补肾强肝活血法治疗缺血性脑卒中的实验研究
|
摘要
目的：通过建立缺血性中风后动物模型,探讨补肾强肝活血法思想指导下的回春偏瘫方对缺血性中风后神经再生作用的影响,为其修复缺血性脑卒中后的神经功能提供实验依据。
方法：用线栓法造成大脑中动脉阻塞(middle cerebral artery occlusionMCAO)再灌注模型,造模成功后随机分为假手术组,模型组、回春偏瘫方高、中、低剂量(回高组／回中组／回低组)、西药尼莫地平组(西药组),连续给药14天,治疗结束后观察大鼠一般情况和体重改变,按照改良Berdson评分分级法观察神经行为学的改变,TTC染色观察大鼠脑梗死体积变化和脑细胞形态学改变,开颅取脑制成10%脑匀浆溶液,测定脑内SOD、MDA、Glu的水平,用酶联免疫吸附法测定缺血再灌注大鼠颅内NGF水平,免疫组化染色观察脑源性神经营养因子(BDNF),生长相关蛋白-43(GAP-43),突触素p38(SYN)在颅内的表达。
结果：经过MCAO再灌注造模后,大鼠均出现体重下降,神经功能缺失评分明显升高(p<0.01)；实验结束后,与模型组比较,治疗各组体重有所恢复,神经功能缺失情况得到不同程度改善,各治疗组脑梗死体积和脑梗死体积百分比均有不同程度的减少,有极显著的差异(P<0.01)：各治疗组脑组织中Glu水平均有所降低,有明显差异性(P<0.05),中剂量组或高剂量组脑内SOD水平明显升高(P<0.01),MDA水平明显降低(P<0.01),但治疗低剂量组仅对SOD的升高有明显效果(P<0.05),但对MDA的改变效果不明显(P>0.05)；治疗各组脑内NGF水平均高于模型组(P<0.01),尤其是中剂量组效果最佳,疗效与西药组相当(P>0.05)；治疗各组与单纯模型组病理切片结果相比有不同程度改善,其中以中剂量治疗组改善略明显；缺血性卒中大鼠脑内BDNF表达显著增强(P<0.01),其中尤以中剂量组疗效最佳,与西药组无明显差异性(P>0.05)；各剂量组脑内GAP-43表达增强(P<0.01),其中高剂量和中剂量组表达水平与西药组相当,无明显差异性(P>0.05)；但就脑内SYN表达而言,仅中剂量组和高剂量组脑内SYN表达显著增强(P<0.05),与西药组相当(P>0.05)。
结论：回春偏瘫方作为体现补肾强肝活血法的有效方剂,具有促进MCAO再灌注后大鼠神经功能恢复的作用。其作用机理与减小大鼠脑梗死体积,降低脑内Glu、MDA水平,升高脑内SOD、NGF水平,有效改善脑病理形态学,提高颅内BDNF、GAP-43和SYN的表达。
Objective:To investigate the effects of Huichunpiantan Decoction(HD) under guidance of the theory of tonifying liver and kidney and activating blood circulation on treating stroke models of rats after experimental cerebral ischemia (CI).
Methods:The rats after successful modeling the models of middle cerebral artery occlusion (MCAO) were randomized into six groups:sham operation group, model group, high dose group, middle dose group, low dose group and control group. After 14 days treatment course, the changes of weight, behavior, infarct size, the structures of brain tissue, the contents of SOD, MDA, GIu, NGF in brain, and the expressions of BDNF, GAP-43, SYN were investigated.
Results:①HD decreases neural functional deficits in the evaluation of rats and the score with long medication was lower, suggesting that medication can even better improve neural functional deficits;②HD could obviously reduce the infarct size;③HD could increase SOD activity, reducing MDA and Glu content in brain;④HD could markedly increase the content of NGF in brain;⑤HD could protect the structures of brain tissue in experimental cerebral ischemia rats;⑥HD could significantly promote the expression of BDNF in brain;⑦HD could promote the expressions of Gap-43 and SYN.
Conclusions:The experiment shows that HD as an effective decoction by tonifying liver and kidney and activating blood circulation can improve neuronal functional recovery in CI.
方法：用线栓法造成大脑中动脉阻塞(middle cerebral artery occlusionMCAO)再灌注模型,造模成功后随机分为假手术组,模型组、回春偏瘫方高、中、低剂量(回高组／回中组／回低组)、西药尼莫地平组(西药组),连续给药14天,治疗结束后观察大鼠一般情况和体重改变,按照改良Berdson评分分级法观察神经行为学的改变,TTC染色观察大鼠脑梗死体积变化和脑细胞形态学改变,开颅取脑制成10%脑匀浆溶液,测定脑内SOD、MDA、Glu的水平,用酶联免疫吸附法测定缺血再灌注大鼠颅内NGF水平,免疫组化染色观察脑源性神经营养因子(BDNF),生长相关蛋白-43(GAP-43),突触素p38(SYN)在颅内的表达。
结果：经过MCAO再灌注造模后,大鼠均出现体重下降,神经功能缺失评分明显升高(p<0.01)；实验结束后,与模型组比较,治疗各组体重有所恢复,神经功能缺失情况得到不同程度改善,各治疗组脑梗死体积和脑梗死体积百分比均有不同程度的减少,有极显著的差异(P<0.01)：各治疗组脑组织中Glu水平均有所降低,有明显差异性(P<0.05),中剂量组或高剂量组脑内SOD水平明显升高(P<0.01),MDA水平明显降低(P<0.01),但治疗低剂量组仅对SOD的升高有明显效果(P<0.05),但对MDA的改变效果不明显(P>0.05)；治疗各组脑内NGF水平均高于模型组(P<0.01),尤其是中剂量组效果最佳,疗效与西药组相当(P>0.05)；治疗各组与单纯模型组病理切片结果相比有不同程度改善,其中以中剂量治疗组改善略明显；缺血性卒中大鼠脑内BDNF表达显著增强(P<0.01),其中尤以中剂量组疗效最佳,与西药组无明显差异性(P>0.05)；各剂量组脑内GAP-43表达增强(P<0.01),其中高剂量和中剂量组表达水平与西药组相当,无明显差异性(P>0.05)；但就脑内SYN表达而言,仅中剂量组和高剂量组脑内SYN表达显著增强(P<0.05),与西药组相当(P>0.05)。
结论：回春偏瘫方作为体现补肾强肝活血法的有效方剂,具有促进MCAO再灌注后大鼠神经功能恢复的作用。其作用机理与减小大鼠脑梗死体积,降低脑内Glu、MDA水平,升高脑内SOD、NGF水平,有效改善脑病理形态学,提高颅内BDNF、GAP-43和SYN的表达。
Objective:To investigate the effects of Huichunpiantan Decoction(HD) under guidance of the theory of tonifying liver and kidney and activating blood circulation on treating stroke models of rats after experimental cerebral ischemia (CI).
Methods:The rats after successful modeling the models of middle cerebral artery occlusion (MCAO) were randomized into six groups:sham operation group, model group, high dose group, middle dose group, low dose group and control group. After 14 days treatment course, the changes of weight, behavior, infarct size, the structures of brain tissue, the contents of SOD, MDA, GIu, NGF in brain, and the expressions of BDNF, GAP-43, SYN were investigated.
Results:①HD decreases neural functional deficits in the evaluation of rats and the score with long medication was lower, suggesting that medication can even better improve neural functional deficits;②HD could obviously reduce the infarct size;③HD could increase SOD activity, reducing MDA and Glu content in brain;④HD could markedly increase the content of NGF in brain;⑤HD could protect the structures of brain tissue in experimental cerebral ischemia rats;⑥HD could significantly promote the expression of BDNF in brain;⑦HD could promote the expressions of Gap-43 and SYN.
Conclusions:The experiment shows that HD as an effective decoction by tonifying liver and kidney and activating blood circulation can improve neuronal functional recovery in CI.
引文
[1]. Feigin VL. Stroke epidemiology in the developing world. Lancet,2005 Jun 25-Jul 1;365 (9478):2160-2161
[2]He J, Klag MJ, Wu Z, et al. Stroke in the People's Republic of China. II. Meta-analysis of hypertension and risk of stroke. Stroke,1995 Dec;26(12):2228-2232.
[3]Liu M, Wu B, Wang WZ, et al Stroke in China:epidemiology, prevention, and management strategies. Lancet Neurol,2007 May;6(5):456-464.
[4]Yusuf S. Two decades of progress in preventing vascular disease. Lancet,2002 Jul 6:360(9326):2-3.
[5]王小清.中风偏瘫的早期综合治疗.现代中西医结合杂志,2008,17(18)：2805-2806
[6]Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke,1989 Jan;20 (1):84-91
[7]帕尔哈提·热西提,更·党木仁加甫,汪永新,等.改良线栓法制作大鼠局灶性脑缺血模型[J].新疆医科大学学报,2006,29(2)：145-147
[8]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 May-Jun;17(3):472-476
[9]杨文清,施新猷,王四旺,等.光化学法致大鼠脑血栓及水蛭提取物的治疗作用[J].上海实验动物科学,1999,19(4)：197-200.
[10](唐)王冰著,(宋)林亿校正.黄帝内经素问二十四卷[M].人民卫生出版社,1956
[11]李生绍,陈心智点校.黄帝内经灵枢附黄帝八十一难经[M].中医古籍出版社,1997
[12](金)刘完素著,孙桐较注.素问玄机原病式[M].江苏科学技术出版社,1985.46-47
[13](金)李杲撰,傅兴国点校.医学发明活法机要.中医古籍出版社,1987.08.
[14](元)朱震亨著,彭建中点校.丹溪心法,辽宁科学技术出版社,1997：5-8
[15](明)张介宾著.景岳全书[M].中国中医药出版社,1994.
[16](清)叶天士著,(清)华岫云编订.临证指南医案.华夏出版社,1995：1-15
[17](清)王清任.《医林改错》白话解.人民军医出版社,2007.
[18]庞家善.活血化瘀法治疗缺血性中风进展。蛇志,2003,15(1)：49—51
[19]张觉人,杨庆堂.缺血性中风中医药实验研究述要.中西医结合心脑血管病杂志,2005,3(11)：1003—1005
[20]全国中风病急症科研协作组.清开灵注射液治疗急性闭塞性脑血管病147例临床疗效观察[J].北京中医学院学报,1988,11(1)：22—24
[21]邹忆怀.王永炎教授应用化痰通腑法治疗急性期中风病的经验探讨.北京中医药大学学报,1999,22(4)：68—69
[22]林茵绿,杜顺福.急性脑血.管疾病的治疗应注重补肾.[J]中国中医急症,2002,11(1)：34—35
[23]周清安,李建生,王至婉,等.肾虚血瘀在老年缺血性中风发病中的地位及意义[J].中国中医急症,2003,12(1)：67-68.
[24]王至婉,周清安.补肾活血法治疗缺血性中风的研究概况[J].河南中医药学刊,2001,16(3)：15-18
[25]贺景宏,任秀红,杨秀丽.补肾益气活血化瘀法治疗缺血性脑卒中60例疗效观察[J].中西医结合心脑血管病杂志,2003,1(2)：121-122.
[26]冯尊科.半夏天麻白术汤对脑梗塞患者超氧化物歧化酶和丙二醛水平的影响[J].中西医结合实用临床急救,1997,4(6)：275
[27]魏和国,刘欣.平逆通络口服液治疗急性脑梗塞152例临床观察[J].天津中医,1995,12(4)：17-21
[28]周永红.复健片促进缺血性卒中神经发生作用研究[D]博士,山东中医药大学,2005.
[29](宋)陈直著,陈可冀,李春生订正评注.养老奉亲书[M].上海：上海科学技术出版社.1988.5第1版：227
[30](清)周学海撰,王新华点注.读医随笔[M].江苏科学技术出版社,1983：9
[31](宋)严用和撰.济生方[M].人民卫生出版社,1956
[32](汉)张仲景著,(宋)林亿校正杨鹏举,侯仙明,杨延巍注释.金匮要略[M].学苑出版社,2007.
[33](清)吴澄撰,达美君等校注.不居集.中国中医药出版社,2002.
[134]张山雷.中风斠诠.见：陆拯,编.近代中医珍本集.杭州：浙江科学技术出版社.1991
[35]周永红.风药在卒中治疗中的应用[J].吉林中医药,2004,24(8)：2-4
[36](宋)王怀隐撰李佑生整理.太平圣惠方.海南国际新闻出版中心,1995.
[37](清)罗美著 杨德力,鲍玉琴校注.古今名医汇粹[M].中国中医药出版社,1997.
[38](清)罗国纲编.罗氏会约医镜[M].人民卫生出版社,1965.
[39](明)赵献可著,陈永萍校注.医贯[M].学苑出版社,1996.
[40](清)魏之琇编,黄汉儒等点校.续名医类案[M].人民卫生出版社,1997.
[41](清)张隐庵撰述,东山居士校正.侣山堂类辨.千顷堂书局,1935.
[42](战国)秦越人(扁鹊)撰,高丹枫,王琳校注.黄帝八十一难经[M].学苑出版社,2007.
[43](清)张士骧著,上海中医学院中医文献研究所主编.历代中医珍本集成(三七)类中秘旨[M].上海三联书店,1990.
[44][金]刘完素撰.黄帝素问宣明论方[M].上海科学技术出版社,2000.
[45]张学文,李军,韩潮,等.近代中医各家论治中风病荟萃[M].西安：陕西科学技术出版,1997：174-183
[46](清)冯兆张纂辑 田思胜等校注.冯氏锦囊秘录[M].中国中医药出版社,1996.
[47]王洪海,高慧英,安蔚,等.二仙汤加减对急性不完全性脑缺血大鼠脑含水量和SOD活力的影响[J].解剖学研究,2002,24(3)：184-186
[48]杨思军,曹中柱,谷德祥,等.中西医结合治疗急性脑梗塞的疗效和其对促肾上腺激素及超氧化物歧化酶的影响[J].中西医结合实用临床急救,1997,4(3)：104-106.
[49]王洪海,高慧英,崔海庆,等.二仙汤加减对急性不完全性脑缺血大鼠脑保护作用的实验形态学研究[J].解剖学杂志,2001,24(6)：547-551
[50]高慧英,戴兴歧,王洪海,等.加减二仙汤对急性不完全脑缺血大鼠脑水肿的影响[J].中国临床康复,2005,9(33)：107-109
[51](明)戴原礼著,才维秋等校注.秘传证治要诀及类方[M].中国中医药出版社,1998.
[52](汉)许慎,(清)段玉裁注.说文解字注[M].上海古籍出版社,1981.
[53](明)陈嘉谟撰.本草蒙筌[M].人民卫生出版社,1988.
[54](明)缪希雍著,郑金生校注.神农本草经疏[M].中医古籍出版社,2002.
[55](清)黄宫绣著,王淑民校注.本草求真[M].中国中医药出版社,1997.
[56]张锡纯著,王云凯等重校.医学衷中参西录[M].河北科学技术出版社,2002.
[57](清)赵学敏著,闫冰等校注.本草纲目拾遗[M].中国中医药出版社,1998.
[58](清)吴仪洛辑,曲京峰,窦钦鸿点校.本草从新[M].天津科学技术出版社,2003.
[59](明)倪朱谟撰,郑金生,甄雪燕,杨梅香校点.本草汇言[M].中医古籍出版社,2005.
[60](明)贾所学撰.药品化义[M].上海古籍出版社,1996.
[61](唐)甄权撰,尚志钧辑.药性论——药性趋向分类论(合刊本)[M].安徽科学技术出版社,2006.
[62]王一仁主撰.饮片新参[M].上海干顷堂书局,1936.
[163]张成英,姚家庆,田贺村.大鼠脑动脉环的解剖观察[J].解剖学杂志.1996,19(6)：506-508
[64]王继兴.脑梗塞恢复期的中医证候临床研究[D].中国优秀硕士学位论文全文数据库,2008
[65]Bothe HW, Bosma HJ, Hofer H,et al. Selective vulnerability of hippocampus and disturbances of memory storage after mild unilateral ischemia of gerbil brain[J]. Stroke.1986 Nov-Dec;17(6):1160-1163.
[66]Bederson JB, Pitts LH, Germano SM,et al. Evaluation of 2,3,5-triphenyltetra-zolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats[J]. Stroke 1986 Nov-Dec; 17(6):1304-1308.
[67]Schmidley JW. Free radicals in central nervous system ischemia[J]. Stroke.1990 Jul:21 (7):1086-1090.
[68]陈建华,刘晓娟,王启春,等.脑血管病患者血清内源性氧化剂和抗氧化剂水平变化的研究[J].中国危重病急救医学,2003,15(4)：232-234
[69]Olesen SP. Free oxygen radicals decrease electrical resistance of microvascular endothelium in brain[J]. Acta Physiol Scand,1987 Feb;129(2):181-187.
[70]Au AM,.Chan PH, Fishman RA. Stimulation of phospholipase A2 activity by oxygen-derived free radicals in isolated brain capillaries[J]. J Cell Biochem,1985;27 (4): 449-453
[71]Hara H, Sukamoto T. Kogure K. Mechanism and pathogenesis of ischemia-induced neuronal damage[J]. Prog Neurobiol,1993 Jun;40(6):645-670.
[72]江基尧,朱诚.现代颅脑损伤学[M].上海：第二军医大学出版社,1999.133-148
[73]Siesjo BK. Pathophysiology and treatment of focal cerebral ischemia. Part Ⅱ: Mechanisms of damage and treatment[J]. J Neurosurg,1992 Sep;77 (3):337-354.
[74]Cui J, Holmes EH, Greene TG, et al. Oxidative DNA damage precedes DNA fragmenta-tion after experimental stroke in rat brain[J]. FASEB J,2000 May;14(7):955-967.
[75]Love S. Oxidative stress in brain ischemia[J]. Brain Pathol,1999 Jan;9(1):119-131.
[76]Schousboe A. Transport and metabolism of glutamate and GABA in neurons are glial cells[J]. Int Rev Neurobiol.1981;22:1-45.
[77]Tanaka K, Watase K, Manabe T, et al. Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1[J]. Science,1997 Jun 13; 276 (5319): 1699-1702
[78]Butcher SP, Bullock R, Graham DI, et al. Correlation between amino acid release and neuropathologic outcome in rat brain following middle cerebral artery occlusion [J]. Stroke,1990 Dec;21 (12):1727-1.733
[79]Dawson VL, Dawson TM, London ED, et al. Nitric oxide mediates glutamate neuroto-xicity in primary cortical cultures [J]. Proc Natl Acad Sci U S A.1991 Jul 15; 88 (14): 6368-6371
[80]Alessandri B, Bullock R. Glutamate and its receptors in the pathophysiology of brain and spinal cord injuries[J]. Prog Brain Res,1998; 116:303-330
[81]Bender AS, Schousboe A, Reichelt W, et al. Ionic mechanisms in glutamate-induced astrocyte swelling:role of K+ influx[J].J Neurosci Res,1998 May 1;52(3):307-321.
[82]Yuen EC, Mobley WC. Therapeutic potential of neurotrophic factors for neurolo-gical disorders[J].Ann Neurol,1996 Sep;40(3):346-54.
[83]Holtzman DM, Sheldon RA, Jaffe W, et al. Nerve growth factor protects the neonatal brain against hypoxic-ischemic injury [J]. Ann Neurol,1996 Jan;39(1):114-122
[84]Altar CA, Armanini M, Dugich-Djordjevic M,et al. Recovery of cholinergic phenotype in the injured rat neostriatum:roles for endogenous and exogenous nerve growth factor[J].J Neurochem,1992 Dec;59(6):2167-2177
[85]Anderson KJ, Dam D, Lee S, et al. Basic fibroblast growth factor prevents death of lesioned cholinergic neurons in vivo[J]. Nature,1988 Mar 24;332(6162):360-361
[86]Alderson RF, Alterman AL, Barde YA, et al. Brain-derived neurotrophic factor increases survival and differentiated functions of rat septal cholinergic neurons in culture[J]. Neuron,1990 Sep;5(3):297-306.
[87]Chen J, Simon R. Ischemic tolerance in the brain[J]. Neurology,1997 Feb;48(2): 306-311
[88]Arimatsu Y, Miyamoto M. Survival-promoting effect of NGF on in vitro septohippo-campal neurons with cholinergic and GABAergic phenotypes[J]. Brain Res Dev Brain Res, 1991 Feb 22:58(2):189-201.
[89]Schwab JM, Beschorner R, Nguyen TD, et al. Differential cellular accumulation of connective tissue growth factor defines a subset of reactive astrocytes, invading fibroblasts, and endothelial cells following central nervous system injury in rats and humans[J].J Neurotrauma,2001 Apr:18(4):377-388.
[90]Sahin Kaya S, Mahmood A, Li Y, et al. