75]张予阳,史琳琳,郝冬海,等.Bcl-2在缺血性神经细胞损伤中的作用及药物的影响[J].中国药理学通报,2010,26(1)：21-24.
[76]徐开屏,孙风艳.线粒体释放的促凋亡蛋白和细胞凋亡[J].中国神经科学杂志,2002,18(4)：732-735.
[77]Haddad JJ. The role of Bax/Bcl-2 and procaspase peptides in hypoxia/ reperfusion-dependent regulation of MAPK (ERK):Discordant proteomic effect of MAPK (p38) [J]. Protein Pept Lett,2007,14(4):361-371.
[78]Gill MB, Bockhorst K, Narayana P, et al. Bax shuttling after neonatal hypoxia schemia:hyperoxia effects[J]. J Neurosci Res,2008,86(16):3584-3604.
[79]Schemdt-kastner R, Teuettner J, Zhao W, et al. Differential changes of bax, caspase-3, and p21 mRNA expression after transient focal brain ischemia in the rats[J]. Brain Res Mol Brain Res,2000,79(1-2):88-101.
[80]Zhao H, Yenari MA, Cheng D, et al. Bcl-2 over expression protects against neuron loss within the ischemia margin following experimental stroke and inhibits cytochrome C translocation and caspase-3 activity [J]. Neurochem, 2003,85(4):1026-1036
[81]Cheng CY, Su SY, Tang NY, et al. Ferulic acid inhibits nitric oxide-induced apoptosis by enhancing gaba (b1) receptor expression intransient focal cerebral ischemia in rats[J]. Acta Pharmacol Sin,2010,31(8):889-899.
[82]Broughton BR, Reutens DC, Sobey CG Apoptotic mechanisms after cerebral ischemia[J]. Stroke,2009,40(5):e331-339.
[83]Brunelle JK, Letai A. Control of mitochondrial apoptosis by the Bcl-2 family [J]. J Cell Sci,2009,122(4):437-444.
[84]Mehta S L, Manhas N, Raghubir R. Molecular targets in cerebral ischemia for developing novel therapeutics[J]. Brain Res Rev,2007,54(1):34-66.
[85]Karatas H, Aktas Y, Ozdemir Y, et al. A nanomedicine transports a peptide caspase-3 inhibitor across the blood-brain barrier and provides neuroprotection [J]. J Neurosci,2009,29(44):13761-13769
[86]刘广义.脑缺血后Caspase-3蛋白Bcl-2和Bax基因表达在神经损伤中的作用[J].中国康复,2010,25(3)：163-166.
[87]陈月桥,王丽,武建华.细胞凋亡信号传导途径研究进展[J].中国实用医药,2007,2(33)：186-187.
[88]王爱莲,李懿萍.线粒体和凋亡[J].国外医学(临床生物化学与检验分册),2000,21(6):287-288
[89]Blomgran R, Zheng L, Stendahl O. Cathepsin-cleaved Bid promotes apoptosis in human neutrophils via oxidative stress-induced lysosomal membrane permeabilization [J]. J Leukoc Biol,2007,81(5):1213-1223.
[90]Ho PK, Hawkins CJ.Mammalian initiator apoptotic caspases[J].FEBS J,2005, 272 (21):5436-5453.
[91]Gu Qing, Wang Ji-de, Harry HX, et al. Activation of the caspase-8/Bid and Bax pathways in aspirin-induced apoptosisin gastric cancer [J].Carcino-genesis, 2005,26(3):541-546.
[92]庞涛,陈婉蓉.线粒体与细胞凋亡的研究进展[J].卫生毒理学杂志,2003,6(17)：122-124.
[93]Liu B, Gao HM, Wang JY, et al. Role of nitric oxide ininflammation-mediated neurodegeneration[J]. Ann NY Acad Sci,2002, (962):318-331.
[94]Boehning D, Patterson RL, Sedaghat L, et al. Cytochrome c binds alto inositol (1,4,5)trisphosphate receptors, amplifying calcium-dependent apoptosis[J]. Nat Cell Biol,2003,5(12):1051-1061.
[95]Boehning D, van Roswm DB, Patterson RL, et al. A peptide inhibitor of cytochrome c/ inositol 1,4,5 trisphosphate receptor binding blocks intrinsic and extrinsic cell death pathways[J]. Proc Natl Acad Sci USA,2005,102 (5):1466-1471.
[96]Chaudhry P, Srinivasan R, Patel FD, et al. Serum soluble Fas levels and prediction of response to platinum-based chemotherapy in epithelial ovaria cancer [J]. Int J Cancer,2008,122(8):1716-1721.
[97]Villa-Morales M, Santos J, Prez-Gmez E, et al. A role for the Fas/FasL system in modulating genetic susceptibility to T-cell lymphoblastic lymphomas[J]. Cancer Res,2007,67(11):5107-5116.
[98]Tephly LA,CarterAB. Differential expression and oxidation of MKP-1 modulates TNF alpha gene expression[J]. Am J Respir Cell Mol Biol,2007,37(3):366-374.
[99]Higuchi Y, Chan TO, Brown MA, et al. Cardioprotection afforded by NF-kappa B ablation is associated with activation of Akt in mice overexpressing TNF-alpha [J]. Am J Heart Circ Physiol,2006,290(2):H590-H598.
[100]蒋杞英,王志新,大鼠局灶性脑缺血再灌注脑组织神经细胞凋亡与Bcl-2, Bcl-x1蛋白检测[J].郑州大学学报(医学版),2004,3(9)：428-431.
[101]赵航,王敏.缺血再灌注大鼠脑皮质Bcl-2、Bax和Caspase-3的动态表达[J].中国老年医学杂志,2012,7(13)：2801-280.
[1]黄启福,王谦主编.病理学[M].第3版.北京：科学出版社,2013,11-20.
[2]李桂源主编.病理生理学[M].第2版.北京：人民卫生出版社,2013,248-261.
[3]金惠铭主编.病理生理学[M].第8版.北京：人民卫生出版社,2013,129-136.
[4]鞠躬主编.神经生物学[M].北京：人民卫生出版社,2004,159-181.
[5]黄文林,朱孝峰主编.信号转导[M].北京：人民卫生出版社,2005,1-11.
[6]刘景生主编.细胞信息与调控[M].第2版.北京：中国协和医科大学出版社,2004,185-255
[7]卢建等主编.受体信号转导系统与疾病[M].济南：山东科学技术出版社,2002,34-420.
[8]金伯泉主编.细胞和分子免疫学[M].北京：科学出版社,2003,1-39
[9]Brea D, Sobrino T, Ramos-Cabrer P, et al. Inflammator and neuroimmuno-modulatory changes in acute cerebral ischemia[J]. Cerebrovasc Dis,2009, 27(Suppll):48-64.
[10]吴克复.细胞通讯与疾病.北京：科学出版社,2006,216-223,242-264.
[11]Rosenzweig HL, Minami M, Lessov NS, et al. Endotoxin preconditioning protects against the cytotoxic effects of TNF-alpha after stroke:a novel role for TNF-alpha in LPS-ischemic tolerance[J]. Cereb Blood Flow Metab,2007,27 (10):1663-1674.
[12]Akira S, Uematsu S, Takcuchi O. Pathogen recognition and innate immunity [J]. Cell,2006,124(4):783-801.
[13]李丽燕.Toll样受体的研究进展[J].临床医学工程,2011,18(3)：467-469.
[14]王德成,余敏,余锐萍,等.Toll样受体研究进展[J].动物医学进展,2008,29(2)：56-60.
[15]Uematsu S, Akira S. Toll-like receptors and type I interferons [J]. Journal of biological chemistry,2007,282(5):15319-15324.
[16]Kaisho T, Akira S. Toll-like receptor function and signaling[J]. Allergy Clinimmunol,2006,117(5):979-987.
[17]Hyakkoku K, Hamanaka J, Tsuruma K, et al. Toll-like receptor 4(TLR4), but not TLR3 or TLR9, knockout mice have neuroprotective effects against focal cerebral ischemia[J]. Neuroscience,2010,171(1):258-267.
[18]Tang SC, Arumugam TV, Xu X, et al. Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits[J]. Proc Natl Acad Sci USA,2007, 104(34):13798-13803.
[19]Ziegler G, Harhausen D, Schepers C, et al. TLR2 has a detrimental role in mouse transient focal cerebral ischemia[J]. Biochem Biophys Res Commun,2007, 359(3):574-579.
[20]孙鹏,张清,韩继媛,等.体外模拟脑缺血再灌注条件下BV-2细胞TLR4信号途径对TLR2表达的影响中国科学(C辑),2009,(11)：1013-1018.
[21]Wang YC, Lin S, Yang QW. Toll-like receptors in cerebral ischemic inflammatory injury[J]. Journal of Neuroinflammation,2011,8(1):134-144.
[22]Cao CX, Yang QW, LV FL, et al. Reduced cerebral ischemia-reperfusion injury in Toll-like receptor 4 deficient mice[J]. Biochem Biophys Res Commun,2007, 353(2):509-514.
[23]张清,孙鹏,冯新民,等.Toll样受体4在大鼠脑缺血再灌注损伤中的表达及其意义[J].华中科技大学学报(医学版),2008,37(2)：219-221.
[24]李国彰.神经生理学[M].人民卫生出版社,2007：115-116.
[25]姜勇.LPS介导细胞激活的信号转导：从CD14到p38MAPK通路的研究[J].生理科学进展,1999,30(1)：29-34.
[26]Hu BR, Liu CL, Park DJ. Alteration of MAP kinase pathways after transient forebrain ischemia [J]. J Cereb Blood Flow Metab,2000,20(7):1089-1095.
[27]Raingeaud J, Gupta S, Rogers JS, et al. Pro-inflammatory cytokines and environmental stress cause p38 mitogen activated protein kinase activation by dual phosphory lation on tyrosine and threonine [J]. J Biol Chem,1995,270(13): 7420-7426.
[28]Lee JC, Laydon JT, Mc Donnell PC, et al. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis [J]. Nature,1994,372 (6508):739-746.
[29]Nijboer CH, van der Kooij, MA, van Bel F, et al.Inhibition of the JNK/AP-1 pathway reduces neuronal death and improves behavioral outcome after neonatal hypoxic-ischemic brain injury[J]. Brain Behavior Immun,2010,24(5):812-821.
[30]Tanaka S, Masuda Y, Honma C, et al. Manganese promotes phorbol esterinduced interleukin-2 production via AP-1 activation in Jurkat T-cells[J]. Toxicol Lett, 2012,211(3):312-318.
[31]Chen YR, Tan TH. The c-Jun N-terminal kinase pathway and apoptotic signaling (review) [J]. Int J Oncol,2000,16(4):651-62.
[32]黎增辉,廖爱军.JNK信号通路[J].国际病理科学与临床杂志,2010,30(3)：273-276.
[33]Sabapathy K. Role of the JNK pathway in human diseases [J]. Prog Mol Biol Transl Sci,2012, (106):145-169.
[34]MoriY, GotohY. Role of the JNK signaling pathway[J]. Tanpakushitsu Kakusan Koso,2008,53(10):1252-1257.
[35]李欣,魏红艳,胡春林,等.SAPK/JNK信号通路在脑梗死后神经元凋亡中的作用[J].中国病理生理杂志,2011,(8)：1552-1556.
[36]Kaminska B, Gozdz A, Zawadzka M, et al. MAPK signal transduction underlying brain inflammation and gliosis as therapeutic target. Anat Rec (Hoboken) [J].2009,292(12):1902-1913.
[37]Jawien J, Gajda M, Mateuszuk L, et al. Inhibition of Nuclear factor-JB attenuates atherosclerosis in apoE/LDLR-Double knockout mice [J]. Physiol Pharmacol, 2005,56(3):483-489.
[38]Brasier AR. The NF-kappaB regulatory network [J]. Cardiovasc Toxicol,2006, 6(2):111-130.
[39]Brevetti G, Schiano V, Chiariello M. et al. Cellular adhesion molecules and peripheral arterial disease [J]. Vase Med,2006, 11(1):39-47.
[40]Nijboer CH, Heijnen CJ, Groenendaal F, et al. A dual role of the NF-kappa B pathway in neonatal hypoxic-ischem ic brain damage[J]. Stroke,2008,39(9): 2578-2586.
[41]甘露,袁萱,张红,等.Nrf2/Keap1抗氧化系统与缺血性脑病[J].农垦医学,2011,33(1)：79-82.
[42]朱凤臣,蒋电明.Nrf2/ARE转导通路在中枢神经系统疾病中作用的研究进展[J].中国生物制品学杂志,2011,24(6)：741-744.
[43]Shih AY, Johnson DA, Wong G, et al. Coordinateregulation of glutathione biosynthesis and release by Nrf2-expressing gliapotently protects neurons from oxidative stress[J]. J Neurosci,2003,23(8):3394-3406.
[44]Li W, Jain MR, Chen C, et al. Nrf2 Possesses a redoxin sensitive nuclear export signal overlapping with the leucine zipper motif[J]. BioChem,2005,280(31): 28430-28438.
[45]童海达,王佳茗,宋英. Keapl-Nrf2-ARE在机体氧化应激损伤中的防御作用[J].癌变,畸变,突变,2013,25(1)：71-75.
[46]Kobayashi A, Ohta T, Yamamoto M. Unique function of the Nrf2-Keapl pathway in the inducible expression of antioxidant and detoxifying enzymes [J]. Methods Enzymol,2004, (378):273-286.
[47]Kraft AD, Lee JM, Johnson DA, et al. Neuronal sensitivityto kainic acid is dependent on the Nrf2-mediated actions of the antioxidant response element[J]. Journal of Neurochemistry,2006,98(6):1852-1865.
[48]Jeong WS, Keum YS, Chen C, et al. Differential expression and stability of endogenous nuclear factor E2-related factor 2 (Nrf2) by natural chemo-preventive compounds in HepG2 human hepatoma cells[J]. J Biochem Mol Biol, 2005,38(2):167-176.
[49]钟敏Nrf2-Keap1抗氧化系统研究进展[J].中国公共卫生,2006,22(3)：360-362.
[50]Kraft AD, Johnson DA, Johnson JA. Nuclear factor E2-related factor 2-dependent antioxidant response element activation by tertbutylhydroquinone and sulforaphane occurring preferentially in astrocytes conditions neurons against oxidative insult[J]. J Neurosci,2004,24(5):1101-1112.
[1]张琦,叶夷露,颜吟雪,等.黄连解毒汤对小鼠脑缺血慢性神经损伤的保护作用[J].浙江大学学报(医学版),2009,38(1)：75-80.
[2]刘斌,蔡梅芝,李爱华,等.参芎化瘀胶囊对大鼠急性脑缺血再灌注损伤的保护作用[J].中国实验方剂学杂志,2012,18(11)：229-232.
[3]刘敬霞,李建生,俞维.星萎承气汤和补阳还五汤对脑缺血大鼠海马神经元损伤的影响[J].中国实验方剂学杂志,2012,18(12)：233-237.
[4]唐红梅,白雪.中医药治疗缺血性脑卒中的优势探讨[J].中医药导报,2011,17(10)：90-92.
[5]王清任.医林改错[M].北京：人民军医出版社,2007.
[6]杨佳昕.王清任补阳还五汤治疗中风病文献研究[J].实用中医内科杂志,2012,26(11)：10-13.
[7]刘泰,黄德庆.补阳还五汤治疗急性缺血性中风随机对照试验的meta分析[J].辽宁中医杂志,2012,39(10)：1913-1915.
[8]徐谦,陈新林,沈耿.等.补阳还五汤干预中风先兆证的Meta分析[J].中国实验方剂学杂志,2013,19(16)：339-343.
[9]欧迎跃.补阳还五汤联合西医治疗急性脑梗死临床疗效观察[J].内蒙古中医药,2013,(3)：56-57.
[10]邵承玲.补阳还五汤加减治疗脑梗死恢复期的临床疗效分析[J].中国医药指南,2013,11(23)：273-274.
[11]刘永平.补阳还五汤在缺血性中风恢复期肢体麻木患者的应用[J].中国中医药现代远程教育,2013,11(9)：15-16.
[12]董征亮、陈永斌、姜薇.补阳还五汤及其加减方治疗脑梗死的临床研究进展[J].中国当代医药,2013,20(9)：24-27.
[13]周赛男,蔺晓源,易健,等.补阳还五汤对脑缺血大鼠神经功能及细胞形态的影响[J].中国实验方剂学杂志,2013,19(2)：251-254.
[14]杨春根.补阳还五汤对大鼠脑缺血再灌注损伤的保护作用[J].现代中药研究 与实践,2010,24(1)：36-39.
[15]柯锋,吴洪,邓春龄,等.补阳还五汤对气虚血瘀型和非气虚血瘀型缺血性中风病人的疗效比较[J].中西医结合心脑血管杂志,2005,(11)：962-964.
[16]杨虹,魏桂荣,李红戈.脑梗死血清MMP-3与MMP-9的动态变化及临床意义[J].中国康复,2005,20(5)：278-280.
[17]蓝艳.补阳还五汤对气虚血瘀型缺血性脑卒中患者血浆基质金属蛋白酶影响[J].福建中医药,2013,44(1)：21-22.
[18]许慧娜,陈光明.补阳还五汤对缺血性脑损害神经细胞凋亡影响的研究进展[J].现代中西医结合杂志,2011,20(12)：1551-1553.
[19]刘俊娥,张继平.补阳还五汤抗脑缺血神经细胞凋亡实验研究进展[J].中国中医药信息杂志,2011,18(9)：110-112.
[20]王新高,童萼塘,孙圣刚.补阳还五汤对脑缺血再灌注大鼠皮质神经细胞凋亡的影响[J].现代中西医结合杂志,2005,14(3)：306-309.
[21]曲宏达,佟丽,沈剑刚,等.补阳还五汤药物血清对体外培养大鼠皮层神经元缺氧后P53和P21表达的影响[J].中国中酉医结合杂志,2004,24(2)：133-135.
[22]廖春来,伶丽,陈育尧.补阳还五汤对大鼠脑缺血半暗区Caspase-3 mRNA表达的影响[J].中国临床康复,2004,8(19)：3821-3823.
[23]尹天雷,蔡光先,李勇敏,等.补阳还五汤对脑缺血模型大鼠脑组织NGF及PI3K/AKT信号转导途径的影响[J].中国中医药科技,2008,15(1)：24-25.
[24]Sun HJ, Li TM, Wang GX. Protective effect of Xuefuzhuyu Decoction for focal cerebral ischemia[J]. China Journal of Chinese Medicine,2013,28(7):981-983.
[25]雷燕,王军辉,李忠文.血府逐瘀汤组方配伍及加减运用的实验研究概述[J].中国实验方剂学杂志,2001,7(6)：57-59.
[26]李应宏.血府逐瘀汤治疗急性缺血性脑卒中的疗效[J].中国康复理沦与实践,2013,19(3)：263-265.
[27]孙寒静,黎同明,王桂香.血府逐瘀汤对大鼠局灶性脑缺血模型的保护作用[J].中医学报,2013,28(7)：981-983.
[28]王倬,王宁,王东披.血府逐瘀汤对缺血缺氧性脑损伤大鼠的保护作用[J]. 浙江中医杂志,2009,44(11)：793-795.
[29]Raner MS, Priestley JV, Ncmahon SB. Functional regeneration of sensory axons into the adult spinal cord [J]. Nature,2000,403(6767):312-316.
[30]Sofroniew MV, Howe CL, Mobley WC. Nerve growth factor signaling, neuroprotection, and neural repair[J]. Annu Rev Neurosci,2001,(24):1217-1281.
[31]Chiaretti A, Antonelli A, Mastrangelo A, et al. lnterleukin-6 and nerve growth factor upregulation correlates with improved outcome in children with severe traumatic brain injury [J]. J neurotrauma,2008,25(3):225-234.
[32]吕中,王宁,王东披.益气活血法对缺氧缺血性脑损伤保护作用的实验研究[J].中华中医药学刊,2011,29(7)：1552-1555.
[33]陶勇军,陈云志.《医林改错》方药临床运用[J].实用中医内科杂志,2011,25(6)：33-34.
[34]凌敬.通窍活血汤加减治疗急性脑梗死的疗效观察[J].世界中医药,2013,8(3)：303-305.
[35]吴苏宁.内皮素与缺血性脑血管疾病的治疗研究进展[J].国外医学老年医学分册,1999,20(3)：97-99.
[36]孙琳,李义召.降钙素基因相关肽与脑血管病[J].山东医药,2001,41(1)：58-60.
[37]汪宁,刘青云,彭代银,等.活血通窍汤对脑缺血大鼠脑组织中CGRP, ET, IL-1β,TNF-α的影响[J].中成药,2005,27(11)：1295-1297.
[38]汪宁,刘青云,彭代银,等.活血通窍汤对脑缺血大鼠的保护作用及机制研究[J].中国中医药信息杂志,2004,11(5)：407-409.
[39]崔英慧.活血通窍汤治疗短暂性脑缺血发作的疗效及对体内炎症反应的影响[J].现代中西医结合杂志,2012,21(23)：2572-2573.
[40]汪宁,许风清,邓奕,陈威,等.通窍活血汤对谷氨酸损伤PC 12细胞保护作用的实验研究[J].中国中医药科技,2008,15(2)：101-102.
[41]KaoTK, Liang SM. Pharmacological research and development of Tetramethyl-pyrazine in the role of cardiovascular and cerebrovascular[J]. SJT Tcm,2011, 5(2):58-68.
[42]王丽,吕圭源,陈素红.川芎嗪药理作用的研究进展[J].医学信息(上旬刊),2011,24(3)：1116-1118.
[43]马丽虹,李冬梅,李可建.川芎嗪注射液治疗缺血性脑卒中急性期临床疗效的系统评价[J].中国老年学杂志,2013,33(16)：3825-3827.
[44]孙建华.脑梗死患者脑循环动力学改变和川芎嗪对急性缺血性脑损伤的保护作用[J].中国中西医结合急救杂志,2005,12(4)：248-249.
[45]楚冰,邵国富,周旭平.川芎嗪对大鼠局灶性脑缺血后额叶、丘脑、小脑病理形态改变的影响[J].神经疾病与精神卫生,2004,(4)：250-251.
[46]甘照濡,桑栋楠.脑缺血再灌注损伤级联反应研究进展[J].医学综述,2009,15(1)：43-45.
[47]李建生,李建国,赵君玫等.川芎嗪和参麦注射液对老龄大鼠脑缺血再灌注多器官损伤的作用[J].国际中西医结合养生学与康复医学学术研讨会论文汇编[C].2000,251-257.
[48]邵国富,包仕尧.川芎嗪、丹参、丹皮酚和当归对脑缺血后再灌注期脑血流量的影响[J].中国中西医结合杂志,1998,(S1)：57-59,361.
[49]张景秋,赵喜庆,吉训明,等.川芎嗪对大鼠脑缺血再灌注损伤的作用[J].临床误诊误治,2012,24(2)：41-43.
[50]刘德山,朱爱华,陈克忠.川芎嗪注射液对脑缺血再灌注家兔体感诱发电位的影响[J].山东大学学报(医学版),2003,41(4)：405-407.
[51]张萌,邸东华,李盈.川芎嗪对大鼠脑缺血再灌注后线粒体功能的影响[J].辽宁中医药大学学报,2009,(2)：172-173.
[52]Acalovschi D, Wiest T, Hartmann M, et al. Multiple levels of regulation of the interleukin-6 system in stroke[J]. Stroke,2003,34(8):1864-1869.
[53]Khan M, Elango C, Ansari MA, et al. Caffeic acid phenethylesterreduces neurovascular inflammation and protects rat brain following transient focal cerebral ischemia[J]. J Neurochem,2007,102(2):365-377.
[54]Williams AJ, Dave J R, Tortella FC. Neuroprotection with the proteasome inhibitor MLN 519 in focal ischemic brain injury:Relation to nuclear factor κB (NF2κB), inflammatory gene expression, and leukocyte infiltration[J]. Neurochem Int,2006,49(2):106-112.
[55]Wang Q, Tang XN, Yenari MA. The inflammatory response instroke [J]. Neuroimmunol,2007,184(1-2):53-68.
[56]高长越,周华东,邓娟,等.川芎嗪对脑缺血再灌注损伤后细胞粘附作用的影响[J].中国临床康复,2006,(35)：178-179,192.
[57]李建民,陈长香,赵雅宁,等.川芎嗪对沙鼠前脑缺血-再灌注损伤后学习记忆的影响[J].河北医药,2010,32(1)：19-21.
[58]陆将,曹义战,仲月霞,等.川芎嗪对局灶性脑缺血后MPO活性及白细胞介素-6含量的影响[J].中国中医急症,2008,17(4)：508-509.
[59]陈龙,王文华,朱胜强,等.川芎嗪对大鼠脑缺血再灌注后1L-1β和ICAM-1表达的影响[J].临床医药实践,2009,18(8)：561-562.
[60]孙寒静,郑缅华,梁天山.川芎嗪注射液对急性脑梗死患者血清sCD40L及hsCRP水平的影响[J].上海中医药大学学报,2013,27(4)：39-41.
[61]Dominique TV, Renaud T, Xavier W, et al. Isoflurane inhaled at the onset of reperfusion potentiates the cardoprotective effect of ischemic postconditioning through a NO-dependent mechanisn [J]. J Cardliovasc Pharmacol,2006,47(3): 487-492.
[62]丁兴.盐酸川芎嗪抗大鼠脑缺血再灌注损伤的实验研究[J].甘肃中医,2008,21(9)：58-59.
[63]阮琴.川芎挥发油川芎嗪对小鼠脑缺血再灌注损伤的保护作用[J].浙江中医杂志.2009,44(9)：642-643.
[64]徐芝秀.川芎嗪对大鼠脑缺血再灌注损伤的保护作用[J].实用中医药杂志,2007,23(7)：411-413.
[65]张春兵,丁兴,詹臻.盐酸川芎嗪对大鼠脑缺血再灌注损伤的保护作用[J].江苏中医药,2008,40(4)：77-79.
[66]祁存芳,张建水,田玉梅,等.川芎嗪对成年大鼠脑缺血再灌注损伤后nNOS的表达和神经的影响[J].南方医科大学学报,2007,27(6)：771-774.
[67]Kinderlerer A R, Pombo Gregoire I, Hamdulay S S, et al. Heme oxygenase-1 expression enhances vascular endothelial resistance to complement-mediated injury through induction of decay-accelerating factor:a role for increased bilirubin and ferritin[J]. Blood,2009,113(7):1598-1607.
[68]冯海松,黎红华.川芎嗪注射液对急性脑梗死患者的抗氧化保护作用[J].河南中医,2013,33(9)：1466-1467.
[69]Brittain T, Skommer J, Raychaudhuri S, et al. An antiapoptotic neuroprotective role for neurologic[J]. Int J Mol Sci,2010,11 (6):2306-2321.
[70]MartinLJ, Price AC, Mcclendon KB, et al. Early events of target deprivation axotomy-induced neuronal apoptosis in vivo:oxidative stress, DNA damage, p53 phosphorylation and subcellular redistribution of death proteins[J]. J Neurochem,2003,85(1):234-247.
[71]Doyle KP, Simon RP, Stenzel-Poore MP. Mechanisms of ischemic brain damage [J].Neuropharmacology,2008,55(3):310-318.
[72]Tabira T. Singificance of intracellular a beta in Alzheimer's disease[J]. Nihon Shinkei Seishin Yakurigaku Zasshi,2002,22(5):175-180.
[73]Nakatsuka H, Ohta S, Tanaka J, et al. Cytochrome C release from mitochondria to the cytosol was suppressed in the ischemia-tolerance-induced hippocampal CA1 region after 5-min forebrain ischemia in gerbils[J]. Neurosci Lett,2000, 278(1-2):53-56.
[74]吕少平,孙锋,王春霞.川芎嗪对脑缺血再灌注时细胞凋亡的影响[J].河北医学,2000,6(8)：673-675.
[75]王世龙,林原,唐泽耀.川芎嗪在各类神经系统损伤中的保护作用及其机制研究进展[J].中国药理学通报,2010,26(4)：438-442.
[76]张辉,牛书雷,王发亮,等.脑缺血再灌注大鼠额叶皮质内Bcl-2和HSP70的表达及川芎嗪,尼莫地平的干预作用[J].神经解剖学杂志,2009,25(1)：79-83.
[77]李庚华,杨迎春,任占川.川芎嗪对大鼠脑缺血再灌注损伤后大脑皮质Bcl-2表达的影响[J].解剖学杂志,2010,33(1)：82-85.
[78]柳朝阳,孙鹏,苗志,张涛,等.川芎嗪抑制大鼠局灶性脑缺血损伤神经元凋亡的作用[J].中国老年学杂志,2010,30(11)：1519-1521.
[79]张辉,牛书雷,王发亮,等.脑缺血再灌注大鼠额叶皮质内Bcl-2和HSP70的表达及川芎嗪,尼莫地平的干预作用[J].神经解剖学杂志,2009,25(1)： 79-83.
[80]Li M, Zhao MQ, Kumar Durairajan SS, et al. Protective effect of tetramethylpyrazine and salvianolic acid B on apoptosis of rat cerebral microvascular endothelial cell under high shear stress[J]. Clin Hemorheol Microcirc,2008,38(3):177-187.
[81]张晓丽,蒋丽娜,赵荧,等.川芎嗪对脑缺血再灌注后皮质Bax mRNA表达的影响[J].时珍国医国药,2008,19(9)：2109-2110.
[82]赵秋振,刘玉利,张辉,等.川芎嗪对大鼠脑缺血再灌注海马神经元BaxmRNA表达的影响[J].时珍国医国药,2011,22(2)：435-436.
[83]肖成云,刘军涛.川芎嗪对大鼠脑缺血再灌注Bcl-2、c-fos、Caspase-3的影响[J].河南中医学院学报,2007,22(4)：28-29.
[84]曲友直,高国栋,赵振伟,等.川芎嗪,黄芪对脑缺血再灌注后神经细胞凋亡及Fos蛋白表达的影响[J].卒中与神经疾病,2004,11(2)：111-112.
[85]吕少平,孙锋,王春霞.川芎嗪对脑缺血再灌注时细胞凋亡的影响[J].河北医学,,2000,6(8)：673-675.
[86]Xiao R, Qiao JT, Zhao HF, et al. Sodium selenite induces apoptosis in cultured cortical neurons with special concomitant changes in expression of the apoptosis-related genes[J]. Neurotoxicology,2006,27(4):478-484.
[87]季旭明,车萍,齐东梅,等.川芎嗪干预大鼠局灶性脑缺血模型神经元细胞凋亡的作用机制研究[J].中华中医药学刊,2012,30(11)：2461-2464.
[88]Kao TK, Ou YC, Kuo JS, et al. Neuroprotection by tetramethylpyrazine against ischemic brain injury in rats[J]. Neurochem Int,2006,48(3):166-176.
[1]李传云,李伟华.脑缺血再灌注损伤机制的现代研究进展[J].中华现代中西医杂志,2005,3(19)：1744-1746.
[2]戴甲培,冯斌.治疗急性缺血性脑中风神经保护药物研发的进展和展望[J].2012,31(2)：50-55.
[3]唐红梅,白雪.中医药治疗缺血性脑卒中的优势探讨[J].中医药导报,2011,17(10)：90-92
[4]欧迎跃.补阳还五汤联合西医治疗急性脑梗死临床疗效观察[J].内蒙古中医药,2013,(3)：56-57.
[5]邵承玲.补阳还五汤加减治疗脑梗死恢复期的临床疗效分析[J].中国医药指南,2013,11(23)：273-274.
[6]董征亮,陈永斌,姜薇.补阳还五汤及其加减方治疗脑梗死的临床研究进展[J].中国当代医药,2013,20(9)：24-27.
[7]周赛男,蔺晓源,易健,等.补阳还五汤对脑缺血大鼠神经功能及细胞形态的影响[J].中国实验方剂学杂志,2013,19(2)：251-254.
[8]杨春根.补阳还五汤对大鼠脑缺血再灌注损伤的保护作用[J].现代中药研究与实践,2010,24(1)：36-39.
[9]马丽虹,李冬梅,李可建.川芎嗪注射液治疗缺血性脑卒中急性期临床疗效的系统评价[J].中国老年学杂志,2013,33(16)：3825-3827.
[10]张景秋,赵喜庆,吉训明,等.川芎嗪对大鼠脑缺血再灌注损伤的作用[J].临床误诊误治,2012,24(2)：41-43.
[11]阮琴.川芎挥发油川芎嗪对小鼠脑缺血再灌注损伤的保护作用[J].浙江中医杂志,2009,44(9)：642-643.
[12]丁兴.盐酸川芎嗪抗大鼠脑缺血再灌注损伤的实验研究[J].甘肃中医,2008,21(9)：58-59.
[13]张春兵,丁兴,詹臻.盐酸川芎嗪对大鼠脑缺血再灌注损伤的保护作用[J].江苏中医药,2008,40(4)：77-79.
[14]徐芝秀.川芎嗪对大鼠脑缺血再灌注损伤的保护作用[J].实用中医药杂志,2007,23(7)：411-413.
[15]Kao TK, Ou YC, Kuo JS, et al. Neuroprotection by tetramethylpyrazine against ischemic brain injury in rats[J]. NeurochemInt,2006,48(3):166-176.
[16]Liao SL, Kao TK, Chen WY, et al. Tetramethylpyrazine reduces ischemic brain injury in rats[J]. Neurosci Lett,2004,372(1-2):40-45.
[17]Chen CJ, Cheng FC, Liao SL, et al. Effects of naloxone on lactate, pyruvate metabolism and antioxidant enzyme activity in rat cerebral ischemia/reper-fusion[J]. Neurosci Lett,2000,287(2):113-116.
[18]Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats [J]. Stroke,1989,20(1):84-89.
[19]屈会化,赵琰,卢建秋,等.缺血性中风动物模型研究现状[J].中国实验动物学报,2010,18(4)：94-97.
[20]Longa EZ, Weinstein PR, Carlson S, et al. Reversible middlecerebral artery occlusion without craniectomy in rats[J]. Stroke,1989,20(1):84-91.
[21]Chang CY, Kuan YH, Li JR, et al. Docosahexaenoic acid reduces cellular inflammatory response following permanent focal cerebral ischemia in rats[J]. J Nutr Biochem,2013,24 (12):2127-2137. (IF 4.552)
[22]Kao TK, Chang CY, Ou YC, et al. Tetramethylpyrazine reduces cellular inflammatory response following permanent focal cerebral ischemia in rats[J]. Exp Neurol,2013, (247):188-201. (IF 4.645)
[23]Wang YY, Chen CJ, Lin SY, et al. Hyperglycemia is associated with enhanced gluconeogenesis in a rat model of permanent cerebral ischemia[J]. Mol Cell Endocrinol,2013,367(1-2):50-56. (IF 4.039)
[24]Wang YY, Lin SY, Chuang YH, et al. Activation of hepatic inflammatory pathways via sympathetic system is associated with hepatic insulin resistance in male ischemic stroke rats[J]. Endocrinology (In Press) 2014, (IF4.717)
[25]Li F, Fisher M. Animal modeling for developing stroke therapy. In:Fisher M (Ed.) Stroke therapy[M]. Woburn, MA:Butterworth-Heinemann,2001, 83-96.
[26]Joshi CN, Jain SK, Murthy PS. An optimized triphenyltetrazolium chloride method for identification of cerebral infarcts[J]. Brain Res Brain Res Protoc 2004,13(1):11-17.
[27]Panickar KS, Qin B, Anderson RA. Ischemia-induced endothelial cell swelling and mitochondrial dysfunction are attenuated by cinnamtannin D1, green tea extract, and resveratrol in vitro[J]. Nutr Neurosci,2014, Epub ahead of print.
[28]Neumann-Haefelin T, Kastrup A, de Crespigny A, et al. Serial MRI after transient focal cerebral ischemia in rats:dynamics of tissue injury, blood-brain barrier damage, and edema formation[J]. Stroke,2000,31(8):1965-1972.
[29]Yang Y, Rosenberg GA. Blood-brain barrier breakdown in acute and chronic cerebrovascular disease[J]. Stroke,2011,42(11):3323-3328.
[30]Ueno M, Molecular anatomy of the brain endothelial barrier:an overview of the distributional feature[J]. Curr Med Chem.2007,14(11):1199-1206.
[31]李玉芳,刘坤,倪月秋,等.川芎嗪对大鼠脑缺血再灌注后血脑屏障的保护作用及Claudin-5表达的影响[J].中国医科大学学报,2013,4(6)：511-514.
[32]刘洋,刘敬霞,李娟,等.中医药调控脑缺血损伤血脑屏障通透性作用机制的研究进展[J].辽宁中医杂志,2013,40(10)：2160-2163.
[1]王文静,孙呈皓,戴敏超,等.氧化应激对脑缺血再灌注损伤后自噬调控机制[J].中国微侵袭神经外科杂志,2013,18(6)：275-279.
[2]王全伟,凡文博,王智昊,等.氧化应激与心血管疾病关系的研究进展[J].中国老年学杂志,2014,34(1)：270-273.
[3]刘亚军,郭义霖.高氧液治疗急性脑梗塞疗效观察及抗氧化损伤作用的研究[J].河北医学,2011,17(12)：1570-1573.
[4]Chen CJ, Cheng FC, Liao SL, et al. Effects of naloxoneon lactate, pyruvate metabolism and antioxidant enzyme activity in rat cerebral ischemia/ reperfusion[J]. Neurosci Lett,2000,287(2):113-116.
[5]Pan HC, Yang DY, Ou YC, et al. Neuroprotective effect of atorvastatin in an experimental model of nerve crush injury[J]. Neurosurgery,2010,67(2): 376-389.
[6]Kao TK, Ou YC, Lin SY, et al. Luteolin inhibits cytokine expression in endotoxin/cytokine-stimulated microglia[J]. JNutr Biochem,2011, 22(7):612-624.
[7]Wang J, Fields, J, Zhao, C, et al. Role of Nrf2 in protection against intracerebral hemorrhage injury in mice[J]. Free Radic Biol Med,2007,43(3):408-414.
[8]Wattanapitayakul SK, Bauer JA. Oxidative pathways in cardiovascular disease:roles, mechanisms, and therapeutic implications [J]. Pharmacol Ther, 2001,89(2):187-206.
[9]蒋福生.Hhcy对脑梗死氧化应激损伤机制的研究[J].牡丹江医学院学报, 2012,33(5)：8-11.
[10]吴思思,戴伟娟.温脾汤对小鼠缺血脑组织SOD和MDA的影响[J].中国现代药物应用,2014,8(1)：25-26.
[11]王佳,周文胜,洪秀琴.高尔基体应激与抗氧化系统在缺血脑损伤中的作用[J].中国老年学杂志,2014,34(1)：278-281.
[12]Yang Y, Liu Y, Chen L, et al. Therapeutic effect of Ginkgo biloba polysaccharide in rats with focal cerebral ischemia/reperfusion (I/R) injury[J]. Carbohydrate Polymers,2013,98(2):1383-1388.
[13]兰美华,吴红彦.中药植物多糖抗氧化作用研究进展[J].实用中医药杂志,2012,28(4)：326-327.
[14]汪志峰,仲崇俊,张毅,等.缺血后处理对大鼠局灶性脑缺血再灌注损伤保护作用的实验研究[J].南通大学学报(医学版),2012,32(6)：504-506.
[15]王志平,孙红斌.氧自由基与缺血性卒中[J].西南军医,2010,12(3)：534-536.
[16]林茵绿,李新兰,陈苡靖,等.补肾护脑方对急性脑梗死患者血清过氧化物歧化酶,丙二醛的影响及中医证候疗效观察[J].中国中医急症,2011,20(2)：187-189.
[17]王远,王海桃.银杏叶总黄酮对小鼠脑缺血再灌注损伤的保护作用[J].中国执业药师,2012,9(11)：25-28.
[18]夏强,钱令波.心脑缺血再灌注损伤的机制及防治策略研究进展[J].浙江大学学报(医学版),2010,39(6)：551-558.
[19]郝银菊,王红波,王洁,等.多糖对小鼠脑缺血再灌注损伤后氧化应激的影响[J].宁夏医学杂志,2012,34(11)：1069-1071.
[20]王全伟,凡文博,王智昊,吴扬.氧化应激与心血管疾病关系的研究进展[J].中国老年学杂志,2014,34(1)：270-273.
[21]何志杰,杨晓娇,贾杰.预运动调控脑血管功能及脑血流对脑缺血保护的作用机制研究进展[J].中国运动医学杂志,2013,32(10)：943-947.
[22]李国彰主编.神经生理学[M].北京：人民卫生出版社,2007,102-104,153-157.
[23]连瑜,李泽宇,张国华,等.一氧化氮及其合成酶在脑缺血中的作用[J].中国药物临床,2007,7(10)：779-780.
[24]王小引,李晓娟,李东亮,等.孕酮通过抑制iNOS的表达和NO的生成保护新生鼠缺氧缺血性脑损伤[J].中国应用生理学杂志,2012,28(3)：253-254.
[25]Mun CH, Lee WT, Park KA, et al. Regulation of endotheial nitric oxide synthase by agmatine after transient global cerebral ischemia in rat brain [J]. Anat Cell Biol,2010,43(3):230-240.
[26]Kikuchi K, Kawahara K, Tancharcon S, et al. The free radical scavenger edaravone rescues rats from cerebral infarction by attenuating the release of high-mobility group box-1 in neuronal cells [J]. J Pharmacol Exp Ther,2009, 329(3):865-874.
[27]邱召娟,朱查查,达庆国,等.化瘀通络方对局灶性脑缺血大鼠再灌注(MCAO)后脑组织氧自由基和NOS表达的影响[J].中华中医药学刊,2011,29(3)：509-511.
[28]Hua Q, Zhu X, Li P, et al. Refined Qing Kai Ling traditionalChinese medicinal preparation, reduces ischemic stroke induced infarct size and neurological deficits and increase expression of endothelial nitric oxide synthase[J]. Biol Pharm Bull,2008,31(4):633-637.
[29]Mehta SL, Manhas N, Raghubir R. Molecular targets in cerebral ischemia for developing novel therapeutics [J]. Brain Res Rev,2007,54(1):34-66.
[30]黄建花,何英,赖国旗.川芎嗪对IL-1β诱导的兔原代软骨细胞iNOS表达和NO合成的影响[J].第三军医大学学报,2012,34(16)：1642-1645.
[31]阚春燕,杨玉成.一氧化氮合酶家族及其基因多态性与缺血性脑卒中[J].中风与神经疾病杂志,2012,29(4)：373-374.
[32]Bae J, Kim IJ, Hong SH, et al. Association of endothelial nitric oxide synthase polymorphisms and haplotypes with ischemic stroke in Korean individuals with or without diabetes mellitus[J]. Mol Med Report,2010,3(3):509-513.
[33]冯丹,朱艳娜,王冬亮,等.西红柿红素对脂多糖诱导巨噬细胞炎症反应影响[J].中国公共卫生,2012,28(11)：1460-1462.
[34]杨翠萍,杨晓金,田真真,等.槐定碱对LPS致急性肺损伤模型小鼠血清IL-6, IL-10, NO, SOD和MDA含量的影响[J].中药药理与临床,2012,28(3)：31-3.
[1]Gelderblom M, Leypoldt F, Steinbach K, et al. Temporal and spatial dynamics of cerebral immune cell accumulation in stroke[J]. Stroke,2009,40(5): 1849-1857.
[2]Schilling M, Besselmann M, Leonhard C, et al. Microglial activation precedes and predominates over macrophage infiltration in transient focal cerebral ischemia:a study in green fluorescent protein transgenic bone marrow chimeric mice[J]. Exp Neurol,2003,183(1):25-33.
[3]Li M, Qu YZ, Zhao ZW, et al. Astragaloside IV protects against focal cerebral ischemia/reperfusion injury correlating to suppression of neutrophils adhesion-related molecules [J]. NeurochemInt,2012,60(5):458-465.
[4]Schuette-Nuetgen K, Strecker JK, Minnerup J, et al. MCP-1/CCR-2-double-Deficiency severely impairs the migration of hematogenous inflammatory cells following transient cerebral ischemia in mice[J]. Exp Neurol,2012,233 (2): 849-858.
[5]Acalovschi D, Wiest T, Hartmann M, et al. Multiple levels of regulation of the interleukin-6 system in stroke[J]. Stroke,2003,34(8):1864-1869.
[6]ZaleskaMM, Mercado ML, Chavez J, et al. The development of stroke therapeutics:promising mechanisms and translational challenges[J]. Neuro-pharmacology,2009,56(2):329-341.
[7]Williams AJ, Dave J R, Tortella FC. Neuroprotection with the proteasome inhibitor MLN519 in focal ischemic brain injury:Relation to nuclear factor κB (NF2κB), inflammatory gene expression, and leukocyte infiltration[J]. NeurochemInt,2006,49(2):106-112.
[8]ChangY, HsiaoQ ChenS, et al. Tetramethylpyrazine suppresses HIF-1α, TNF-α, and activated caspase-3 expression in middle cerebral artery occlusion-induced brain ischemia in rats[J]. Acta Pharmacol Sin,2007,28(3):327-333.
[9]FanL, WangK, ShiZ, et al. Tetramethylpyrazine protects spinal cord and reduces inflammation in a rat model of spinal cord ischemia-reperfusion injury [J]. J Vasc Surg,2011,54(1):192-200.
[10]Li XY, He JL, Liu HT, et al. Tetramethylpyrazine suppresses interleukin-8 expression in LPS-stimulated human umbilical vein endothelial cells by blocking ERK, p38 and nuclear factor-κB signaling pathways [J]. J Ethnopharmacol,2009,125(1):83-89.
[11]范治云,罗红,刘玉兰,等.川芎嗪的抗炎作用与组胺,5-羟色胺的关系[J].中药新药与临床药理,2004,15(2)：93-94.
[12]吴洪华,杨成,石增立,等.川芎嗪对缺氧缺血性脑损伤炎症细胞因子作用的实验研究[J].滨州医学院学报,2007,3(3)：161-163.
[13]段治松.大剂量川芎嗪治疗短暂性脑缺血发作的临床观察[J].医学理论与实践,2008,21(7)：788.
[14]马丽虹,李冬梅,李可建.川芎嗪注射液治疗缺血性脑卒中急性期临床疗效的系统评价[J].中国老年学杂志,2013,33(16)：3825-3827.
[15]蒋跃绒,陈可冀.川芎嗪的心脑血管药理作用及临床应用研究进展[J].中国中西医结合杂志,2013,33(5)：707-711.
[16]吕少平,孙锋,丁春霞.川芎嗪对脑缺血再灌注时细胞凋亡的影响[J].河北医学,2000,6(8)：673-675.
[17]张春兵,丁兴,詹臻.盐酸川芎嗪对大鼠脑缺血再灌注损伤的保护作用[J].江苏中医药,2008,40(4)：77-79.
[18]孙建华,汪志峰,仲崇俊,等.缺血后处理对大鼠局灶性脑缺血再灌注损伤保护作用的实验研究[J].南通大学学报医学版,2012,32(6)：504-507.
[19]患者脑循环动力学改变和川芎嗪对急性缺血性脑损伤的保护作用[J].中国中西医结合急救杂志,2005,12(4)：248-250.
[20]汪志峰,仲崇俊,张毅,等.缺血后处理对大鼠局灶性脑缺血再灌注损伤保护作用的实验研究[J].南通大学学报医学版,2012,32(6)：504-507.
[21]孙文阁,牛莉莉,潘运刚,等.川芎嗪对缺血性脑疾病防治作用的机制[J].赤峰学院学报(自然科学版),2011,27(8)：180-182.
[22]Liao SL, Kao TK, Chen WY, et al. Tetramethylpyrazine reduces ischemic brain injury in rats[J]. Neurosci Lett,2004,372(1-2):40-45.
[23]Chen CJ, Cheng FC, Liao SL, et al. Effects of naloxone on lactate, pyruvate metabolism and antioxidant enzyme activity in rat cerebral ischemia/ reperfusion[J]. Neurosci Lett,2000,287(2):113-116.
[24]Lee MY, Kuan YH, Chen HL, et al. Intravenous administration of melatonin reduces the intracerebral cellular inflammatory response following transient focal cerebral ischemia in rats[J]. J Pineal Res,2007,42(3):297-309.
[25]Gelderblom M, Leypoldt F, Lewerenz J, et al. The flavonoid fisetin attenuates postischemic immune cell infiltration, activation and infarct size after transient cerebral middle cerebral artery occlusion in mice[J]. J Cereb Blood Flow Metab, 2012,32(5):835-843.
[26]Wang YY, Chen CJ, Lin SY, et al. Hyperglycemia is associated with enhanced gluconeogenesis in a rat model of permanent cerebral ischemia[J]. Mol Cell Endocrinol,2013,367(1-2):50-56.
[27]Liu X, Zhang L, Cheng K et al. Identification of suitable plasma-based reference genes for miRNAome analysis of major depressive disorder [J]. J Affect Disord,2014, pⅱ:S0165-0327(13)00888-4. [Epub ahead of print]
[28]Kao TK, Ou YC, Raung SL, et al. Walther leafextracts protect against brain injury in ischemic rats[J]. Am J Chin Med,2010,38(3):495-516.
[29]Li M, Qu YZ, Zhao ZW, et al. Astragaloside Ⅳ protects against focal cerebral ischemia/reperfusion injury correlating to suppression of neutrophils adhesion-related molecules[J]. Neurochem.Int,2012,60(5):458-465.
[30]Chang Y, Hsiao G, Chen S, et al. Tetramethylpyrazine suppresses HIF-1α, TNF-a, and activated caspase-3 expression in middle cerebral artery occlusion-induced brain ischemia in rats[J]. Acta Pharmacol Sin,2007, 28(3):327-333.
[31]Fan L, Wang K, Shi Z, et al. Tetramethylpyrazine protects spinal cord and reduces inflammation in a rat model of spinal cord ischemia-reperfusion injury[J]. J Vasc Surg,2011,54(1):192-200.
[32]Kao TK, Ou YC, Kuo J S, et al. Neuroprotection by tetramethylpyrazine against ischemic brain injury in rats[J]. Neurochem Int,2006,48(3):166-176.
[33]Li XY, He JL, Liu HT, et al. Tetramethylpyrazine suppresses interleukin-8 expression in LPS-stimulated human umbilical vein endothelial cells by blocking ERK, p38 and nuclear factor-κB signaling pathways[J]. J Ethnopharmacol,2009,125(1):83-89.
[34]Huang J, Upadhyay UM, Tamargo RJ. Inflammation in stroke and focal cerebral ischemia[J]. SurgNeurol,2006,66(3):232-245.
[35]张雷,陆正齐.脑梗死的免疫学研究进展[J].中国神经免疫学和神经病学杂志,2013,20(5)：356-359.
[36]王恩,金国飞.白细胞与脑梗死心脑血管防治[J].2010,10(5)：381-383.
[37]郑向红,许颖.神经胶质细胞作用的研究进展[J].海峡药学,2013,25(3)：210-212.
[38]泰文娇,叶旋,鲍秀琦,等.小胶质细胞与脑缺血关系的研究进展[J].药学学报,2012,47(3)：346-353.
[39]高艳.小胶质细胞生理特点及在脑缺血损伤中的作用[J].中国组织化学与细胞化学杂志,2012,21(6)：598-602.
[40]Wen YD, Zhang HL, Qin ZH. Inflammatory mechanism in ischemic neuronal injury[J]. Neurosci Bull,2006,22(3):171-182.
[41]Kato H, Takahashi A, Itoyama Y. Cell cycle protein expression in proliferating microglia and astrocytes following transient global cerebral ischemia in the rat [J]. Brain Res Bull,2003,60(3):215-221.
[42]Ekdahl CT, Kokaia Z, Lindvall O. Brain inflammation and adult neuro-genesis: The dual role of microglia[J]. Neuroscience,2009,158(3):1021-1029.
[43]牛非,胡金凤,苑玉和,等.星形胶质细胞在脑缺血中的变化和作用[J].中国药理学通报,2011,27(10)：1342-1345.
[44]Yu AC, Lau L T. Expression of interleukin-1 alpha, tumor necrosis factor alpha and interleukin-6 genes in ast rocytes under ischemic injury[J]. Neurochem Int, 2000,36(4-5):369-377.
[45]Gabriel C, J usticia C, Camins A, et al. Activation of nuclear factor-KB in the rat brain after transient focal ischemia[J]. Brain Res Mol Brain Res,1999, 65(1):61-69
[46]Dominguez C, Delgado P, Vilches A, et al. Oxidative stress after thrombolysis-induced reperfusion in human stroke[J]. Stroke,2010,41(4):653-660.
[47]Liu B, Gao HM, Wang JY, et al. Role of nitric oxide in inflammation-mediated neurodegeneration[J]. Ann NY Acad Sci,2002, (962):318-331.
[48]Kimura Y, Matsushita N, Okuda H. Effects of baicalein isolated from Scutel-laria baicalensis on interleukin β- and tumor necrosis factor a-induced adhesion molecule expression in cultured human umbilical vein endothelial cells [J]. J Ethnopharmacol,1997,57(1):63-67.
[49]Minghetti L, Levi G. Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide[J]. Prog Neurobiol,1998,54(1):99-125.
[50]Stover JF, S akowitz OW, Schoning B, et al. Norepinephrine in fusion increases interleukin-6 in plasma and cerebrospinal fluid of brain-injured rats[J]. Med Sci Monit,2003,9(10):382-388.
[51]Morganti-kossmann MC, Rancan M, Stahel PF, et al. Inflammatory response in acute traumatic brain injury:a double-edged sword[J]. Curr Opin Crit Care, 2002,8(2):101-105.
[52]Sairanen T, Carpen O, Karjalainen-Lindsberg ML, et al. Evolution of cerebral tumor necrosis factor production during human ischemic stroke[J]. Stroke, 2001,32(8):1750-1758.
[53]孔渝涵,秦新月.不同缺血后处理对缺血再灌注大鼠脑内IL-1β,IL-6 表达的影响[J].中国老年学杂志,2012,32(14)：2984-2986.
[54]胡艳雪,范永新.血清CRP、IL-6、TNF-α、TK、EAI在老年脑梗死患者诊断的价值分析[J].现代预防医学,2012,39(9)：2375-2376,2379.
[55]Sairanen T, Carpen O, Karjalainen L, et al. Evolution of cerebral tumor necrosis factor production during human ischemic stroke[J]. Stroke,2001,32(8):1750-1758.
[56]Intiso D, Zarrelli MM, Lagioia G, et al. Tumor necrosis factor alpha serum levels and inflammatory response in acute ischemic stroke patients[J]. Neurol Sci,2004,24(6):390-396.
[1]Tanaka S, Masuda Y, Honma C, et al. Manganese promotes phorbol ester-induced interleukin-2 production via AP-1 activation in Jurkat T-cells[J]. Toxicol Lett,2012,211(3):312-318.
[2]Yang JH, Shin BY, Han JY, et al. Isorhamnetin protects against oxidative stress by activating Nrf2 and inducing the expression of its target genes [J]. Toxicol Appl Pharmacol,2014,74(2):293-301.
[3]Chen YR, Tan TH. The c-Jun N-terminal kinase pathway and apoptotic signaling (review)[J]. Int J Oncol,2000,16(4):651-62.
[4]Ki YW, Park JH, Lee JE, et al. JNK and p38 MAPK regulate oxidative stress and the inflammatory response in chlorpyrifos-induced apoptosis[J]. Toxicol Lett,2013,218(3):235-45.
[5]Li Y, He D, Zhang X, et al. Protective effect of celastrol in a rat cerebral ischemia model:down-regulating p-JNK, p-c-Jun and NF-κB[J]. Brain Res, 2012,1464:8-13.
[6]LiuY, Wang H, ZhuY, et al. The protective effect of nordihydroguaiaretic acid on cerebral ischemia/reperfusion injury is mediated by the JNK pathway [J]. Brain Res.2012,1445:73-81.
[7]Murata Y, Fujiwara N, Seo JH. Delayed inhibition of c-Jun N-terminal kinase worsens outcomes after focal cerebral ischemia[J]. J Neurosci,2012,32(24): 8112-8115.
[8]Wang LW, Tu YF, Huang CC, et al. JNK signaling is the shared pathway linking neuroinflammation, blood-brain barrier disruption and oligodendroglial apoptosis in the white matter injury of the immature brain[J]. J Neuroinfla-mmation,2012,9:175.
[9]李国彰.神经生理学[M].人民卫生出版社,2007：114-116.
[10]Nijboer CH, van der Kooij MA, van Bel F, et al. Inhibition of the JNK/AP-1 pathway reduces neuronal death and improves behavioral outcome after neonatal hypoxic-ischemic brain injury[J]. Brain Behavior Immun,2010, 24(5):812-821.
[11]Shih AY, Johnson DA, Wong G, et al.Coordinateregulation of lutathione biosynthesis and release by Nrf2-expressing glia potently protects neurons romoxidative stress[J]. J Neurosci,2003,23(8):3394-3406
[12]Gong P, Stewart D, Hu, B, et al. Activation of the mouse heme oxygenase-1 gene by 15-deoxy-Delta (12,14)-prostaglandin J(2) is mediated by the stress response elements and transcription factor Nrf2[J]. Antioxid Redox Signal. 2002,4(2):249-257.
[13]Kraft AD, Lee JM, Johnson DA, et al. Neuronal sensitivityto kainic acid is dependent on the Nrf2-mediated actions of the antioxidant response element [J]. Journal of Neurochemistry,2006,98:1852-1865.
[14]童海达,王佳茗,宋英Keapl-Nrf2-ARE在机体氧化应激损伤中的防御作用[J].癌变.畸变.突变,2013,25(1)：71-75.
[15]甘露,袁萱,张红,等Nrf2/Keap1抗氧化系统与缺血性脑病[J].农垦医学,2011,33(1):79-82.
[16]Li W, Jain MR, Chen C, et al. Nrf2 Possesses a redox-insensitive nuclear export signal overlapping with the leucine zipper motif[J]. J Biol Chem, 2005,280(31):28430-28438.
[17]Kobayashi A, Ohta T, Yamamoto M. Unique function of theNrf2-Keap 1 pathway in the inducible expression of antioxidant and detoxifying enzymes [J]. Methods Enzymol,2004,(378):273-286.
[18]Kraft AD, Lee JM, Johnson DA, et al. Neuronal sensitivityto kainic acid is dependent on theNrf2-mediated actions of the antioxidant response element [J]. Journal of Neurochemistry,2006,98(6):1852-1865.
[19]Zhang DD. Mechanistic studies of the Nrf2-Keap1 signaling pathway[J]. Drug Metab Rev,2006,38(4):769-789.
[20]朱凤臣,蒋电明.Nrf2/ARE转导通路在中枢神经系统疾病中作用的研究进展[J].中国生物制品学杂志,2011,24(6)：741-744.
[21]Jeong WS, Keum YS, Chen C, et al. Differential expression and stability of endogenous nuclear factor E2-related factor Nrf2 by natural chemopreven-tive compounds in HepG2 human hepatoma cells[J]. J Biochem Mol Biol, 2005,38(2):167-176.
[22]钟敏.Nrf2-Keap1抗氧化系统研究进展[J].中国公共卫生,2006,22(3)：360-362.