头针对急性脑缺血再灌注模型大鼠神经元保护机制的研究
|
摘要
头针对急性脑缺血再灌注模型大鼠神经元保护机制的研究缺血性脑血管病是目前严重危害人类健康的疾病,具有高发病率、高死亡率、高致残率的特点。中医药防治中风具有悠久的历史,早在2000多年前的中医经典著作《黄帝内经》中已经有关于中风的病因病机、治疗原则、预防保健等方面的记载,尤其在针灸治疗中风病方面,历代医学著作均有丰富论述。近年来临床研究表明针刺头穴顶颞前斜线、顶颞后斜线能够改善患侧肢体的运动能力,改善患者的神经功能缺损的评分。本项研究采用线栓法制备大鼠大脑中动脉缺血再灌注模型(MCAO),通过电镜、原位杂交、免疫组化、RT-PCR、ELISA等方法系统观察了针刺顶颞前斜线对大脑中动脉缺血再灌注模型大鼠脑损伤的保护作用,并且通过细胞凋亡、凋亡相关基因表达、炎症反应以及超微结构等几个方面探讨针刺抗脑缺血的作用机制,为临床头针治疗缺血性脑血管病提供了科学的实验依据。
实验方法:选择健康清洁SD大鼠,随机分为A组(假手术组)、B组(模型组)、C组(头针组)。参照Longa的改良的线栓方法制作大鼠局灶性脑缺血再灌注(MCAO)模型。应用TTC染色,观察缺血再灌注后24小时梗死体积,缺血再灌注后3、24、72小时神经功能缺损评分;应用TUNEL法观察神经元凋亡;应用免疫组化法观察脑缺血再灌注后各时间点bcl-2、bax基因表达变化;应用ABC-ELISA法检测IL-1β;应用RT-PCR技术观察脑缺血再灌注后各时间点caspase-3mRNA、caspase-8mRNA表达;光镜、电镜观察神经元结构。所有实验数据用均数±标准差(x±s)表示,应用SPSS10.0统计软件进行数据分析。
实验结果:
1、脑梗死体积。A组未发现梗死灶,B组梗死灶在额、顶叶皮质及尾状核、壳核区域,C组梗死区域小于B组,有统计学意义(P<0.05)。
2、神经功能缺损评分。C组在脑缺血再灌注后3、24、72小时神经功能缺损评分与B组比较均有降低,其中缺血再灌注后24、72小时,C组与B组比较有统计学意义(P<0.01、P<0.05)。
3、神经元凋亡结果。A组可见少量凋亡细胞,B组、C组凋亡细胞主要分布在梗死周围区域,即半暗带区。凋亡细胞在再灌注后3小时开始增加,24小时达高峰,72小时凋亡细胞数减少;B组、C组缺血再灌注后各时间点凋亡细胞与A组比较有显著性差异(P<0.01);C组缺血再灌注后各时间点凋亡细胞与B组比较,显著减少(P<0.01、P<0.05)。
4、免疫组化结果。A组可见少量bcl-2、bax基因表达,B组、C组bcl-2、bax基因表达在半暗带区。bcl-2、bax基因表达在缺血再灌注后3小时开始增强,24小时达高峰,bcl-2高峰表达持续至72小时,bax表达在再灌注后72小时稍有下降;C组再灌注后各时间点bcl-2表达增强,bax表达下降,与B组比较有统计学差异。
5、ABC-ELISA法检测IL-1β。A组IL-1β在大脑皮质少量表达,B组在再灌注早期IL-1β大量出现,72小时达到高峰,C组在各时间点IL-1β显著下降,与B组比较有显著性差异。
6、RT-PCR结果。A组caspase-3mRNA、caspase-8mRNA仅见微弱表达,B组caspase-3mRNA、caspase-8mRNA随着缺血再灌注时间延长,表达逐渐增强,再灌注后24小时表达达到高峰,以后逐渐减弱,C组各时间点caspase-3mRNA、caspase-8mRNA表达与B组比较显著降低。
7、超微结构变化。A组神经元、神经胶质细胞以及毛细血管结构完整,B组神经元细胞质内可见大量空泡样变,细胞器消失;胶质细胞胞质内大量空泡样改变;毛细血管管腔变小,血管内皮细胞增大。C组半暗带区大脑皮质神经元细胞胞质内空泡变少,细胞器较丰富,可见粗面内质网、线粒体、核糖体等,核大,染色质较均匀;胶质细胞胞质内粗面内质网轻度扩张,高尔基体增多;毛细血管管腔变大,内皮光滑。
结论:
第一、针刺头穴能够改善MCAO大鼠神经功能缺损评分,对保持缺血区神经元结构和功能的完整具有重要作用。
第二、针刺头穴能够减少MCAO大鼠缺血区神经细胞凋亡数量。
第三、针刺头穴能够上调MCAO大鼠缺血区bcl-2表达,下调bax表达。
第四、针刺头穴能够抑制MCAO大鼠缺血区炎症反应,下调白介素1β表达。
第五、针刺头穴能够抑制凋亡启动因子caspase-3、caspase-8,从而抑制细胞凋亡。
本项研究表明针刺头穴能够从神经细胞超微结构、细胞凋亡、炎症反应等方面证实头穴针刺能够对MCAO所致脑损伤有保护作用,为临床推广和普及头针疗法以及深入研究提供实验依据。
Preface:Nowdays the ischemia cerebral vascular disease has threatened the health of human being. The ischemia vascular disease has the character of high morbidity, high mortality rate and high cripples rate. Chinese medicine has long history of preventing and controlling stroke. The Chinese medicine classic work《the yellow Emperor Canon of Internal Medicine》has the record of cause, treatment principle and Prevention health care for stroke. Especially acupuncture were used to treat stroke. Recently Clinical researches demonstrate that puncturing the skull point can improve moving ability of the paralytic limb and make the scale of the patient neurology dysfunction better. The MCAO rats were adopted in this research and the technology of TUNEL、RT-PCR、ELISA、immunohistochemistry and electron-microscope were used. the preventing effect of puncturing the head point were observed systematically and the mechanism of the acupuncture anti cerebral ischemia were probed through the cell apoptosis, the express of the associated apoptotic gene, inflammation reaction and neuronal micro structure. This research had provided the scientific evidence for the head needle treating the ischemia cerebral vascular disease clinically.
Materials and Methods:The health rats were randomly divided into 3 groups. A group(sham-operated group);B group(ischemia/reperfusion group);C group (acupuncture treatment group). The middle cerebral artery occlulsion(MCAO) were established by using the longas method. The infarct volume were studied by TTC staining after 24 hours of ischemia and reperfusion, scores of neurological functions deficits were evaluated after 3h、24h、72h following ischemia /reperfusion, neuronal apoptosis were detected by the TUNEL staining, the expression of bcl-2 and bax were observed by immunohistochemistry after 3h、24h、72h following ischemia /reperfusion, the IL-1βwas detected by using the ELISA method, the expression of caspase-3mRNA、caspase-8mRNA were detected by RT-PCR methods, the neural micro structure was observed by electron microscope. All data were expressed as mean±SD. Statistical analysis were carried out by spss10.0.
Results:
1、Infarct volumes
There were not infarcts volume in A group. The infarcts in B、C group were mainly in frontal-parietal cortex, caudates nucleus and putamen nucleus. The infarcts volumes of C group were significantly less than B group(P<0.05)
2、Evaluation of neurological functions deficits Scores of neurological functions deficits of C group were less than that of B group after 3h、24h、72h following ischemia/reperfusion. Compared with the Scores of neurological functions of B group, the difference between C group and B group is significant after 24h、72h following ischemia/reperfusion.
3、Neuronal apoptosis
Apoptotic neurons were mainly located around ischemic tissues, that was ischemic penumbra. There were few apoptotic neuronal cells in A group. The numbers of apoptotic cell increased after 3h following cerebral ischemia/reperfusion, then gradually increased as time went on, at 24h reached the peak, then decreased gradually. The number of apoptotic neuronal cells in A group were different from them in both B and C group significantly. The number of apoptotic neuronal cells in C group is significant less than that in C group(p<0.01,P<0.05)
4、Immunohistochemistry
There were a few expression in A group. The expression of B and C group were mainly located in ischemic penumbra. The expression of bcl-2 and bax began to increase after 3h following cerebral ischemia/reperfusion, reached the peak at 24h, the peak of bcl-2 continuing to 72h following cerebral ischemia/reperfusion, the expression of bax began to decrease after 72h following cerebral ischemia. The expression of bcl-2 in C group is significantly enhanced than that in B group, the expression of bax in C group is weaker than that in B group.
5、Elisa
There were a few IL-1βin A group. IL-1βbegan to increase after 3h following cerebral ischemia/reperfusion, reached the peak at 72h. the number of IL-1βin C group is less than that in B group significantly.
6、Reverse transcription-polymerase chain reaction (RT-PCR)
There were a little expression of caspase-3mRNA and caspase-8 mRNA. The expression of caspase-3mRNA and caspase-8 mRNA gradually increased as time went on following ischemia/reperfusion, reached the peak at 24h following cerebral ischemia/reperfusion. The expression of caspase-3mRNA and caspase-8 mRNA in D group is less than that in B group significantly.
7、Electron-microscope
The neurons、gliocyte and structure of capillaries were in integrity in A group. There were a lot of vacuole in neuron and organelle disappeared in B group. There were also a lot of vacuole in gliocyte and the cavity of capillaries became smaller, vascular endotheliocyte became bigger in B group. In C group there were a few vacuole and a lot of organelle such as endoplasmic reticulum、mitochondria、ribosomes, nucleus was big and chromatin was uniform in neuron; endoplasmic reticulum was expansion mildly, the number of golgi body became more in gliocyte; the cavity of capillaries became bigger and endotheliocyte became smooth.
Conclusion:
1、Acupuncturing the head point-line of anterior oblique line of vertex-teporal and posterior oblique line of vertex-teporal can improve the scores of neurological functions deficits, decrease the infarct volume and make the structure of neuron keeping integrity significantly. this result indicate that acupuncturing the head point have protective effect on cerebral ischemia/reperfusion.
2、Acupuncturing the head point has the protective effect on cerebral ischemia/reperfusion by decreasing neuronal apoptosis in ischemia penumbra.
3、Acupuncturing the head point can significantly increase bcl-2 and decrease bax
4、Acupuncturing the head point can reduce inflammation reaction, lower IL-1βof ischemic penumbra.
5、Acupuncturing the head point can significantly decrease the expressions of caspase-3mRNA and caspase-8 mRNA following cerebral ischemia/reperfusion and inhibit the neuronal apoptosis.
实验方法:选择健康清洁SD大鼠,随机分为A组(假手术组)、B组(模型组)、C组(头针组)。参照Longa的改良的线栓方法制作大鼠局灶性脑缺血再灌注(MCAO)模型。应用TTC染色,观察缺血再灌注后24小时梗死体积,缺血再灌注后3、24、72小时神经功能缺损评分;应用TUNEL法观察神经元凋亡;应用免疫组化法观察脑缺血再灌注后各时间点bcl-2、bax基因表达变化;应用ABC-ELISA法检测IL-1β;应用RT-PCR技术观察脑缺血再灌注后各时间点caspase-3mRNA、caspase-8mRNA表达;光镜、电镜观察神经元结构。所有实验数据用均数±标准差(x±s)表示,应用SPSS10.0统计软件进行数据分析。
实验结果:
1、脑梗死体积。A组未发现梗死灶,B组梗死灶在额、顶叶皮质及尾状核、壳核区域,C组梗死区域小于B组,有统计学意义(P<0.05)。
2、神经功能缺损评分。C组在脑缺血再灌注后3、24、72小时神经功能缺损评分与B组比较均有降低,其中缺血再灌注后24、72小时,C组与B组比较有统计学意义(P<0.01、P<0.05)。
3、神经元凋亡结果。A组可见少量凋亡细胞,B组、C组凋亡细胞主要分布在梗死周围区域,即半暗带区。凋亡细胞在再灌注后3小时开始增加,24小时达高峰,72小时凋亡细胞数减少;B组、C组缺血再灌注后各时间点凋亡细胞与A组比较有显著性差异(P<0.01);C组缺血再灌注后各时间点凋亡细胞与B组比较,显著减少(P<0.01、P<0.05)。
4、免疫组化结果。A组可见少量bcl-2、bax基因表达,B组、C组bcl-2、bax基因表达在半暗带区。bcl-2、bax基因表达在缺血再灌注后3小时开始增强,24小时达高峰,bcl-2高峰表达持续至72小时,bax表达在再灌注后72小时稍有下降;C组再灌注后各时间点bcl-2表达增强,bax表达下降,与B组比较有统计学差异。
5、ABC-ELISA法检测IL-1β。A组IL-1β在大脑皮质少量表达,B组在再灌注早期IL-1β大量出现,72小时达到高峰,C组在各时间点IL-1β显著下降,与B组比较有显著性差异。
6、RT-PCR结果。A组caspase-3mRNA、caspase-8mRNA仅见微弱表达,B组caspase-3mRNA、caspase-8mRNA随着缺血再灌注时间延长,表达逐渐增强,再灌注后24小时表达达到高峰,以后逐渐减弱,C组各时间点caspase-3mRNA、caspase-8mRNA表达与B组比较显著降低。
7、超微结构变化。A组神经元、神经胶质细胞以及毛细血管结构完整,B组神经元细胞质内可见大量空泡样变,细胞器消失;胶质细胞胞质内大量空泡样改变;毛细血管管腔变小,血管内皮细胞增大。C组半暗带区大脑皮质神经元细胞胞质内空泡变少,细胞器较丰富,可见粗面内质网、线粒体、核糖体等,核大,染色质较均匀;胶质细胞胞质内粗面内质网轻度扩张,高尔基体增多;毛细血管管腔变大,内皮光滑。
结论:
第一、针刺头穴能够改善MCAO大鼠神经功能缺损评分,对保持缺血区神经元结构和功能的完整具有重要作用。
第二、针刺头穴能够减少MCAO大鼠缺血区神经细胞凋亡数量。
第三、针刺头穴能够上调MCAO大鼠缺血区bcl-2表达,下调bax表达。
第四、针刺头穴能够抑制MCAO大鼠缺血区炎症反应,下调白介素1β表达。
第五、针刺头穴能够抑制凋亡启动因子caspase-3、caspase-8,从而抑制细胞凋亡。
本项研究表明针刺头穴能够从神经细胞超微结构、细胞凋亡、炎症反应等方面证实头穴针刺能够对MCAO所致脑损伤有保护作用,为临床推广和普及头针疗法以及深入研究提供实验依据。
Preface:Nowdays the ischemia cerebral vascular disease has threatened the health of human being. The ischemia vascular disease has the character of high morbidity, high mortality rate and high cripples rate. Chinese medicine has long history of preventing and controlling stroke. The Chinese medicine classic work《the yellow Emperor Canon of Internal Medicine》has the record of cause, treatment principle and Prevention health care for stroke. Especially acupuncture were used to treat stroke. Recently Clinical researches demonstrate that puncturing the skull point can improve moving ability of the paralytic limb and make the scale of the patient neurology dysfunction better. The MCAO rats were adopted in this research and the technology of TUNEL、RT-PCR、ELISA、immunohistochemistry and electron-microscope were used. the preventing effect of puncturing the head point were observed systematically and the mechanism of the acupuncture anti cerebral ischemia were probed through the cell apoptosis, the express of the associated apoptotic gene, inflammation reaction and neuronal micro structure. This research had provided the scientific evidence for the head needle treating the ischemia cerebral vascular disease clinically.
