补肾醒脑方对血管性痴呆模型大鼠炎性反应调控研究
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摘要
目的：通过复制反复性缺血再灌注VD模型,观测补肾醒脑方(BSXNP)对血管性痴呆(VD)模型大鼠学习记忆、脑组织病理形态学,脑组织炎性细胞因子TNF-α、IL-1β、IL-10、TGF-β,黏附分子ICAM-1、VCAM-1. P-selectin、E-selectin,胆碱能抗炎通路中CHAT、AchE与炎症因子的关系及NF-K B变化的影响,研究BSXNP对VD模型大鼠炎性反应的调控作用,进一步探讨BSXNP防治VD的作用机理。
方法：
第一部分：BSXNP对VD模型大鼠行为学及脑组织病理形态学的影响
实验以反复缺血再灌注致VD模型大鼠为研究对象,以喜得镇组为对照组,将雄性Wistar大鼠随机分为模型组(MX)、假手术组(JS)、喜得镇组(XD)补肾醒脑方组(BX),用跳台法、水迷宫法分别于术后第7d、15d、30d观察各组大鼠学习记忆能力；于行为学实验结束后第二天,断头取大鼠脑组织,经HE染色观察各组大鼠脑组织病理形态学变化。
第二部分：BSXNP对VD模型大鼠炎性反应的阻抑作用
实验以反复缺血再灌注致VD模型大鼠为研究对象,以喜得镇组为对照组,将雄性Wistar大鼠随机分为MX、JS、XD、BX,于术后24小时取脑组织,运用ELISA法检测炎性细胞因子TNF-α、IL-1β、IL-10、TGF-β,黏附分子ICAM-1、VCAM-1、P-selectin、E-selectin含量,运用比色法检测CHAT、AchE活力,运用蛋白印迹法检测NF-κB表达。
结果：
第一部分：BSXNP对VD模型大鼠行为学及脑组织病理形态学的影响
1.BSXNP能明显改善VD模型大鼠的学习记忆能力。BSXNP能明显缩短VD模型大鼠不同时间段跳台实验中触电反应期,延长触电潜伏期(P<0.01)；同时均可明显减少VD模型大鼠不同时间段学习和记忆成绩中的错误反应次数(P<0.01)；还可缩短VD模型大鼠在Morris水迷宫中寻找平台潜伏期,增加跨越平台次数(P<0.01或P<0.05)。且BSXNP组明显优于喜德镇组,差异具有统计学意义(P<0.05)。
2.BSXNP能明显改善或减轻VD模型大鼠脑组织神经元的损伤,对脑神经细胞具有保护作用。
第二部分：BSXNP对VD模型大鼠炎性反应的阻抑作用
1.BSXNP能显著降低VD模型大鼠脑组织促炎因子TNF-α、IL-1β的含量(P<0.05),明显降低抗炎因子IL-10、TGF-β的含量(P<0.05)。
2.BSXNP能不同程度的降低VD模型大鼠脑组织粘附分子ICAM-1、VCAM-1、E-selectin、P-select in含量(P<0.05或P<0.01),减轻缺血再灌注损伤。
3.BSXNP能够提高VD模型大鼠脑组织ChAT活性(P<0.05),降低脑组织AchE活性(P<0.01),提示其可能亦作用于“迷走神经—胆碱能抗炎通路”,通过缓解VD模型大鼠迷走神经受到的抑制作用,使Ach的合成增多,减轻炎性反应,从而减少脑组织功能受损。
4.BSXNP能抑制脑缺血再灌注后核转录因子-κB的的转录活性,下调NF-κB的表达,阻断炎症反应信号转导通路,减轻炎性损伤。
结论：1.BSXNP能明显改善VD模型大鼠的学习记忆能力,减轻脑组织神经元的损伤,对脑神经细胞具有保护作用。
2.本研究表明,在反复脑缺血再灌注后,炎症因子表达迅速上升,内皮细胞粘附分子增加,胆碱能抗炎通路未激活,核转录因子活化,从而引起脑组织损伤。给予BSXNP能阻断炎性反应信号转导通路,进而减轻炎症损伤。此表明脑缺血再灌注后出现的白细胞与内皮细胞粘附,炎性细胞聚集、浸润,炎症反应加重,微血管拥堵等是其组织病理基础之一；通过调控脑缺血再灌注后早期炎性反应是BSXNP治疗VD的重要作用机理之一,其可能机制是：BSXNP通过阻断NF-κB炎性反应信号转导通路和激活胆碱能抗炎通路,从而共同调节了炎性因子和黏附因子的表达,通过多通路、多靶点、多环节作用于炎症通路而实现调控炎性反应作用的。
Objective:To observe the BSXNP's influence on the relationship between VD model rat learning and memory,a brain biopsy morphology, and brain inflammatory cells factor TNF-α, IL-1β, IL-10, TGF-β, adhesion molecule ICAM-1, VCAM-1, P-selectin,E-selectin, and the influence on the change of the NF-κB; to study the inflammatory response in rats;to have a further discussing of the regulation function mechanism of action BSXNP prevention VD through the copy of repeatability ischemia-reperfusion.
Methods:
The first part:the BSXNP's influence on the VD model of rats brain biopsy ethology and morphological.
The experiment regard the repeated ischemia-reperfusion cause VD rat models as research object, regard the the joy of as control group, the male Wistar rat randomly is divided into model group (MX), jiaShouShu group (JS), XiDeZhen group (XD), Bu Shen Xing Nao Prescription group (BX), using the diving platform method and water maze method to observe the learning and memory capacity of rats in each group after the experiment respectively in the time of postoperative 7d, 15d,30d. On the second day of the finish of the experiment behaviouristics, bufo by rats organization, take each rats HE dyed observation histopathological morphological changes.
Part2:the resistance inhibitory effect of the BSXNP to the inflammatory response of the rat models.
The experiment regard the repeated ischemia-reperfusion cause VD rat models as research object, the joy of as control group, divided the male Wistar rat randomly into MX, JS, XD, BX,24hours after the operation, take out the brain by using ELISA take brain test inflammatory cells factor TNF-α, IL-1β, IL-10, TGF-β, adhesion molecule ICAM-1, VCAM-1, P-selectin E-selectin content, using colorimetric detection CHAT, AchE vigor, use protein imprinting method to detect NF-κB expression.
Results:
The first part:the influence of BSXNP on the VD model of rats brain biopsy ethology and morphological
1. BSXNP can improve obviously the VD model rats learning and memory capacity obviously. BSXNP can shrink the response time of VD rat models in different period of the platform experiment obviously, extended the time of electric shock reaction (P<0.01). In the same time, it can also reduce times of the fault reaction in the learning and remembering grade of the VD rat model in the different period (P<0.01). It can also shorten VD model rat'time of searching platform in the Morris water maze and increase the times of acrossing platforms(P<0.01 or P<0.05). And BSXNP group's obviously superior to the group, starwood a statistically significant difference (P<0.05).
2. BSXNP can significantly improve or mitigate the injury of the VD model rats's neurons organizational and BSXNP has a protective effect of the brain nerve cells.
Part 2:BSXNP has the resistance inhibitory effect on the inflammatory response of the VD rat models.
1. BSXNP can significantly reduce VD model rats organization promote inflammation factors TNF alpha, IL-1βcontent (P< 0.05), decreased the content of anti-inflammatory factor IL-10, TGF-βobviously (P<0.05).
2. BSXNP can reduce VD model rats organization ICAM-1, adhesion molecules VCAM-1, E-selectin, P-selectin content in different degree (P<0.01 or P<0.05), and lighten the injury of the chemia-reperfusion.
3. BSXNP can improve the activity of ChAT of VD model rats (P<0.05), reducing the activity of AchE (P<0.01), suggesting that its may also play a role in the vagus nerve-choline can anti-inflammatory pathways, VD model rats by dampening the vagus nerve, inhibiting effect by increasing, reduce the synthesis of Ach, inflammatory reaction and thereby reducing brain dysfunction.
4. BSXNP can restrain nuclear transcription factors-κB transcription of activity after the brain ischemia reperfusion, reduce NF-κB expression, blocking inflammation, relieve signal transduction pathways inflammatory lesions.
Conclusion:1. BSXNP can obviously improve the VD model rats the ability of learning and memory in, reduce the damage of brain neurons, protectie effect of nerve cells.
2. This study shows that, after the repeated cerebral ischemia and reperfusion, the inflammatory factor expression rising rapidly, endothelial cell adhesion molecules, choline increased, the anti-inflammatory pathways were not be activated, nuclear transcription factors become active and lead to damage of brain. BSXNP be given to pathways which can block the inflammatory reaction signal, and thus can alleviate inflammation damage. This shows that cerebral ischemia reperfusion appeared after the leucocyte and endothelial cell adhesion, inflammatory cell aggregates, infiltration, inflammation is aggravating, such is its organization capillaries congestion through regulation, one of the pathology base after cerebral ischemia and reperfusion BSXNP treatment early inflammatory reaction is one of the important role the mechanism.Its possible mechanism is: BSXNP by blocking NF-κB inflammatory reaction signalling pathways, and activate the choline can anti-inflammatory pathways, thus common adjust inflammatory factor and adhesion factor expression through multiple access, more and more targets, in the role of inflammatory pathways and link to realize regulation of the inflammatory response function.
方法：
第一部分：BSXNP对VD模型大鼠行为学及脑组织病理形态学的影响
实验以反复缺血再灌注致VD模型大鼠为研究对象,以喜得镇组为对照组,将雄性Wistar大鼠随机分为模型组(MX)、假手术组(JS)、喜得镇组(XD)补肾醒脑方组(BX),用跳台法、水迷宫法分别于术后第7d、15d、30d观察各组大鼠学习记忆能力；于行为学实验结束后第二天,断头取大鼠脑组织,经HE染色观察各组大鼠脑组织病理形态学变化。
第二部分：BSXNP对VD模型大鼠炎性反应的阻抑作用
实验以反复缺血再灌注致VD模型大鼠为研究对象,以喜得镇组为对照组,将雄性Wistar大鼠随机分为MX、JS、XD、BX,于术后24小时取脑组织,运用ELISA法检测炎性细胞因子TNF-α、IL-1β、IL-10、TGF-β,黏附分子ICAM-1、VCAM-1、P-selectin、E-selectin含量,运用比色法检测CHAT、AchE活力,运用蛋白印迹法检测NF-κB表达。
结果：
第一部分：BSXNP对VD模型大鼠行为学及脑组织病理形态学的影响
1.BSXNP能明显改善VD模型大鼠的学习记忆能力。BSXNP能明显缩短VD模型大鼠不同时间段跳台实验中触电反应期,延长触电潜伏期(P<0.01)；同时均可明显减少VD模型大鼠不同时间段学习和记忆成绩中的错误反应次数(P<0.01)；还可缩短VD模型大鼠在Morris水迷宫中寻找平台潜伏期,增加跨越平台次数(P<0.01或P<0.05)。且BSXNP组明显优于喜德镇组,差异具有统计学意义(P<0.05)。
2.BSXNP能明显改善或减轻VD模型大鼠脑组织神经元的损伤,对脑神经细胞具有保护作用。
第二部分：BSXNP对VD模型大鼠炎性反应的阻抑作用
1.BSXNP能显著降低VD模型大鼠脑组织促炎因子TNF-α、IL-1β的含量(P<0.05),明显降低抗炎因子IL-10、TGF-β的含量(P<0.05)。
2.BSXNP能不同程度的降低VD模型大鼠脑组织粘附分子ICAM-1、VCAM-1、E-selectin、P-select in含量(P<0.05或P<0.01),减轻缺血再灌注损伤。
3.BSXNP能够提高VD模型大鼠脑组织ChAT活性(P<0.05),降低脑组织AchE活性(P<0.01),提示其可能亦作用于“迷走神经—胆碱能抗炎通路”,通过缓解VD模型大鼠迷走神经受到的抑制作用,使Ach的合成增多,减轻炎性反应,从而减少脑组织功能受损。
4.BSXNP能抑制脑缺血再灌注后核转录因子-κB的的转录活性,下调NF-κB的表达,阻断炎症反应信号转导通路,减轻炎性损伤。
结论：1.BSXNP能明显改善VD模型大鼠的学习记忆能力,减轻脑组织神经元的损伤,对脑神经细胞具有保护作用。
2.本研究表明,在反复脑缺血再灌注后,炎症因子表达迅速上升,内皮细胞粘附分子增加,胆碱能抗炎通路未激活,核转录因子活化,从而引起脑组织损伤。给予BSXNP能阻断炎性反应信号转导通路,进而减轻炎症损伤。此表明脑缺血再灌注后出现的白细胞与内皮细胞粘附,炎性细胞聚集、浸润,炎症反应加重,微血管拥堵等是其组织病理基础之一；通过调控脑缺血再灌注后早期炎性反应是BSXNP治疗VD的重要作用机理之一,其可能机制是：BSXNP通过阻断NF-κB炎性反应信号转导通路和激活胆碱能抗炎通路,从而共同调节了炎性因子和黏附因子的表达,通过多通路、多靶点、多环节作用于炎症通路而实现调控炎性反应作用的。
Objective:To observe the BSXNP's influence on the relationship between VD model rat learning and memory,a brain biopsy morphology, and brain inflammatory cells factor TNF-α, IL-1β, IL-10, TGF-β, adhesion molecule ICAM-1, VCAM-1, P-selectin,E-selectin, and the influence on the change of the NF-κB; to study the inflammatory response in rats;to have a further discussing of the regulation function mechanism of action BSXNP prevention VD through the copy of repeatability ischemia-reperfusion.
Methods:
The first part:the BSXNP's influence on the VD model of rats brain biopsy ethology and morphological.
The experiment regard the repeated ischemia-reperfusion cause VD rat models as research object, regard the the joy of as control group, the male Wistar rat randomly is divided into model group (MX), jiaShouShu group (JS), XiDeZhen group (XD), Bu Shen Xing Nao Prescription group (BX), using the diving platform method and water maze method to observe the learning and memory capacity of rats in each group after the experiment respectively in the time of postoperative 7d, 15d,30d. On the second day of the finish of the experiment behaviouristics, bufo by rats organization, take each rats HE dyed observation histopathological morphological changes.
Part2:the resistance inhibitory effect of the BSXNP to the inflammatory response of the rat models.
The experiment regard the repeated ischemia-reperfusion cause VD rat models as research object, the joy of as control group, divided the male Wistar rat randomly into MX, JS, XD, BX,24hours after the operation, take out the brain by using ELISA take brain test inflammatory cells factor TNF-α, IL-1β, IL-10, TGF-β, adhesion molecule ICAM-1, VCAM-1, P-selectin E-selectin content, using colorimetric detection CHAT, AchE vigor, use protein imprinting method to detect NF-κB expression.
Results:
The first part:the influence of BSXNP on the VD model of rats brain biopsy ethology and morphological
1. BSXNP can improve obviously the VD model rats learning and memory capacity obviously. BSXNP can shrink the response time of VD rat models in different period of the platform experiment obviously, extended the time of electric shock reaction (P<0.01). In the same time, it can also reduce times of the fault reaction in the learning and remembering grade of the VD rat model in the different period (P<0.01). It can also shorten VD model rat'time of searching platform in the Morris water maze and increase the times of acrossing platforms(P<0.01 or P<0.05). And BSXNP group's obviously superior to the group, starwood a statistically significant difference (P<0.05).
2. BSXNP can significantly improve or mitigate the injury of the VD model rats's neurons organizational and BSXNP has a protective effect of the brain nerve cells.
Part 2:BSXNP has the resistance inhibitory effect on the inflammatory response of the VD rat models.
1. BSXNP can significantly reduce VD model rats organization promote inflammation factors TNF alpha, IL-1βcontent (P< 0.05), decreased the content of anti-inflammatory factor IL-10, TGF-βobviously (P<0.05).
2. BSXNP can reduce VD model rats organization ICAM-1, adhesion molecules VCAM-1, E-selectin, P-selectin content in different degree (P<0.01 or P<0.05), and lighten the injury of the chemia-reperfusion.
3. BSXNP can improve the activity of ChAT of VD model rats (P<0.05), reducing the activity of AchE (P<0.01), suggesting that its may also play a role in the vagus nerve-choline can anti-inflammatory pathways, VD model rats by dampening the vagus nerve, inhibiting effect by increasing, reduce the synthesis of Ach, inflammatory reaction and thereby reducing brain dysfunction.
4. BSXNP can restrain nuclear transcription factors-κB transcription of activity after the brain ischemia reperfusion, reduce NF-κB expression, blocking inflammation, relieve signal transduction pathways inflammatory lesions.
Conclusion:1. BSXNP can obviously improve the VD model rats the ability of learning and memory in, reduce the damage of brain neurons, protectie effect of nerve cells.
2. This study shows that, after the repeated cerebral ischemia and reperfusion, the inflammatory factor expression rising rapidly, endothelial cell adhesion molecules, choline increased, the anti-inflammatory pathways were not be activated, nuclear transcription factors become active and lead to damage of brain. BSXNP be given to pathways which can block the inflammatory reaction signal, and thus can alleviate inflammation damage. This shows that cerebral ischemia reperfusion appeared after the leucocyte and endothelial cell adhesion, inflammatory cell aggregates, infiltration, inflammation is aggravating, such is its organization capillaries congestion through regulation, one of the pathology base after cerebral ischemia and reperfusion BSXNP treatment early inflammatory reaction is one of the important role the mechanism.Its possible mechanism is: BSXNP by blocking NF-κB inflammatory reaction signalling pathways, and activate the choline can anti-inflammatory pathways, thus common adjust inflammatory factor and adhesion factor expression through multiple access, more and more targets, in the role of inflammatory pathways and link to realize regulation of the inflammatory response function.
引文
[1]封银曼,胡久略,任小巧.补肾醒脑法治疗血管性痴呆的研究现状[J].光明中医,2004,19(3)：28-30
[2]封银曼,郑攀,任小巧.补肾醒脑方对实验性血管性痴呆大鼠脑组织中谷氨酸、Y-氨基丁酸含量的影响[J].中医研究,2004,17(2)：22-24
[3]郑攀,封银曼,郑宏,等.补肾醒脑方对实验性血管性痴呆大鼠脑神经细胞Fas、Bcl-2基因表达的影响[J].河南中医,2006,26(2)：25-27
[4]赵琰,周文泉,涂人顺,等.仙龙胶囊对小鼠学习记忆功能的影响[J].中国中医基础医学杂志,2000,6(6)：375-377
[5]袁世宏,王米渠,金沈锐.金匮肾气丸对“恐伤肾”大鼠臣脑、海马c-fos基因表达的影响.北京中医药大学学报,2001,24(6)：34-36.
[6]宋剑南,刘东远,牛晓红,等.高脂血症与中医痰浊关系的实验研究.中国中医基础医学杂志,1995,1：49.
[7]何华,王桂香,钟士江,等.中风后遗症肾虚痰瘀大鼠模型的建立.中国行为医学科学,2005,14(12)：1124-1126
[8]王蕊,杨秦飞,唐一鹏,等.大鼠拟“血管性痴呆”模型的改进[J].中国病理生理杂志,2000,16(10)：914-916
[9]Bowler TV.Cognition in Stroke Act Neural,2007:90:424-429
[10]王永炎,张伯礼.血管性痴呆现代中医临床与研究[M].北京：人民卫生出版社,2003：49.
[11]Longa Ez, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stroke,1989, 20(1):84-91.
[12]Corey-Bloom J,ThaiLJ,Galasko D,etal. Diagnosisand evaluation of demention. Neurology,1995,45:211-218
[13]张伯礼,王永炎,宫涛,等.血管性痴呆的分期证治[C].中国中医药学会内科脑病专业委员会第七次学术研讨会(广州)论文汇编,2001,7：10-13.
[14]颜德馨,吕立言.老年性痴呆与瘀血的关系[J].辽宁中医杂志,1991,18(8)：37-3815.
[151封银曼,高志卿,姚建平.地黄饮子对痴呆小鼠脑功能及乙酰胆碱酯酶活性的影响CJ].辽宁中医杂志,2002.29(3)：181～183.
[16]夏庆华,路千里.熟地黄药理研究进展.江西中医学院学报,2008,20(6)：96-97
[17]崔瑛,颜正华,侯士良,等.熟地黄对动物学习记忆障碍及中枢氨基酸递质、受体的影响[J].中国中药杂志,2003,9(9)：862-866.
[18]张进,黄进,徐志伟.何首乌补肾作用的相关药理研究进展.中药新药与临床药理,2009,20(5)：496-498
[19]刘丽,李林,赵玲,等.二苯乙烯苷对慢性脑缺血大鼠学习记忆的影响[J].中国药理学与毒理学杂志,2008,22(2)：108—115.
[20]区炳雄.何首乌提取物改善小鼠记忆及对海马C-Jun表达的干预[J].中国临床康复,2006,10(23)：144-145.
[21]靳晓明,董琳,范峰,等.女贞子化学成分与药理作用的研究进展.中医药信息,2008,25(1)：40-42
[22]戴岳,杭秉茜,孟庆玉,等.女贞子的抗炎作用[J].中国中药杂志,1989,14(7)：47-49.
[23]Wang XY, Chen J, Zhang J] r, et al. Efect of ginsenoside Rgl on learning and memory impairment induced by beta-amyloidal peptide (25-35) and its mechanism of action [J]. Acta Pham Sin。2001;36(1):14.
[24]杨国愉.人参皂甙对睡眠剥夺大鼠记忆保持的影响[J].中国心理卫生杂志,2001：15(3)：150-2.
[25]胡明亚.β人参化学成分及药理作用的研究进展.中国中医药咨讯,2010,2(15)：286-287
[26]何延龙,周端,董六一.赤芍总苷对大鼠局灶性脑缺血再灌注损伤的保护效果[J].2006,10(39)：59-61.
[27]莫玉兰.赤芍总苷药理作用研究概况.光明中医,2009,24(4)：782-784.
[28]姚国恩,王景周,陈曼娥.川芎嗪对脑缺血后学习记忆障碍的疗效评价[J].脑与神经疾病杂志,2003,11(2)：83-85.
[29]胡国芬,王建平.川芎嗪的药理作用及临床应用进展[J].中国药物与临床,2006,6(10)：56-68.
[30]农慧,盛庆寿.川芎嗪的实验研究纂要.实用中医内科杂志,2009,23(10)：3-5
[31]耿佃涛.川芎嗪的药理研究及临床应用.中国中医药咨讯,2010,2(12)：252-253
[32]崔桂云,沈霞,张璐等.丹参神经保护作用机制的研究.徐州医学院学报,2002,22(6)：492～493
[33]张金茹.丹参药理作用及临床应用.中国医学杂志,2006,4(8)：443-444
[34]景玉宏,冯慎远,汤晓琴.石菖蒲对学习记忆的影响及突触机制.中国中医基础医学杂志,2002,8(6)：38
[35]陈乐真,屠凌岚.石菖蒲的化学成分与药理研究进展.浙江实用医学,2008,13(3)：222-224
[36]张耀春,王立为.远志提取物对小鼠学习记忆的影响[J].中国新药杂志,2006,15(15)：‘1254—1257.
[37]田枫,姜勇,张阔,等.远志总苷对快速老化模型(SAM-P/8)小鼠学习记忆能力的作用及其机理研究[J].老年医学与保健,2004,10(3)：137-139.
[38]陈勤,曹炎贵,张传惠.远志皂苷对B一淀粉样肽和鹅膏蕈氨酸引起胆碱能系统功能降低的影响[J].药学学报,2002,37(12)：913-917.
[39]孟姝.天麻的药理研究进展[J].临床合理用药,2010,3(6)：119
[40]淘云海.天麻药理研究新进展[J].中国中药杂志,2008,33(1)：108-110.
[41]陶云海.天麻药理研究新进展.中国中药杂志,2008,33(1)：108-109
[42]吴寿荣,程刚,冯岩.冰片药理作用的研究进展.中草药,2001,32(12)1143-1145
[43]奚卉.冰片促进血脑屏障开放机制的探讨.安徽医学,2009,30(6)：696～698
[44]Corey-Bloom J, Thal LJ, Galasko D, et al. Diagnosis and evaluatio of dementia. Neurology,1995,45:211-218
[45]明颖,高维娟.血管性痴呆动物模型的研究进展[J].承德医学院学报,2008,25(1)：96-98
[46]王蕊,杨秦飞,唐一鹏,等.大鼠拟“血管性痴呆”模型的改进[J].中国病理生理杂志,2000,16(10)：914-916
[47]贲长恩.中医科研基本思路和方法.北京：人民卫生出版社,1998,453
[48]胡镜清,温泽淮,赖世隆.Morris水迷宫检测的记忆属性与方法学初探[J].广州中医药大学学报,2000,17(6)：117-119
[49]常颖慧,樊小农,石学敏.HE染色光镜观察法在脑组织形态学研究中的应用[J].辽宁中医杂志,2010,37(5)：777-779
[50]ZhaoShuMin, TangYiPeng, LiuAnLin, Gray relation alanalyzing KHJ for learning and memory imPairment indueed by transient Cerebral ischemia reperfusion in mice[J]. Grey System,1998,10(1):65-75
[51]Kto H, Effeets of repeated nonlethal isehemia on the damage of hippoeamPus in rats [J]. BrainRes,1991,553:238-242
[52]Small DL, Morley P, Buchan AM, et al. Biology of ischemic cerebral cell death. Prog Cardiovasc Dis,1999,42(3):185-207.
[53]Jean WC, Speilman SR, Nussbaum ES, et al. Reperfusion injury after focal cerebral ischemia:the role of inflammation and the therapiuptic horizon. Neurosurgery,1998,43(6):1382-1397.
[54]Rosenberg GA. Ischemic brain edema. Prog Cardiovasc Dis,1999, 42(3):209-216.
[55]Liu T, Clark RK, McDonnell PC, et al. Tumor necrosis factor alpha expression in ischemic neurons. Stroke,1994,25(7):1481-1488.
[56]Zhai QH, Futrell N, Chen FJ, et al.Gene expression of IL-10 in relationship to TNF-alpha, IL-lbeta and IL-2 in the rat brain following middle cerebral artery occlusion. J Neurol Sci,1997, 152(2):119-124.
[57]Sairanen TR, Lindsberg PJ, Brenner M, etal. Global forebrain ischemia results in differential cellular expression of interleukin-1 beta (IL-1 beta)and its receptor at mRNA and protein level. J Cere Blood Flow Metab,1997,17(10):1107-1120.
[58]Gregersen R, Lambertsen K, Finsen B. Microglia and macrophages are the major source of tumor necrosis factor in permanent middle cerebral artery occlusion in mice. [J].J Cereb Blood Flow Metab, 2000,20(1):53-65.
[59]Wang X, Yue TL, White RF, et al. Transforming growth factor-beta 1 exhibits delayed gene ixpression following focal cerebral ischemia:Brain Res Bull,1995,36 (6):607-609.
[60]徐霖,李树浓.杨惠玲等主编.高级病理生理学[M].第二版.北京：科学出版社.2006,21：378-380。
[61]尹静,杨,李俐涛,等.粘附分子与缺血性脑损伤.脑与神经疾病杂志[J]：2007,15(4)：318-320
[62]VemugantiR, Dempsey RJ, Bowen KK. Inhibition of inter-cellula adhesionmolecule-lprotein expression by antisense oligonucle- otides is neuroprotective after transientmiddle cerebral artery occlusion in rat. Stroke,2004,35:179-184.
[63]陈邦国,毛庆菊,孔立红.电针对局灶性脑缺血再灌注大鼠缺血脑区细胞黏附分子表达的影响[J].湖北中医学院学报,2006,8(4)：3-5
[64]Danton GH, Diet rich WD. Inflammatory mechanisms after ischemia and stroke [J]. Stroke,2003,62 (2):127-137
[65]Zhang RL, Chopp M, Zologa C, et al. The temporal p rofiles of ICAM-1 protein and mRNA expression after transient MCA occlusion in the rat[J].Brain Res,1995,682:182-188.
[66]苏红梅,朱广旗,欧阳泠星,等.针刺对大鼠脑缺血再灌注损伤后ICAM-1表达的影响[J].上海针灸杂志,2006,25(12)：30-32
[67]罗成基,裴雪涛主编.造血微环境[M].北京：世界医药出版社,2001：1
[68]司英健,张曦,陈幸华,等.VCAM-1和EGFP双基因共表达重组腺病毒的构建[J].重庆医学,2007,36(17)：1699-1703
[69]张丽慧,魏尔清.ICAM-1、VCAM-1在脑缺血损伤炎症机制中的作用及调控[J].中国药理学通报,2005,21(11)：1281～4
[70]雷万龙,袁群芳,张怀波,等.粘附分子表达和巨噬细胞浸润在缺血皮质和基底节区分布的比较[J].广东解剖学通报,1998,20(2)：9-12
[71]Montaner J, Rovira A, Molina CA et al.Plasmatic level of neuroin flammatory markers predict the extent of diffusion weighted image lesions in hyperacute stroke [J].Cereb Blood Flow Metab,2003, 23(12):1403-7.
[72]苗佳音,梁庆成.E-选择素与脑缺血再灌注损伤[J].国际脑血管病杂志2006,14(11)：855-856
[73]陈志鸿,宋宝辉,巴雪青.选择素及其配体的研究进展[J].国外医学遗传学分册,2005,28(5)：270-274
[74]刘玉珍,韩景献,蒋戈利,等.电针对大鼠脑缺血再灌注模型P-选择素和E-选择素表达影响的实验研究[J].时珍国医国药,2007,18(1)：79-81
[75]SorianoSG, LiptonSA, WangYF, etal. Intercellularadhesion moleculede-fiant mice are less susceptible to cerebral ischemia-reperfusion injury [J]. AnaNeurol,1996,39:618-624
[76]KweiS, StavrakisG, TakahasM,etal. Early adapative response soft hevas-cularwall during venousarte rialization in mice[J]. AmJPathol,2004,164:81-89
[77]张国红,王春霖,吕平,等.大鼠局灶性脑缺血再灌注后不同时间E-选择素、P-选择素和细胞间粘附分子-1的表达[J].中国药理学通报,2005,21(10)：1218～23
[78]Suzuk H, Abe K, Tojo S, et al. Post ischemic expression of P-selectin immunoreactivi ty in rat brain[J]. Neuosci Lett,1997,228:151-154
[79]曾丽莉,刘振国.P-选择素与缺血性脑血管病[J].上海第二医科大学学报,2002,22(2)：182-185
[80]Yao L, Setiadi H, Xia I J, et al. Divergent inducible expression of P-selectin and E-selectin in mice and primates[J].Blood,1999, 94(11):3820-3828
[81]Okada Y, Copeland BR,Mori E, et al.P-selectin and intercelluar adhesion molecules-1 expression after focal brain ischemia reperfusion. Sroke,1994,25:292-211
[82]PavlovvA, wangH, ezuraCJ, etaz.The eholinergie anti-in-Flammatory pathway:a missing link in neuroimmunomodula-
tion.MolMed,2003,9 (5-8):125-134
[83]Bernik TR, Friedman SG, Ochani M, et al. Pharmacological stimulaion of the chol inergic antiinf lammatory pathway. J Exp Med,2002,195: 781-788.
[84]柳垂亮,招伟贤.黄文起.胆碱能性抗炎通路的研究进展[J].国际麻醉学与复苏杂志,2007,28(1)：59-62
[85]Wang. H, Yu M, Ochani M, et al.Nicotinic acetylcholine receptor a7 subunit is an essential regulator of inflammation. Nature,2003, 421:384-388.
[86]ZhangXJ, Yang L, Zhao Q, et a.l Induction of acetyl-cholinesterase expression during apoptosis in various cell types [J]. CellDeath Differ,2002,9(8):790-800.
[87]Duysen EG, Stribley JA, Fry DL, et a.l Rescue of the acetylcholinesterase knockoutmouse by feeding a liquid diet; phenotype of the adult acetylcholinesterase defi-cientmouse [J]. Brain Res Dev Brain Res,2002,137(1):43-54.
[88]王博杰,苏跃.胆碱能抗炎通路的研究进展[J].国际麻醉学与复苏杂 志,2006,27 (4):242-245.
[89]Lyudmila V, Boroviko VA, Svetlana L, et al. Vagus nerve stimu-lation attenuates the systemic inflammatory response to endo-toxin[J]. Nature,2000,405:458-461
[90]Czura CJ, Friedman SG, Tracey KJ.Neural inhibition of inf·lam-mation:the cho linergic anti-inflammatory pathway [J]. J Endo-toxin Res,2003,9(6):409-413
[91]Tracey KJ. The inflammatory reflex [J]. Nature,2002,420:853-859
[92]姚咏明,吕艺.胆碱能抗炎通路的调节作用与应用价值[J].江苏大学学报：医学版,2009,19(2)：93-97.
[93]姚咏明,盛志勇.脓毒症防治学[M].北京：科学技术文献出版社,2008：1.
[94]崔睿.NF-κB与脑缺血缺氧再灌注损伤[J].国外医学·麻醉学与复苏分册,2002;23:264.
[95]Aggarwal BB.Nuclear factor-kappa B:the enemy within [J]. Cancer-Cell,2004;6(3):203.
[96]Piva R, Belardo G, Santoro MG. NF-kappaB:A Stress Regulated Switch for Cell Survival.Antioxid Redox Signal.2006 Mar-Apr;8(3-4): 478-86.
[97]Tmhlar SM, Torpey JW, Komives EA. Regions of Ikappa B alpha that are criticalforitsinhibition of Nr-kappaB. DNA interactionfold upon binding to NF-kappaB[A]. Proc Natl Acad Sci USA,2006,103(50): 18951.18956.
[98]Yaron A, Hatztd A, Davis M, el al. Identification of the receptor component of the Ikappa B alpha ubiquitin ligase[J]. Nature,1998, 396(6711):590-594.
[99]Lentsch AB, Ward PA. Activation and regulation of NF-kappaB during acute inflanmmtion[J]. Clin Chem Lab Med,1999,37(3):205-208.
[100]Boni R, Williams AJ, Mofett JR, et al. Quantiative real-time RTPCR analysis of inflanmaatory gene exp ression associated witI1 ischemia reperfusion brain injure[J]. Cereb Blood How Metab,2002, 22(9):1068,1079.
[101]Perkins ND. The Rel/NF-kappa B family:friend and foe [J]. Trends Bioehem Sei,2000,25(9):434-440.
[102]梁炳松,毕桂南.脑缺血预处理对核因子κB相关炎性反应作用研究.医学综述,2007,13(23)：1761-1762
[103]田代实,王光海,郭国际.核因子B在大鼠脑缺血耐受中的作用及其对细胞问黏附分子1和Bc1-2表达的影响[J].中风与神经疾病杂志,2004,21(3)：205-208.
[1]唐旭丽.血管性痴呆54例综合护理体会[J].广西中医学院学报,2009,12：(2)：92-93
[2]王艳玲,赵学军.中医药治疗血管性痴呆研究进展[J].世界中西医结合杂志,2007,2(2)：118.
[3]马云枝,周晓卿.血管性痴呆中西医研究现状[J].河南中医学院学报,2003,18(109)：74.
[4]田金洲,韩明向,涂晋文,等.血管性痴呆的诊断、辨证及疗效判定标准[J].北京中医药大学学报,2000,23(5)：16-24.
[5]邓振明,袁应坚.中风痴呆病[J].中国医药报,1991,6(3)：13-16.
[6]张伯礼,王永炎,宫涛,等.血管性痴呆的分期证治[C].中国中医药学会内科脑病专业委员会第七次学术研讨会(广州)论文汇编,2001,7： 10-13.
[7]王永炎,张伯礼.血管性痴呆现代中医临床与研究[M].北京：人民卫生出版社,2003：49.
[8]马云枝.血管性痴呆的论治[J].河南中医,2000,20(4)：1.
[9]张允岭,梅建勋,张伯礼,等.老年期血管性痴呆分期分证探讨[J].中医杂志,2008,49(2)：173-175.
[10]王新陆.脑血辩证[M]北京：中国医药科技出版社,2002：71-76.
[11]卫振华.血管性痴呆病因病机初探[J].山西中医,2005,21(6)：1-
[12]封银曼,胡久略,任小巧.补肾醒脑法治疗血管性痴呆的研究现状[J].光明中医,2004,19(3)：28-30
[13]于存娟,姜林芳,张志凡.血管性痴呆中医辨治体会[J].陕西中医,200526(1)：94-95.
[14]陈桂铭.血管性痴呆中医临床研究[J].中华实用中西医杂志,2004,17(4)：3198-3199.
[15]田德禄,蔡淦.中医内科学[M].上海：上海科学技术出版社,2006：162
[16]封臻,王媛.马云枝教授三期论治血管性痴呆经验撷英[J].中国中医多现代远程教育,2008,6(10)：1156
[17]周文泉.关于老年期痴呆中医药治疗的思考[J].暨南大学学报(医学版)1999,20(6)：14-17.
[18]赵南刚.况时祥.试述肝阳亢盛与血管性痴呆的关系[J].实用中医药杂志,2006,22(3)：174-175.
[19]朱飞奇,王正君,张海燕.王正君治疗血管性痴呆的临床经验[J].中国 中医药信息杂志,2004,11(2)：169.
[20]任绪东,蔡华.血管性痴呆从络病辨证[J].黑龙江中药,2006,35(1)：25-26.
[21]周海哲,李军,李军.脑泰通颗粒治疗血管性痴呆的临床观察[J].辽宁中医杂志,2007,34(2)：176-177.
[22]李灿,钟炳武,何明大.醒脑再造胶囊治疗血管性痴呆临床观察[J].湖南中医药大学学报,2007,27(5)：61-62.
[23]武煦峰.“填精通窍汤”治疗血管性痴呆32例临床观察[J].江苏中医药,2010,42(2)：30-31
[24]黄琳娜,安军明,苏同生,等.头针治疗血管性痴呆随机对照临床研究[J].上海针灸杂志,2010,29(2)：79-81
[25]杨玫英.醒脑开窍针刺法合用补阳还五汤治疗血管性痴呆46例[J].陕西中医,2007,28(2)：203-204.
[26]孟学峰,范晔,薛连峰.调督醒神法针刺治疗血管性痴呆30例[J].中医外治杂志,2009,18(4)：46-48
[27]李俊仙,肖红玲,王霞,等.中药治疗血管性痴呆的实验研究进展[J].中西医结合心脑血管病杂志,2010,8(1)：89-91
[28]封银曼,郑攀,任小巧.补肾醒脑方对实验性血管性痴呆大鼠脑组织中谷氨酸、γ-氨基丁酸含量的影响[J].中医研究,2004,17(2)：22-24
[29]郑攀,封银曼,郑宏,等.补肾醒脑方对实验性血管性痴呆大鼠脑神经细胞Fas、Bcl-2基因表达的影响[J].河南中医,2006,26(2)：25-27
[30]龚晓健,张乐多,季晖,等.天麻素抗血管性痴呆作用及其机理[J].中 国天然药物,2008,6(2)：1472—1473.
[31]李长生,王荣霞,李军,等.首乌益智灵对血管性痴呆模型大鼠脑组织SOD活性、MDA含量的影响[J].中国老年学杂志,2007,27(18)：1763-1765.
[32]关建军,姬军风,吴世卫,等.针灸益气活血方对血管性痴呆大鼠突触可塑性的实验研究[J].陕西中医,2008,29(10)：1416-1417
[2]封银曼,郑攀,任小巧.补肾醒脑方对实验性血管性痴呆大鼠脑组织中谷氨酸、Y-氨基丁酸含量的影响[J].中医研究,2004,17(2)：22-24
[3]郑攀,封银曼,郑宏,等.补肾醒脑方对实验性血管性痴呆大鼠脑神经细胞Fas、Bcl-2基因表达的影响[J].河南中医,2006,26(2)：25-27
[4]赵琰,周文泉,涂人顺,等.仙龙胶囊对小鼠学习记忆功能的影响[J].中国中医基础医学杂志,2000,6(6)：375-377
[5]袁世宏,王米渠,金沈锐.金匮肾气丸对“恐伤肾”大鼠臣脑、海马c-fos基因表达的影响.北京中医药大学学报,2001,24(6)：34-36.
[6]宋剑南,刘东远,牛晓红,等.高脂血症与中医痰浊关系的实验研究.中国中医基础医学杂志,1995,1：49.
[7]何华,王桂香,钟士江,等.中风后遗症肾虚痰瘀大鼠模型的建立.中国行为医学科学,2005,14(12)：1124-1126
[8]王蕊,杨秦飞,唐一鹏,等.大鼠拟“血管性痴呆”模型的改进[J].中国病理生理杂志,2000,16(10)：914-916
[9]Bowler TV.Cognition in Stroke Act Neural,2007:90:424-429
[10]王永炎,张伯礼.血管性痴呆现代中医临床与研究[M].北京：人民卫生出版社,2003：49.
[11]Longa Ez, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stroke,1989, 20(1):84-91.
[12]Corey-Bloom J,ThaiLJ,Galasko D,etal. Diagnosisand evaluation of demention. Neurology,1995,45:211-218
[13]张伯礼,王永炎,宫涛,等.血管性痴呆的分期证治[C].中国中医药学会内科脑病专业委员会第七次学术研讨会(广州)论文汇编,2001,7：10-13.
[14]颜德馨,吕立言.老年性痴呆与瘀血的关系[J].辽宁中医杂志,1991,18(8)：37-3815.
[151封银曼,高志卿,姚建平.地黄饮子对痴呆小鼠脑功能及乙酰胆碱酯酶活性的影响CJ].辽宁中医杂志,2002.29(3)：181～183.
[16]夏庆华,路千里.熟地黄药理研究进展.江西中医学院学报,2008,20(6)：96-97
[17]崔瑛,颜正华,侯士良,等.熟地黄对动物学习记忆障碍及中枢氨基酸递质、受体的影响[J].中国中药杂志,2003,9(9)：862-866.
[18]张进,黄进,徐志伟.何首乌补肾作用的相关药理研究进展.中药新药与临床药理,2009,20(5)：496-498
[19]刘丽,李林,赵玲,等.二苯乙烯苷对慢性脑缺血大鼠学习记忆的影响[J].中国药理学与毒理学杂志,2008,22(2)：108—115.
[20]区炳雄.何首乌提取物改善小鼠记忆及对海马C-Jun表达的干预[J].中国临床康复,2006,10(23)：144-145.
[21]靳晓明,董琳,范峰,等.女贞子化学成分与药理作用的研究进展.中医药信息,2008,25(1)：40-42
[22]戴岳,杭秉茜,孟庆玉,等.女贞子的抗炎作用[J].中国中药杂志,1989,14(7)：47-49.
[23]Wang XY, Chen J, Zhang J] r, et al. Efect of ginsenoside Rgl on learning and memory impairment induced by beta-amyloidal peptide (25-35) and its mechanism of action [J]. Acta Pham Sin。2001;36(1):14.
[24]杨国愉.人参皂甙对睡眠剥夺大鼠记忆保持的影响[J].中国心理卫生杂志,2001：15(3)：150-2.
[25]胡明亚.β人参化学成分及药理作用的研究进展.中国中医药咨讯,2010,2(15)：286-287
[26]何延龙,周端,董六一.赤芍总苷对大鼠局灶性脑缺血再灌注损伤的保护效果[J].2006,10(39)：59-61.
[27]莫玉兰.赤芍总苷药理作用研究概况.光明中医,2009,24(4)：782-784.
[28]姚国恩,王景周,陈曼娥.川芎嗪对脑缺血后学习记忆障碍的疗效评价[J].脑与神经疾病杂志,2003,11(2)：83-85.
[29]胡国芬,王建平.川芎嗪的药理作用及临床应用进展[J].中国药物与临床,2006,6(10)：56-68.
[30]农慧,盛庆寿.川芎嗪的实验研究纂要.实用中医内科杂志,2009,23(10)：3-5
[31]耿佃涛.川芎嗪的药理研究及临床应用.中国中医药咨讯,2010,2(12)：252-253
[32]崔桂云,沈霞,张璐等.丹参神经保护作用机制的研究.徐州医学院学报,2002,22(6)：492～493
[33]张金茹.丹参药理作用及临床应用.中国医学杂志,2006,4(8)：443-444
[34]景玉宏,冯慎远,汤晓琴.石菖蒲对学习记忆的影响及突触机制.中国中医基础医学杂志,2002,8(6)：38
[35]陈乐真,屠凌岚.石菖蒲的化学成分与药理研究进展.浙江实用医学,2008,13(3)：222-224
[36]张耀春,王立为.远志提取物对小鼠学习记忆的影响[J].中国新药杂志,2006,15(15)：‘1254—1257.
[37]田枫,姜勇,张阔,等.远志总苷对快速老化模型(SAM-P/8)小鼠学习记忆能力的作用及其机理研究[J].老年医学与保健,2004,10(3)：137-139.
[38]陈勤,曹炎贵,张传惠.远志皂苷对B一淀粉样肽和鹅膏蕈氨酸引起胆碱能系统功能降低的影响[J].药学学报,2002,37(12)：913-917.
[39]孟姝.天麻的药理研究进展[J].临床合理用药,2010,3(6)：119
[40]淘云海.天麻药理研究新进展[J].中国中药杂志,2008,33(1)：108-110.
[41]陶云海.天麻药理研究新进展.中国中药杂志,2008,33(1)：108-109
[42]吴寿荣,程刚,冯岩.冰片药理作用的研究进展.中草药,2001,32(12)1143-1145
[43]奚卉.冰片促进血脑屏障开放机制的探讨.安徽医学,2009,30(6)：696～698
[44]Corey-Bloom J, Thal LJ, Galasko D, et al. Diagnosis and evaluatio of dementia. Neurology,1995,45:211-218
[45]明颖,高维娟.血管性痴呆动物模型的研究进展[J].承德医学院学报,2008,25(1)：96-98
[46]王蕊,杨秦飞,唐一鹏,等.大鼠拟“血管性痴呆”模型的改进[J].中国病理生理杂志,2000,16(10)：914-916
[47]贲长恩.中医科研基本思路和方法.北京：人民卫生出版社,1998,453
[48]胡镜清,温泽淮,赖世隆.Morris水迷宫检测的记忆属性与方法学初探[J].广州中医药大学学报,2000,17(6)：117-119
[49]常颖慧,樊小农,石学敏.HE染色光镜观察法在脑组织形态学研究中的应用[J].辽宁中医杂志,2010,37(5)：777-779
[50]ZhaoShuMin, TangYiPeng, LiuAnLin, Gray relation alanalyzing KHJ for learning and memory imPairment indueed by transient Cerebral ischemia reperfusion in mice[J]. Grey System,1998,10(1):65-75
[51]Kto H, Effeets of repeated nonlethal isehemia on the damage of hippoeamPus in rats [J]. BrainRes,1991,553:238-242
[52]Small DL, Morley P, Buchan AM, et al. Biology of ischemic cerebral cell death. Prog Cardiovasc Dis,1999,42(3):185-207.
[53]Jean WC, Speilman SR, Nussbaum ES, et al. Reperfusion injury after focal cerebral ischemia:the role of inflammation and the therapiuptic horizon. Neurosurgery,1998,43(6):1382-1397.
[54]Rosenberg GA. Ischemic brain edema. Prog Cardiovasc Dis,1999, 42(3):209-216.
[55]Liu T, Clark RK, McDonnell PC, et al. Tumor necrosis factor alpha expression in ischemic neurons. Stroke,1994,25(7):1481-1488.
[56]Zhai QH, Futrell N, Chen FJ, et al.Gene expression of IL-10 in relationship to TNF-alpha, IL-lbeta and IL-2 in the rat brain following middle cerebral artery occlusion. J Neurol Sci,1997, 152(2):119-124.
[57]Sairanen TR, Lindsberg PJ, Brenner M, etal. Global forebrain ischemia results in differential cellular expression of interleukin-1 beta (IL-1 beta)and its receptor at mRNA and protein level. J Cere Blood Flow Metab,1997,17(10):1107-1120.
[58]Gregersen R, Lambertsen K, Finsen B. Microglia and macrophages are the major source of tumor necrosis factor in permanent middle cerebral artery occlusion in mice. [J].J Cereb Blood Flow Metab, 2000,20(1):53-65.
[59]Wang X, Yue TL, White RF, et al. Transforming growth factor-beta 1 exhibits delayed gene ixpression following focal cerebral ischemia:Brain Res Bull,1995,36 (6):607-609.
[60]徐霖,李树浓.杨惠玲等主编.高级病理生理学[M].第二版.北京：科学出版社.2006,21：378-380。
[61]尹静,杨,李俐涛,等.粘附分子与缺血性脑损伤.脑与神经疾病杂志[J]：2007,15(4)：318-320
[62]VemugantiR, Dempsey RJ, Bowen KK. Inhibition of inter-cellula adhesionmolecule-lprotein expression by antisense oligonucle- otides is neuroprotective after transientmiddle cerebral artery occlusion in rat. Stroke,2004,35:179-184.
[63]陈邦国,毛庆菊,孔立红.电针对局灶性脑缺血再灌注大鼠缺血脑区细胞黏附分子表达的影响[J].湖北中医学院学报,2006,8(4)：3-5
[64]Danton GH, Diet rich WD. Inflammatory mechanisms after ischemia and stroke [J]. Stroke,2003,62 (2):127-137
[65]Zhang RL, Chopp M, Zologa C, et al. The temporal p rofiles of ICAM-1 protein and mRNA expression after transient MCA occlusion in the rat[J].Brain Res,1995,682:182-188.
[66]苏红梅,朱广旗,欧阳泠星,等.针刺对大鼠脑缺血再灌注损伤后ICAM-1表达的影响[J].上海针灸杂志,2006,25(12)：30-32
[67]罗成基,裴雪涛主编.造血微环境[M].北京：世界医药出版社,2001：1
[68]司英健,张曦,陈幸华,等.VCAM-1和EGFP双基因共表达重组腺病毒的构建[J].重庆医学,2007,36(17)：1699-1703
[69]张丽慧,魏尔清.ICAM-1、VCAM-1在脑缺血损伤炎症机制中的作用及调控[J].中国药理学通报,2005,21(11)：1281～4
[70]雷万龙,袁群芳,张怀波,等.粘附分子表达和巨噬细胞浸润在缺血皮质和基底节区分布的比较[J].广东解剖学通报,1998,20(2)：9-12
[71]Montaner J, Rovira A, Molina CA et al.Plasmatic level of neuroin flammatory markers predict the extent of diffusion weighted image lesions in hyperacute stroke [J].Cereb Blood Flow Metab,2003, 23(12):1403-7.
[72]苗佳音,梁庆成.E-选择素与脑缺血再灌注损伤[J].国际脑血管病杂志2006,14(11)：855-856
[73]陈志鸿,宋宝辉,巴雪青.选择素及其配体的研究进展[J].国外医学遗传学分册,2005,28(5)：270-274
[74]刘玉珍,韩景献,蒋戈利,等.电针对大鼠脑缺血再灌注模型P-选择素和E-选择素表达影响的实验研究[J].时珍国医国药,2007,18(1)：79-81
[75]SorianoSG, LiptonSA, WangYF, etal. Intercellularadhesion moleculede-fiant mice are less susceptible to cerebral ischemia-reperfusion injury [J]. AnaNeurol,1996,39:618-624
[76]KweiS, StavrakisG, TakahasM,etal. Early adapative response soft hevas-cularwall during venousarte rialization in mice[J]. AmJPathol,2004,164:81-89
[77]张国红,王春霖,吕平,等.大鼠局灶性脑缺血再灌注后不同时间E-选择素、P-选择素和细胞间粘附分子-1的表达[J].中国药理学通报,2005,21(10)：1218～23
[78]Suzuk H, Abe K, Tojo S, et al. Post ischemic expression of P-selectin immunoreactivi ty in rat brain[J]. Neuosci Lett,1997,228:151-154
[79]曾丽莉,刘振国.P-选择素与缺血性脑血管病[J].上海第二医科大学学报,2002,22(2)：182-185
[80]Yao L, Setiadi H, Xia I J, et al. Divergent inducible expression of P-selectin and E-selectin in mice and primates[J].Blood,1999, 94(11):3820-3828
[81]Okada Y, Copeland BR,Mori E, et al.P-selectin and intercelluar adhesion molecules-1 expression after focal brain ischemia reperfusion. Sroke,1994,25:292-211
[82]PavlovvA, wangH, ezuraCJ, etaz.The eholinergie anti-in-Flammatory pathway:a missing link in neuroimmunomodula-
tion.MolMed,2003,9 (5-8):125-134
[83]Bernik TR, Friedman SG, Ochani M, et al. Pharmacological stimulaion of the chol inergic antiinf lammatory pathway. J Exp Med,2002,195: 781-788.
[84]柳垂亮,招伟贤.黄文起.胆碱能性抗炎通路的研究进展[J].国际麻醉学与复苏杂志,2007,28(1)：59-62
[85]Wang. H, Yu M, Ochani M, et al.Nicotinic acetylcholine receptor a7 subunit is an essential regulator of inflammation. Nature,2003, 421:384-388.
[86]ZhangXJ, Yang L, Zhao Q, et a.l Induction of acetyl-cholinesterase expression during apoptosis in various cell types [J]. CellDeath Differ,2002,9(8):790-800.
[87]Duysen EG, Stribley JA, Fry DL, et a.l Rescue of the acetylcholinesterase knockoutmouse by feeding a liquid diet; phenotype of the adult acetylcholinesterase defi-cientmouse [J]. Brain Res Dev Brain Res,2002,137(1):43-54.
[88]王博杰,苏跃.胆碱能抗炎通路的研究进展[J].国际麻醉学与复苏杂 志,2006,27 (4):242-245.
[89]Lyudmila V, Boroviko VA, Svetlana L, et al. Vagus nerve stimu-lation attenuates the systemic inflammatory response to endo-toxin[J]. Nature,2000,405:458-461
[90]Czura CJ, Friedman SG, Tracey KJ.Neural inhibition of inf·lam-mation:the cho linergic anti-inflammatory pathway [J]. J Endo-toxin Res,2003,9(6):409-413
[91]Tracey KJ. The inflammatory reflex [J]. Nature,2002,420:853-859
[92]姚咏明,吕艺.胆碱能抗炎通路的调节作用与应用价值[J].江苏大学学报：医学版,2009,19(2)：93-97.
[93]姚咏明,盛志勇.脓毒症防治学[M].北京：科学技术文献出版社,2008：1.
[94]崔睿.NF-κB与脑缺血缺氧再灌注损伤[J].国外医学·麻醉学与复苏分册,2002;23:264.
[95]Aggarwal BB.Nuclear factor-kappa B:the enemy within [J]. Cancer-Cell,2004;6(3):203.
[96]Piva R, Belardo G, Santoro MG. NF-kappaB:A Stress Regulated Switch for Cell Survival.Antioxid Redox Signal.2006 Mar-Apr;8(3-4): 478-86.
[97]Tmhlar SM, Torpey JW, Komives EA. Regions of Ikappa B alpha that are criticalforitsinhibition of Nr-kappaB. DNA interactionfold upon binding to NF-kappaB[A]. Proc Natl Acad Sci USA,2006,103(50): 18951.18956.
[98]Yaron A, Hatztd A, Davis M, el al. Identification of the receptor component of the Ikappa B alpha ubiquitin ligase[J]. Nature,1998, 396(6711):590-594.
[99]Lentsch AB, Ward PA. Activation and regulation of NF-kappaB during acute inflanmmtion[J]. Clin Chem Lab Med,1999,37(3):205-208.
[100]Boni R, Williams AJ, Mofett JR, et al. Quantiative real-time RTPCR analysis of inflanmaatory gene exp ression associated witI1 ischemia reperfusion brain injure[J]. Cereb Blood How Metab,2002, 22(9):1068,1079.
[101]Perkins ND. The Rel/NF-kappa B family:friend and foe [J]. Trends Bioehem Sei,2000,25(9):434-440.
[102]梁炳松,毕桂南.脑缺血预处理对核因子κB相关炎性反应作用研究.医学综述,2007,13(23)：1761-1762
[103]田代实,王光海,郭国际.核因子B在大鼠脑缺血耐受中的作用及其对细胞问黏附分子1和Bc1-2表达的影响[J].中风与神经疾病杂志,2004,21(3)：205-208.
[1]唐旭丽.血管性痴呆54例综合护理体会[J].广西中医学院学报,2009,12：(2)：92-93
[2]王艳玲,赵学军.中医药治疗血管性痴呆研究进展[J].世界中西医结合杂志,2007,2(2)：118.
[3]马云枝,周晓卿.血管性痴呆中西医研究现状[J].河南中医学院学报,2003,18(109)：74.
[4]田金洲,韩明向,涂晋文,等.血管性痴呆的诊断、辨证及疗效判定标准[J].北京中医药大学学报,2000,23(5)：16-24.
[5]邓振明,袁应坚.中风痴呆病[J].中国医药报,1991,6(3)：13-16.
[6]张伯礼,王永炎,宫涛,等.血管性痴呆的分期证治[C].中国中医药学会内科脑病专业委员会第七次学术研讨会(广州)论文汇编,2001,7： 10-13.
[7]王永炎,张伯礼.血管性痴呆现代中医临床与研究[M].北京：人民卫生出版社,2003：49.
[8]马云枝.血管性痴呆的论治[J].河南中医,2000,20(4)：1.
[9]张允岭,梅建勋,张伯礼,等.老年期血管性痴呆分期分证探讨[J].中医杂志,2008,49(2)：173-175.
[10]王新陆.脑血辩证[M]北京：中国医药科技出版社,2002：71-76.
[11]卫振华.血管性痴呆病因病机初探[J].山西中医,2005,21(6)：1-
[12]封银曼,胡久略,任小巧.补肾醒脑法治疗血管性痴呆的研究现状[J].光明中医,2004,19(3)：28-30
[13]于存娟,姜林芳,张志凡.血管性痴呆中医辨治体会[J].陕西中医,200526(1)：94-95.
[14]陈桂铭.血管性痴呆中医临床研究[J].中华实用中西医杂志,2004,17(4)：3198-3199.
[15]田德禄,蔡淦.中医内科学[M].上海：上海科学技术出版社,2006：162
[16]封臻,王媛.马云枝教授三期论治血管性痴呆经验撷英[J].中国中医多现代远程教育,2008,6(10)：1156
[17]周文泉.关于老年期痴呆中医药治疗的思考[J].暨南大学学报(医学版)1999,20(6)：14-17.
[18]赵南刚.况时祥.试述肝阳亢盛与血管性痴呆的关系[J].实用中医药杂志,2006,22(3)：174-175.
[19]朱飞奇,王正君,张海燕.王正君治疗血管性痴呆的临床经验[J].中国 中医药信息杂志,2004,11(2)：169.
[20]任绪东,蔡华.血管性痴呆从络病辨证[J].黑龙江中药,2006,35(1)：25-26.
[21]周海哲,李军,李军.脑泰通颗粒治疗血管性痴呆的临床观察[J].辽宁中医杂志,2007,34(2)：176-177.
[22]李灿,钟炳武,何明大.醒脑再造胶囊治疗血管性痴呆临床观察[J].湖南中医药大学学报,2007,27(5)：61-62.
[23]武煦峰.“填精通窍汤”治疗血管性痴呆32例临床观察[J].江苏中医药,2010,42(2)：30-31
[24]黄琳娜,安军明,苏同生,等.头针治疗血管性痴呆随机对照临床研究[J].上海针灸杂志,2010,29(2)：79-81
[25]杨玫英.醒脑开窍针刺法合用补阳还五汤治疗血管性痴呆46例[J].陕西中医,2007,28(2)：203-204.
[26]孟学峰,范晔,薛连峰.调督醒神法针刺治疗血管性痴呆30例[J].中医外治杂志,2009,18(4)：46-48
[27]李俊仙,肖红玲,王霞,等.中药治疗血管性痴呆的实验研究进展[J].中西医结合心脑血管病杂志,2010,8(1)：89-91
[28]封银曼,郑攀,任小巧.补肾醒脑方对实验性血管性痴呆大鼠脑组织中谷氨酸、γ-氨基丁酸含量的影响[J].中医研究,2004,17(2)：22-24
[29]郑攀,封银曼,郑宏,等.补肾醒脑方对实验性血管性痴呆大鼠脑神经细胞Fas、Bcl-2基因表达的影响[J].河南中医,2006,26(2)：25-27
[30]龚晓健,张乐多,季晖,等.天麻素抗血管性痴呆作用及其机理[J].中 国天然药物,2008,6(2)：1472—1473.
[31]李长生,王荣霞,李军,等.首乌益智灵对血管性痴呆模型大鼠脑组织SOD活性、MDA含量的影响[J].中国老年学杂志,2007,27(18)：1763-1765.
[32]关建军,姬军风,吴世卫,等.针灸益气活血方对血管性痴呆大鼠突触可塑性的实验研究[J].陕西中医,2008,29(10)：1416-1417