Materials and Methods:The health rats were randomly divided into 3 groups. A group(sham-operated group);B group(ischemia/reperfusion group);C group (acupuncture treatment group). The middle cerebral artery occlulsion(MCAO) were established by using the longas method. The infarct volume were studied by TTC staining after 24 hours of ischemia and reperfusion, scores of neurological functions deficits were evaluated after 3h、24h、72h following ischemia /reperfusion, neuronal apoptosis were detected by the TUNEL staining, the expression of bcl-2 and bax were observed by immunohistochemistry after 3h、24h、72h following ischemia /reperfusion, the IL-1βwas detected by using the ELISA method, the expression of caspase-3mRNA、caspase-8mRNA were detected by RT-PCR methods, the neural micro structure was observed by electron microscope. All data were expressed as mean±SD. Statistical analysis were carried out by spss10.0.
Results:
1、Infarct volumes
There were not infarcts volume in A group. The infarcts in B、C group were mainly in frontal-parietal cortex, caudates nucleus and putamen nucleus. The infarcts volumes of C group were significantly less than B group(P<0.05)
2、Evaluation of neurological functions deficits Scores of neurological functions deficits of C group were less than that of B group after 3h、24h、72h following ischemia/reperfusion. Compared with the Scores of neurological functions of B group, the difference between C group and B group is significant after 24h、72h following ischemia/reperfusion.
3、Neuronal apoptosis
Apoptotic neurons were mainly located around ischemic tissues, that was ischemic penumbra. There were few apoptotic neuronal cells in A group. The numbers of apoptotic cell increased after 3h following cerebral ischemia/reperfusion, then gradually increased as time went on, at 24h reached the peak, then decreased gradually. The number of apoptotic neuronal cells in A group were different from them in both B and C group significantly. The number of apoptotic neuronal cells in C group is significant less than that in C group(p<0.01,P<0.05)
4、Immunohistochemistry
There were a few expression in A group. The expression of B and C group were mainly located in ischemic penumbra. The expression of bcl-2 and bax began to increase after 3h following cerebral ischemia/reperfusion, reached the peak at 24h, the peak of bcl-2 continuing to 72h following cerebral ischemia/reperfusion, the expression of bax began to decrease after 72h following cerebral ischemia. The expression of bcl-2 in C group is significantly enhanced than that in B group, the expression of bax in C group is weaker than that in B group.
5、Elisa
There were a few IL-1βin A group. IL-1βbegan to increase after 3h following cerebral ischemia/reperfusion, reached the peak at 72h. the number of IL-1βin C group is less than that in B group significantly.
6、Reverse transcription-polymerase chain reaction (RT-PCR)
There were a little expression of caspase-3mRNA and caspase-8 mRNA. The expression of caspase-3mRNA and caspase-8 mRNA gradually increased as time went on following ischemia/reperfusion, reached the peak at 24h following cerebral ischemia/reperfusion. The expression of caspase-3mRNA and caspase-8 mRNA in D group is less than that in B group significantly.
7、Electron-microscope
The neurons、gliocyte and structure of capillaries were in integrity in A group. There were a lot of vacuole in neuron and organelle disappeared in B group. There were also a lot of vacuole in gliocyte and the cavity of capillaries became smaller, vascular endotheliocyte became bigger in B group. In C group there were a few vacuole and a lot of organelle such as endoplasmic reticulum、mitochondria、ribosomes, nucleus was big and chromatin was uniform in neuron; endoplasmic reticulum was expansion mildly, the number of golgi body became more in gliocyte; the cavity of capillaries became bigger and endotheliocyte became smooth.
Conclusion:
1、Acupuncturing the head point-line of anterior oblique line of vertex-teporal and posterior oblique line of vertex-teporal can improve the scores of neurological functions deficits, decrease the infarct volume and make the structure of neuron keeping integrity significantly. this result indicate that acupuncturing the head point have protective effect on cerebral ischemia/reperfusion.
2、Acupuncturing the head point has the protective effect on cerebral ischemia/reperfusion by decreasing neuronal apoptosis in ischemia penumbra.
3、Acupuncturing the head point can significantly increase bcl-2 and decrease bax
4、Acupuncturing the head point can reduce inflammation reaction, lower IL-1βof ischemic penumbra.
5、Acupuncturing the head point can significantly decrease the expressions of caspase-3mRNA and caspase-8 mRNA following cerebral ischemia/reperfusion and inhibit the neuronal apoptosis.
引文
[1] Bederson JB, Pitts LH, Tsuji M, et al. Rat middle cerebral artery occlusion evaluation of the model and development of a neurologic examination. Stroke,1986,17(3) 472
[2]华兴邦.大鼠穴位图谱的研制.实验动物与动物实验,1991,(1):1
[3] Koizumi J, Yoshida Y, Nakazawa T, et al. Experimental studies of ischemic brain edama, A new experimental model of cerebral embolism in rats in which recirculation can be introduced in the ischemic area. [J] Stroke, 1986,8(1):1-8
[4] Longa EZ, Weinstein PR, Carlon S, et al. Reversible middle cerebral artery:occlusion without craniotomy in rats.[J].Stroke,1989,20(1):84-91
[5] Tamura A, Gramham DI, McCultoch J et al. Focal cerebral ischemia in the rat : 1.Descripsion of technique and early neuropathological consequences following middle cerebral artery occlusion. J Cereb blood Flow metab.1981,1(1):53
[6] Chen ST, Hsu CY, Hogan EL,et al. A model of focal ischemia stroke in the rat :Reproducible extensive cortical infarction . Stroke,1986,17(4):738
[7] Waston BD, Dietrich WD, Busto R, et al. Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol, 1985,17(5)497
[8] Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectory in rats. Stroke,1989,20(1):84-91.
[9]刘亢丁、苏志强、李毅平,等。实验性局灶性脑缺血再灌注大鼠的模型的改进与评价[J].中风与神经疾病杂志,1997,14(2):87-89
[10]雷新强.针灸治疗中风临床研究进展.中医研究,2000, 13(1):52
[11]赵大贵,穆敬平,头针结合促通技术对脑卒中偏瘫康复疗效的观察。中国针灸,2005,1(25)19-20
[12] Fugl-Meyer AR, Jaasko L, Leyman I, Olsson S, Steglind S. The post stroke hemiplegic patient. I. A method for evaluation of physical performance. Scand J Rehabil Med 1975;7:13-31.
[13]唐胜修,头针为主治疗缺血性中风后遗症的临床研究.上海针灸杂志,2001,20(2):6-7
[14]王立群,头针治疗中风临床观察,上海针灸杂志,1999,18(5):11
[15]江刚辉,李艳慧,陈振虎.CT定位围针法治疗中风失语症临床研究.中国针灸,2001,21(1)15-16
[16]牛文民,李忠仁.CT定位电头针治疗缺血性中风机理研究.上海针灸杂志,2006,25(7),3-4
[17]黄泳,唐安戍,李求实等.头针对正常人和抑郁症患者颞叶葡萄糖代谢的影响.江苏中医药,2004,25(10)49-50
[18] Charriaut-Marlangue C,Margall I,Reprosa A, et al.Apotosis and necrosis after reversible focal ischemia in and in situ DNA fragmentation analysis [J].J cereb blood flow metab,1996,16(1):186-194
[19] Fujikawa DG.. Confusion between neuronal apoptosis and activation ofprogrammed cell death mechanism acute necrotic results. Trend Neurosci,2000, 23(9):410-411
[20] Honig HS, Rosenberg RN. Apoptisis and neurologic disease. Am J Med,2000,108(4)317-330.
[21] MacuManus JP, Hiu IE, Huang ZG, et al. DNA damage consistent with apoptosis in transient focal ischaemic neocortex「J」. Neuroreport.1994 Jan 12;5(4):493-496
[22]蒲传强,郎森阳,吴平,主编.脑血管病学.北京:人民军医出版社,1999.104-125
[23] Nitatori T, Sato N, Waguri S, et al. Delayed neuronal death in the CA1 pyramid cell layer of the gerbil hippocampus following transient ischemia is apoptosis. J neuroscience , 1995;15;1001-1011.
[24] Beiharz EJ, Williams CE, Dragunow, M,et al. Mechanisms of delayed cell death following hypowic-ischemic injury in the immature rat: evidence for apoptosis during selective neuronal loss[J]. Mol Brain Res, 1995, 29(1):101-106
[25]储照虎,吴家幕,刘富东,等.大鼠局灶性恼缺血再灌注损伤神经细胞凋亡及其调控基因的表达[J].临床神经病学杂志,2000,13(3):134.
[26] Jean WC, Spellmen SR, Mussbaum ES,et al. Reperfusion injury after focal cerebral ischemia: the role of inflammation and therapeutic horizon[J]. Neurosurgery, 1998, 43(6):1382-1397
[27] liu-T, Mc-Donnel PC, Young PR, et al. Interleukin- lβmRNA expression in ischemic rat cortex . stroke, 1997, 24:1746
[28] Saito K, Sugama K, Mishida K, et al. Early increase in TNF-a,1L-6 and 1L-1βlevels following transient cerebral ischemia in gerbil. Neurosci Lett, 1996, 206( 23):149
[29]李岚,马学英,夏松青,等.大鼠局灶性脑缺血再灌注模型中1L- lβ的表达及其与白细胞浸润的关系.临床军医杂志,2000,28( 3):1
[30] Rothman SM, Oley JW. Glutamate and the pothophysiologhy of hypoxicischemic brain damage. Ann Neurol,1986,19:105
[31] Ra WX, Rong ZC. Study about the relationship between the Il-1 receptor and the pathogenesis of epilepsies. Epilepsia 1997,38(supple3)191
[32] Siesjo BK. Pathophysiology and treatment of focal cerebral ischemia part 11 mechanism of damage and treatment. J Neurosurg, 1992,77:337
[33] Kaplanski G , Faruarie R , Kaplanski S , et al . Il-1 induce Il-8 secretion from endothelial cells by a juxtreaction mechanism .blood 1994,84.4242
[34]张在强,龙洁.肝素在缺血性卒中的应用前景。国外医学脑血管病分册,2001, 9(1):42
[35] Rothwell NJ , Relton JK .involvement of interleukin-1 lipocortin-1 in ischemic brain damage J. Cerebrovase B Metab Rev,1993,(5):178-198
[36] Zhao H, Yenary MA, Cheng d,et al. Bcl-2 overexpression protests against neuronsloss within the ischemic margin following experimental stroke and inhibits cytochrome c translocation and caspase-3 activity. Neurochem. 2003,85:1026-36.
[37] Tsujimoto Y, Finger L, Yunis J, et al. Cloning of the chromosome breakpoint of neaplastic B cell with the t(14:18) chromosome translocation Science. 1984. 226: 1097.
[38] Cross A, JockelJ, Wei MC, et al. Enforced dimerization of BAX results in its translocation, mitochondrial dysfunction and apoptosis J . EMBO J ,1998,17:3878一3885
[39] Monaghan P, Robertson D, Andrew T, et al. ultrastructural location of bcl-2 protein. J Histochem Cvtochem, 1992, 40: 1819.
[40] Krajewski S, Tanaka S, Takayama S. et al. lnvestigationg of the subcellular distribution of bcl-2 oncoprotein. Cancer Res. 1993.53: 4701.
[41] Kluck RM, B0SSy- Wetzel L, Green DR, et al. The release of cytochrome C from mitochondria: a primary site for bcl-2 regulation of apoptosis. Science, 1997, 275(5303):1132-1136
[42] Chen J, Graham SH, Nakayama M, et , al. Apoptosis repressor genes bcl-2 and bcl-x are expressed in the rat brain following global ischemia. J Cereb blood flow Metab,1997 17 (1): 2-10.
[43] Chen J, Graham SH, Chan PH, et , al. Bcl-2 is expressed in neurons that survive focal ischemia in the rat. Neuroreport, 1995 , 6 (2): 394-398.
[44]吕青,曲玲,王芳,等.蝙蝠葛酚性碱对小鼠脑缺血一再灌注脑组织Bax和Bcl-2蛋白表达的影响J.中草药,2004, 35( 2):185- 187.
[45] Shimizu, Stoll G, Schroeter M, et al. Differential regulation of bax , bcl-2 and bcl-x proteins in focal cortical ischemia in the rat J. Brain patol, 1998, 8(1):49-62
[46] Martinou J, Dubois-Dauphin M, Staple J,et al. Overexpression of bcl-2 in trandgenic mice protects neuron from naturally occurring death and experimental ischemia.[J] Neuron,1994,13:1017-1025
[47] Macmanus JP, Hiu IE, Huang ZG, et al. DNA damage consistent with apoptosis in transint focal ischemic neocortex [J]. Neuroreport 1994 Jan 12; 5(4):493-6
[48] Borner C. Apoptosis without caspase: an inefficient molecular guillotine? Cell death differ,1999,6(6):497-501
[49] Borner C. Apoptosis without Caspases: an inefficient molecular guillotine? cell death differ,1999,6(6):497-501
[50] Stennicke HR, Salvesen GS. Properties of caspases . Biochem Biophys Acta , 1998,1387:17-31
[51]李小明,孙志贤.细胞凋亡中的关键蛋白酶一Caspase-3[J] .国外医学分子生物学分册,1999,21(1):6-9
[52] Nunez G, benedict M A , Hu Y, et al. Caspase: the caspase of the apoptotic pathway. Oncogene,1998,17:3237-3245
[53] Schulze-osthoff K, Ferrrari D, los M, et al. Apoptosis signaling by death receptors. Eur biochem, 1998:254,439-459
[54] Ni B, wu X, su Y, et al. Transient global forebrain ischemia induces a prolonged expression of the caspase-3mRNA in rat hippocampal CA1 pyramidal neurons. J Cereb blood flow Metab,1998,18(3)248-256
[55] Endres M, Namura S, Shimizu-Sasamata M, et al. Attenuation of delayed neuronal death after mild focal ischemia in mice by inhibition of the caspase family. J Cereb blood flow Metab,1998,18(3)238-247
[56] Schulz JB, Weller M, Moskwitz MA. Caspases as treatment targets in stroke and neurodegenerative disease. Ann neural,1999,45:421-429
[1]陈璧琉,郑卓人.灵枢经白话解,北京;人民卫生出版社,1962.524
[2]刘渡舟,苏宝钢.金匾要略设释.天津;天津科学技术出版社,1984.42
[3]孙思邀.千金要方.北京;华夏出版社,1993.122
[4]楼英.医学纲目.北京;人民卫生出版社,1981
[5]周凤梧,王万杰,徐国仟.黄帝内经素问白话解.北京;人民卫生出版社,1958.15
[6]周凤梧,王万杰,徐国仟.黄帝内经素问白话解.北京;人民卫生出版社,1958. 227
[7]刘渡舟,苏宝钢.金匾要略诊释.天津;天津科学技术出版社,1984.43
[8]丁光迪.诸病源候论校注.北京;人民卫生出版社,1992.14
[9]张介宾.景岳全书.北京;人民卫生出版社,1991.222
[10]巢元方等.诸病源候论.北京;人民卫生出版社,1955:2-16
[11]陈自明.妇人大全良方·众疾
[12]王文化赵冬等北京市1984年～1999年人群脑卒中发病率变化趋势分析中华流行病学杂志2001年8月第22卷第4期269～271
[13]方向华汤哲等北京市55岁以上人群1992年和2000年的脑卒中患病率和残疾率情况和变动趋势中华老年心脑血管病杂志2007年1月第9卷第1期32～35
[14]吴志英刘之荣等西北五省区老年人脑中风流行病学中国神经精神疾病杂志1995年第21卷第2期69～71
[15]王维治神经病学(第四版)北京人民卫生出版社2001年9月
[16]徐晓利,马涧泉医学生物化学北京人民卫生出版社,1998 719～723
[17] Siesj,o B.K. Pathophysiology and treatment of focal cerebral ischemia, Part I .Neurosurg,1992, 77:169-I84.
[18]周建伟,肖鸣.头针在中风临床中的应用观察.中国针灸,1999,19(10):635
[19]周飞,李福风,程介士,严振国。电针对急性脑缺血大鼠局部脑血流和脑梗死体积的影响。上海针灸杂志,2003 22 (5)3-6
[20]许能贵,易玮等,电针对大鼠局灶性,脑缺血后神经元损伤保护作用的研究。中国针灸,2000, (4) : 40一42
[21] Kekesi K.A., Szilagyi N., Nyittai G., et al. Persistent depolarization and glu uptake inhibition operate distinct osmoregulatory mechanisms in the mammalian brain.Neurochem. Int,2000,37:171-178
[22]郭景春,程介士。电针脑缺血大鼠纹状体细胞外兴奋性氨基酸含量的影响[J],上海针灸杂志,2000:19(1):37
[23]许能贵,马勤耘,许冠荪,等.电针对局灶性脑缺血.大鼠脑血流量、组织含水量、SOD, MDA的影响[J].中国针灸,1998,23(3):175
[24]任丽民.唐启盛.刘建秋等.针刺时急性脑梗塞病人抗氧自由基酶类影响的观察[J].针灸临床杂志.1995,11(3):13.
[25]陈志强等,电针对脑局部缺血再灌流损伤大鼠自由基的影响[J],中国针灸,1998,( 7 ) : 409
[26]聂卉等,头穴电鍉针对急性脑血管病的抗脂质过氧化作用[J],针灸临床杂志,1999, ( 12 ): 36
[27]王光义,蒋乃昌,贺志光.头针对脑梗塞患者血浆ET-1,MDA,NO的影响[J].中国针灸,2001,21(4):241
[28]李威,范军铭,贾士奇,等.电针对大鼠全脑缺血.再灌流损伤的保护作用[J].中国针灸,1996,16(11):21
[29]吴绪平,周爽,刘又香.等,头穴透刺对急性脑梗塞大鼠血浆中cAMP, cGMP含量的影响[J].中国针灸,2000; 20 ( 11 ): 694
[30]王亚文,刘又香,靳晶,等.头穴透刺对急性脑梗死大鼠脑组织中cAMP , cGMP含量的影响[J]湖北中医学院学报,2001,3(1):17
[31]许贞峰,吴根诚,曹小定.电针对局灶性脑缺血/再灌注大鼠IL-1RamRNA表达的调节[J].针刺研究,2001,26(3):194
[32]张艳玲、李创鹏、马雅玲.中国针灸,针刺治疗急性脑梗塞对TNF-a, IL-6及肌力的影响[J].2001:21(11):677
[33]雷新强等,头针对急性局灶性脑缺血模型大鼠的影响[J],中国中西医结合杂志,1997, ( 9 ): 544
[34]周炜.工丽平.刘泓等.头针对脑梗塞患者血清肿瘤坏死因子的影响[J].上海针灸杂志2002, 21(1):11
[35]许贞峰,吴根诚,曹小定.电针对局灶性脑缺血/再灌注大鼠IL-1RamRNA表达的调节[J].针刺研究,2001,26(3):194
[36]李菁,肖建华,东贵荣.脑出血急性期头针治疗的临床研究[J].中国中西医结合杂志,1999, 19( 4) : 203 -205
[37]张红星,张唐法.头针治疗中风及对血浆内皮素含量的影响[J ].中国针灸,2002, 22( 12) : 831 -832
[38]王宏宝.精制蝮蛇抗栓酶与头针联用治疗恢复期脑梗死疗效观察[J].华中医学杂志,2002, 26( 3) : 139.
[39]刘宁,马国庆,闰子生.头针丛刺长留针治疗缺血性脑梗塞的临床观察[J].针灸临床杂志.2001.17(3):31.
[40]王光义.蒋乃昌.贺志光.头针对脑梗塞患者血浆ET-1 ,MDA ,NO的影响,[J],中国针灸2001, 21( 4) : 241.
[41]施静,刘晓春,张静,等.电针对脑缺血神经元凋亡影响的形态学研究[J].中国组织化学与细胞化学杂志,1998,7(4):391
[42]王利等,电针对大鼠脑局部缺血再灌流后c-fos , mRNA表达的影响[J],中国针灸,2000(4):241
[43]董劲松,陈伯英.即早表达基c-fos在电针抗局灶性脑缺血损伤中作用的研究[J].针刺研究,2001,26(2):97
[44]马岩璠,王舒,鲁斌,等.醒脑开窍针刺法干预实验性脑梗塞大鼠热休克蛋白基因表达的研究[J].中国针灸,2001,21(2):107
[45] Linda J M,Jean Mary.Apoptosis.Science,1998,281(5381):1301.
[46] Kim GW, Nobuo N, Sugawara TK, et al. Early decrease in DNA repair proteins, Ku70 and Ku86, and subsequent DNA fragmentation after transient focal cerebral ischemia in mice. Stroke,2001,32:1401-1407.
[47]储照虎,吴家幂.大鼠局灶性脑缺血再灌注损伤时神经细胞凋亡及其调控基因的表达.Clin Neurol,2000,13(3):134-136.
[48] Nitatori T. Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis.J Neurosei,1995,15(2):1001.
[49] Sei Y.Internucleosomal DNA fragmentation in gerbil hippocampus following forebrain ischemia.Neurosei Lett,1994,171(1-2):179.
[50] Volpe BT. Temporal pattern of internucleosomal DNA fragmentation in the striatum and hippocampus after transient forebrain ischemia. Neurosei Lett,1995,186(2-3):157.
[51] Greco R, Amantea D, Blandini F, et al. Neuroprotective effect of nitroglycerin in a rodent model of ischemic stroke: evaluation of Bcl-2 expression. Int Rev Neurobiol.2007;82;423-35
[52] Zhao H, Yenari MA, Cheng D, et al. Bcl-2 overexpression protects against neuronloss within the ischemic margin following experimental stroke and inhibits cytochrome c translocation and caspase-3 activity.Neurochem, 2003,85:1026-1036.。
[53] Choi JM, Shin HK, Kim KY, et al. Neuroprotective effect of cilostazol against focal cerebral ischemia via antiapoptotic action in rats. JPharmacol Exp Ther, 2002,300:787-793.
[54] Cao G, MinamiM, PeiW, et a.l Intracellular Bax translocation after transient cerebral ischemia: implications for a role of themitochondrial apoptotic signaling pathway in ischemic neuronal death [J]. Cereb Blood FlowMetab, 2001, 21(4): 321-333. (6): 415-419.
[55] Amemiva S, Kamiva T, Nito C, et al. Anti-apoptotic and neuroprotective effects of edaravone following transient focal ischemia in rats. Eur J pharmacol,2005 Jun 1;516(2):125-30
[56] Zhao H, Yenari MA, Cheng D, et al. Bcl-2 overexpression protects against neuron loss within the ischemic margin following experimental stroke and inhibits cytochrome c translocation and caspase-3 activity. Neurochem ,2003 may;85(4):1026-36
[57] Datta SR, KatsovA, Hu L, et al. 14-3-3 proteins and survival kinases cooperate to inactivate Bad byBH3 domain hosphorylation [J]. MolCel,l 2000, 6(1): 41-45.
[58] CaoYJ, Shibata T, Rainov NG. Liposome-mediated transfer of the Bcl-2 gene results in neuroprotection after in vivo transient focal cerebral ischemia in an animalmodel[J].Gene Ther, 2002, 9
[59] Li DQ, Bai AM, Li Y, et al. Catalpol modulates the expressions of Bcl-2 and Bax and attenuates apoptosis in gerbils after ischemic injury. Brain Res. 2006 oct 18;1115(1):179-81
[60]刘富东,许燕.局灶性脑缺血大鼠神经细胞凋亡及其调控基因bcl-2的表达.皖南医学院学报,2001,20(10):6-7.
[61] Nunez G, Benedict MA, Hu Y, et a.l Caspases: the proteases of the apoptotic pathway[ J]. Oncogene, 1998 , 17 (25): 3237 -3245.
[62] Ashkenazi A, Dixit VM. Death receptors: signaling and modulation[J]. Science, 1998, 281(5381): 1305-1308.
[63] Schulz JB, WellerM, MoskowitzMA. Caspases as treatment targets in stroke and neurodegenerative diseases[ J]. Ann Neurol 1999, 45(4): 421-429.
[64] NiB, Wu X, SuY, eta.l Transientglobal forebrain ischemia induces a prolonged expression of the caspase-3 RNA in rat hippocampal CA1 pyramidal neurons[ J]. Cereb Blood Flow Metab,1998, 18(3): 248-256.
[65] Chen J, Nagayama T, Jin K, et a.l Induction of caspase-3-like proteasemaymediate delayed neuronal death in the hippocampus after transient cerebral ischemia[J]. Neurosc,i 1998 , 18(13):4914-4928.
[66] Ferrer I, Friguls B, Dalfo E,et al. Caspase-dependent and caspase-in-dependentsignalling of apoptosis in the penumbra following middle cerebral artery occlusion in the adult rat. Neuropathol Appl Neurobiol,2003,29:472-481.
[67] Lee SH, Kim M, Kim YJ, et al. Ischemic intensity influences the distribution of delayed infarction and apoptotic cell death following transient focal cerebral ischemia in rats. Brain Res,2002, 956:14-23
[68] Ferrer I, Friquls B, Justici C, et al. Caspase-dependent and caspase-independent signalling of apoptosis in the penumbra following middle cerebral artery occlusion in the adult rat. Neuropathol Appl Neurobiol ,2003 10;(29)5:472-81
[69] Zhu HC, Gao XQ, Xing Y, et al. Inhibition of caspase-3 activation and apoptosis is involved in 3-nitropropionic acid-induced ischemic tolerance to transient focal cerebral ischemia in rats. Mol Neurosic 2004;24(2):299-305
[2]华兴邦.大鼠穴位图谱的研制.实验动物与动物实验,1991,(1):1
[3] Koizumi J, Yoshida Y, Nakazawa T, et al. Experimental studies of ischemic brain edama, A new experimental model of cerebral embolism in rats in which recirculation can be introduced in the ischemic area. [J] Stroke, 1986,8(1):1-8
[4] Longa EZ, Weinstein PR, Carlon S, et al. Reversible middle cerebral artery:occlusion without craniotomy in rats.[J].Stroke,1989,20(1):84-91
[5] Tamura A, Gramham DI, McCultoch J et al. Focal cerebral ischemia in the rat : 1.Descripsion of technique and early neuropathological consequences following middle cerebral artery occlusion. J Cereb blood Flow metab.1981,1(1):53
[6] Chen ST, Hsu CY, Hogan EL,et al. A model of focal ischemia stroke in the rat :Reproducible extensive cortical infarction . Stroke,1986,17(4):738
[7] Waston BD, Dietrich WD, Busto R, et al. Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol, 1985,17(5)497
[8] Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectory in rats. Stroke,1989,20(1):84-91.
[9]刘亢丁、苏志强、李毅平,等。实验性局灶性脑缺血再灌注大鼠的模型的改进与评价[J].中风与神经疾病杂志,1997,14(2):87-89
[10]雷新强.针灸治疗中风临床研究进展.中医研究,2000, 13(1):52
[11]赵大贵,穆敬平,头针结合促通技术对脑卒中偏瘫康复疗效的观察。中国针灸,2005,1(25)19-20
[12] Fugl-Meyer AR, Jaasko L, Leyman I, Olsson S, Steglind S. The post stroke hemiplegic patient. I. A method for evaluation of physical performance. Scand J Rehabil Med 1975;7:13-31.
[13]唐胜修,头针为主治疗缺血性中风后遗症的临床研究.上海针灸杂志,2001,20(2):6-7
[14]王立群,头针治疗中风临床观察,上海针灸杂志,1999,18(5):11
[15]江刚辉,李艳慧,陈振虎.CT定位围针法治疗中风失语症临床研究.中国针灸,2001,21(1)15-16
[16]牛文民,李忠仁.CT定位电头针治疗缺血性中风机理研究.上海针灸杂志,2006,25(7),3-4
[17]黄泳,唐安戍,李求实等.头针对正常人和抑郁症患者颞叶葡萄糖代谢的影响.江苏中医药,2004,25(10)49-50
[18] Charriaut-Marlangue C,Margall I,Reprosa A, et al.Apotosis and necrosis after reversible focal ischemia in and in situ DNA fragmentation analysis [J].J cereb blood flow metab,1996,16(1):186-194
[19] Fujikawa DG.. Confusion between neuronal apoptosis and activation ofprogrammed cell death mechanism acute necrotic results. Trend Neurosci,2000, 23(9):410-411
[20] Honig HS, Rosenberg RN. Apoptisis and neurologic disease. Am J Med,2000,108(4)317-330.
[21] MacuManus JP, Hiu IE, Huang ZG, et al. DNA damage consistent with apoptosis in transient focal ischaemic neocortex「J」. Neuroreport.1994 Jan 12;5(4):493-496
[22]蒲传强,郎森阳,吴平,主编.脑血管病学.北京:人民军医出版社,1999.104-125
[23] Nitatori T, Sato N, Waguri S, et al. Delayed neuronal death in the CA1 pyramid cell layer of the gerbil hippocampus following transient ischemia is apoptosis. J neuroscience , 1995;15;1001-1011.
[24] Beiharz EJ, Williams CE, Dragunow, M,et al. Mechanisms of delayed cell death following hypowic-ischemic injury in the immature rat: evidence for apoptosis during selective neuronal loss[J]. Mol Brain Res, 1995, 29(1):101-106
[25]储照虎,吴家幕,刘富东,等.大鼠局灶性恼缺血再灌注损伤神经细胞凋亡及其调控基因的表达[J].临床神经病学杂志,2000,13(3):134.
[26] Jean WC, Spellmen SR, Mussbaum ES,et al. Reperfusion injury after focal cerebral ischemia: the role of inflammation and therapeutic horizon[J]. Neurosurgery, 1998, 43(6):1382-1397
[27] liu-T, Mc-Donnel PC, Young PR, et al. Interleukin- lβmRNA expression in ischemic rat cortex . stroke, 1997, 24:1746
[28] Saito K, Sugama K, Mishida K, et al. Early increase in TNF-a,1L-6 and 1L-1βlevels following transient cerebral ischemia in gerbil. Neurosci Lett, 1996, 206( 23):149
[29]李岚,马学英,夏松青,等.大鼠局灶性脑缺血再灌注模型中1L- lβ的表达及其与白细胞浸润的关系.临床军医杂志,2000,28( 3):1
[30] Rothman SM, Oley JW. Glutamate and the pothophysiologhy of hypoxicischemic brain damage. Ann Neurol,1986,19:105
[31] Ra WX, Rong ZC. Study about the relationship between the Il-1 receptor and the pathogenesis of epilepsies. Epilepsia 1997,38(supple3)191
[32] Siesjo BK. Pathophysiology and treatment of focal cerebral ischemia part 11 mechanism of damage and treatment. J Neurosurg, 1992,77:337
[33] Kaplanski G , Faruarie R , Kaplanski S , et al . Il-1 induce Il-8 secretion from endothelial cells by a juxtreaction mechanism .blood 1994,84.4242
[34]张在强,龙洁.肝素在缺血性卒中的应用前景。国外医学脑血管病分册,2001, 9(1):42
[35] Rothwell NJ , Relton JK .involvement of interleukin-1 lipocortin-1 in ischemic brain damage J. Cerebrovase B Metab Rev,1993,(5):178-198
[36] Zhao H, Yenary MA, Cheng d,et al. Bcl-2 overexpression protests against neuronsloss within the ischemic margin following experimental stroke and inhibits cytochrome c translocation and caspase-3 activity. Neurochem. 2003,85:1026-36.
[37] Tsujimoto Y, Finger L, Yunis J, et al. Cloning of the chromosome breakpoint of neaplastic B cell with the t(14:18) chromosome translocation Science. 1984. 226: 1097.
[38] Cross A, JockelJ, Wei MC, et al. Enforced dimerization of BAX results in its translocation, mitochondrial dysfunction and apoptosis J . EMBO J ,1998,17:3878一3885
[39] Monaghan P, Robertson D, Andrew T, et al. ultrastructural location of bcl-2 protein. J Histochem Cvtochem, 1992, 40: 1819.
[40] Krajewski S, Tanaka S, Takayama S. et al. lnvestigationg of the subcellular distribution of bcl-2 oncoprotein. Cancer Res. 1993.53: 4701.
[41] Kluck RM, B0SSy- Wetzel L, Green DR, et al. The release of cytochrome C from mitochondria: a primary site for bcl-2 regulation of apoptosis. Science, 1997, 275(5303):1132-1136
[42] Chen J, Graham SH, Nakayama M, et , al. Apoptosis repressor genes bcl-2 and bcl-x are expressed in the rat brain following global ischemia. J Cereb blood flow Metab,1997 17 (1): 2-10.
[43] Chen J, Graham SH, Chan PH, et , al. Bcl-2 is expressed in neurons that survive focal ischemia in the rat. Neuroreport, 1995 , 6 (2): 394-398.
[44]吕青,曲玲,王芳,等.蝙蝠葛酚性碱对小鼠脑缺血一再灌注脑组织Bax和Bcl-2蛋白表达的影响J.中草药,2004, 35( 2):185- 187.
[45] Shimizu, Stoll G, Schroeter M, et al. Differential regulation of bax , bcl-2 and bcl-x proteins in focal cortical ischemia in the rat J. Brain patol, 1998, 8(1):49-62
[46] Martinou J, Dubois-Dauphin M, Staple J,et al. Overexpression of bcl-2 in trandgenic mice protects neuron from naturally occurring death and experimental ischemia.[J] Neuron,1994,13:1017-1025
[47] Macmanus JP, Hiu IE, Huang ZG, et al. DNA damage consistent with apoptosis in transint focal ischemic neocortex [J]. Neuroreport 1994 Jan 12; 5(4):493-6
[48] Borner C. Apoptosis without caspase: an inefficient molecular guillotine? Cell death differ,1999,6(6):497-501
[49] Borner C. Apoptosis without Caspases: an inefficient molecular guillotine? cell death differ,1999,6(6):497-501
[50] Stennicke HR, Salvesen GS. Properties of caspases . Biochem Biophys Acta , 1998,1387:17-31
[51]李小明,孙志贤.细胞凋亡中的关键蛋白酶一Caspase-3[J] .国外医学分子生物学分册,1999,21(1):6-9
[52] Nunez G, benedict M A , Hu Y, et al. Caspase: the caspase of the apoptotic pathway. Oncogene,1998,17:3237-3245
[53] Schulze-osthoff K, Ferrrari D, los M, et al. Apoptosis signaling by death receptors. Eur biochem, 1998:254,439-459
[54] Ni B, wu X, su Y, et al. Transient global forebrain ischemia induces a prolonged expression of the caspase-3mRNA in rat hippocampal CA1 pyramidal neurons. J Cereb blood flow Metab,1998,18(3)248-256
[55] Endres M, Namura S, Shimizu-Sasamata M, et al. Attenuation of delayed neuronal death after mild focal ischemia in mice by inhibition of the caspase family. J Cereb blood flow Metab,1998,18(3)238-247
[56] Schulz JB, Weller M, Moskwitz MA. Caspases as treatment targets in stroke and neurodegenerative disease. Ann neural,1999,45:421-429
[1]陈璧琉,郑卓人.灵枢经白话解,北京;人民卫生出版社,1962.524
[2]刘渡舟,苏宝钢.金匾要略设释.天津;天津科学技术出版社,1984.42
[3]孙思邀.千金要方.北京;华夏出版社,1993.122
[4]楼英.医学纲目.北京;人民卫生出版社,1981
[5]周凤梧,王万杰,徐国仟.黄帝内经素问白话解.北京;人民卫生出版社,1958.15
[6]周凤梧,王万杰,徐国仟.黄帝内经素问白话解.北京;人民卫生出版社,1958. 227
[7]刘渡舟,苏宝钢.金匾要略诊释.天津;天津科学技术出版社,1984.43
[8]丁光迪.诸病源候论校注.北京;人民卫生出版社,1992.14
[9]张介宾.景岳全书.北京;人民卫生出版社,1991.222
[10]巢元方等.诸病源候论.北京;人民卫生出版社,1955:2-16
[11]陈自明.妇人大全良方·众疾
[12]王文化赵冬等北京市1984年～1999年人群脑卒中发病率变化趋势分析中华流行病学杂志2001年8月第22卷第4期269～271
[13]方向华汤哲等北京市55岁以上人群1992年和2000年的脑卒中患病率和残疾率情况和变动趋势中华老年心脑血管病杂志2007年1月第9卷第1期32～35
[14]吴志英刘之荣等西北五省区老年人脑中风流行病学中国神经精神疾病杂志1995年第21卷第2期69～71
[15]王维治神经病学(第四版)北京人民卫生出版社2001年9月
[16]徐晓利,马涧泉医学生物化学北京人民卫生出版社,1998 719～723
[17] Siesj,o B.K. Pathophysiology and treatment of focal cerebral ischemia, Part I .Neurosurg,1992, 77:169-I84.
[18]周建伟,肖鸣.头针在中风临床中的应用观察.中国针灸,1999,19(10):635
[19]周飞,李福风,程介士,严振国。电针对急性脑缺血大鼠局部脑血流和脑梗死体积的影响。上海针灸杂志,2003 22 (5)3-6
[20]许能贵,易玮等,电针对大鼠局灶性,脑缺血后神经元损伤保护作用的研究。中国针灸,2000, (4) : 40一42
[21] Kekesi K.A., Szilagyi N., Nyittai G., et al. Persistent depolarization and glu uptake inhibition operate distinct osmoregulatory mechanisms in the mammalian brain.Neurochem. Int,2000,37:171-178
[22]郭景春,程介士。电针脑缺血大鼠纹状体细胞外兴奋性氨基酸含量的影响[J],上海针灸杂志,2000:19(1):37
[23]许能贵,马勤耘,许冠荪,等.电针对局灶性脑缺血.大鼠脑血流量、组织含水量、SOD, MDA的影响[J].中国针灸,1998,23(3):175
[24]任丽民.唐启盛.刘建秋等.针刺时急性脑梗塞病人抗氧自由基酶类影响的观察[J].针灸临床杂志.1995,11(3):13.
[25]陈志强等,电针对脑局部缺血再灌流损伤大鼠自由基的影响[J],中国针灸,1998,( 7 ) : 409
[26]聂卉等,头穴电鍉针对急性脑血管病的抗脂质过氧化作用[J],针灸临床杂志,1999, ( 12 ): 36
[27]王光义,蒋乃昌,贺志光.头针对脑梗塞患者血浆ET-1,MDA,NO的影响[J].中国针灸,2001,21(4):241
[28]李威,范军铭,贾士奇,等.电针对大鼠全脑缺血.再灌流损伤的保护作用[J].中国针灸,1996,16(11):21
[29]吴绪平,周爽,刘又香.等,头穴透刺对急性脑梗塞大鼠血浆中cAMP, cGMP含量的影响[J].中国针灸,2000; 20 ( 11 ): 694
[30]王亚文,刘又香,靳晶,等.头穴透刺对急性脑梗死大鼠脑组织中cAMP , cGMP含量的影响[J]湖北中医学院学报,2001,3(1):17
[31]许贞峰,吴根诚,曹小定.电针对局灶性脑缺血/再灌注大鼠IL-1RamRNA表达的调节[J].针刺研究,2001,26(3):194
[32]张艳玲、李创鹏、马雅玲.中国针灸,针刺治疗急性脑梗塞对TNF-a, IL-6及肌力的影响[J].2001:21(11):677
[33]雷新强等,头针对急性局灶性脑缺血模型大鼠的影响[J],中国中西医结合杂志,1997, ( 9 ): 544
[34]周炜.工丽平.刘泓等.头针对脑梗塞患者血清肿瘤坏死因子的影响[J].上海针灸杂志2002, 21(1):11
[35]许贞峰,吴根诚,曹小定.电针对局灶性脑缺血/再灌注大鼠IL-1RamRNA表达的调节[J].针刺研究,2001,26(3):194
[36]李菁,肖建华,东贵荣.脑出血急性期头针治疗的临床研究[J].中国中西医结合杂志,1999, 19( 4) : 203 -205
[37]张红星,张唐法.头针治疗中风及对血浆内皮素含量的影响[J ].中国针灸,2002, 22( 12) : 831 -832
[38]王宏宝.精制蝮蛇抗栓酶与头针联用治疗恢复期脑梗死疗效观察[J].华中医学杂志,2002, 26( 3) : 139.
[39]刘宁,马国庆,闰子生.头针丛刺长留针治疗缺血性脑梗塞的临床观察[J].针灸临床杂志.2001.17(3):31.
[40]王光义.蒋乃昌.贺志光.头针对脑梗塞患者血浆ET-1 ,MDA ,NO的影响,[J],中国针灸2001, 21( 4) : 241.
[41]施静,刘晓春,张静,等.电针对脑缺血神经元凋亡影响的形态学研究[J].中国组织化学与细胞化学杂志,1998,7(4):391
[42]王利等,电针对大鼠脑局部缺血再灌流后c-fos , mRNA表达的影响[J],中国针灸,2000(4):241
[43]董劲松,陈伯英.即早表达基c-fos在电针抗局灶性脑缺血损伤中作用的研究[J].针刺研究,2001,26(2):97
[44]马岩璠,王舒,鲁斌,等.醒脑开窍针刺法干预实验性脑梗塞大鼠热休克蛋白基因表达的研究[J].中国针灸,2001,21(2):107
[45] Linda J M,Jean Mary.Apoptosis.Science,1998,281(5381):1301.
[46] Kim GW, Nobuo N, Sugawara TK, et al. Early decrease in DNA repair proteins, Ku70 and Ku86, and subsequent DNA fragmentation after transient focal cerebral ischemia in mice. Stroke,2001,32:1401-1407.
[47]储照虎,吴家幂.大鼠局灶性脑缺血再灌注损伤时神经细胞凋亡及其调控基因的表达.Clin Neurol,2000,13(3):134-136.
[48] Nitatori T. Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis.J Neurosei,1995,15(2):1001.
[49] Sei Y.Internucleosomal DNA fragmentation in gerbil hippocampus following forebrain ischemia.Neurosei Lett,1994,171(1-2):179.
[50] Volpe BT. Temporal pattern of internucleosomal DNA fragmentation in the striatum and hippocampus after transient forebrain ischemia. Neurosei Lett,1995,186(2-3):157.
[51] Greco R, Amantea D, Blandini F, et al. Neuroprotective effect of nitroglycerin in a rodent model of ischemic stroke: evaluation of Bcl-2 expression. Int Rev Neurobiol.2007;82;423-35
[52] Zhao H, Yenari MA, Cheng D, et al. Bcl-2 overexpression protects against neuronloss within the ischemic margin following experimental stroke and inhibits cytochrome c translocation and caspase-3 activity.Neurochem, 2003,85:1026-1036.。
[53] Choi JM, Shin HK, Kim KY, et al. Neuroprotective effect of cilostazol against focal cerebral ischemia via antiapoptotic action in rats. JPharmacol Exp Ther, 2002,300:787-793.
[54] Cao G, MinamiM, PeiW, et a.l Intracellular Bax translocation after transient cerebral ischemia: implications for a role of themitochondrial apoptotic signaling pathway in ischemic neuronal death [J]. Cereb Blood FlowMetab, 2001, 21(4): 321-333. (6): 415-419.
[55] Amemiva S, Kamiva T, Nito C, et al. Anti-apoptotic and neuroprotective effects of edaravone following transient focal ischemia in rats. Eur J pharmacol,2005 Jun 1;516(2):125-30
[56] Zhao H, Yenari MA, Cheng D, et al. Bcl-2 overexpression protects against neuron loss within the ischemic margin following experimental stroke and inhibits cytochrome c translocation and caspase-3 activity. Neurochem ,2003 may;85(4):1026-36
[57] Datta SR, KatsovA, Hu L, et al. 14-3-3 proteins and survival kinases cooperate to inactivate Bad byBH3 domain hosphorylation [J]. MolCel,l 2000, 6(1): 41-45.
[58] CaoYJ, Shibata T, Rainov NG. Liposome-mediated transfer of the Bcl-2 gene results in neuroprotection after in vivo transient focal cerebral ischemia in an animalmodel[J].Gene Ther, 2002, 9
[59] Li DQ, Bai AM, Li Y, et al. Catalpol modulates the expressions of Bcl-2 and Bax and attenuates apoptosis in gerbils after ischemic injury. Brain Res. 2006 oct 18;1115(1):179-81
[60]刘富东,许燕.局灶性脑缺血大鼠神经细胞凋亡及其调控基因bcl-2的表达.皖南医学院学报,2001,20(10):6-7.
[61] Nunez G, Benedict MA, Hu Y, et a.l Caspases: the proteases of the apoptotic pathway[ J]. Oncogene, 1998 , 17 (25): 3237 -3245.
[62] Ashkenazi A, Dixit VM. Death receptors: signaling and modulation[J]. Science, 1998, 281(5381): 1305-1308.
[63] Schulz JB, WellerM, MoskowitzMA. Caspases as treatment targets in stroke and neurodegenerative diseases[ J]. Ann Neurol 1999, 45(4): 421-429.
[64] NiB, Wu X, SuY, eta.l Transientglobal forebrain ischemia induces a prolonged expression of the caspase-3 RNA in rat hippocampal CA1 pyramidal neurons[ J]. Cereb Blood Flow Metab,1998, 18(3): 248-256.
[65] Chen J, Nagayama T, Jin K, et a.l Induction of caspase-3-like proteasemaymediate delayed neuronal death in the hippocampus after transient cerebral ischemia[J]. Neurosc,i 1998 , 18(13):4914-4928.
[66] Ferrer I, Friguls B, Dalfo E,et al. Caspase-dependent and caspase-in-dependentsignalling of apoptosis in the penumbra following middle cerebral artery occlusion in the adult rat. Neuropathol Appl Neurobiol,2003,29:472-481.
[67] Lee SH, Kim M, Kim YJ, et al. Ischemic intensity influences the distribution of delayed infarction and apoptotic cell death following transient focal cerebral ischemia in rats. Brain Res,2002, 956:14-23
[68] Ferrer I, Friquls B, Justici C, et al. Caspase-dependent and caspase-independent signalling of apoptosis in the penumbra following middle cerebral artery occlusion in the adult rat. Neuropathol Appl Neurobiol ,2003 10;(29)5:472-81
[69] Zhu HC, Gao XQ, Xing Y, et al. Inhibition of caspase-3 activation and apoptosis is involved in 3-nitropropionic acid-induced ischemic tolerance to transient focal cerebral ischemia in rats. Mol Neurosic 2004;24(2):299-305
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |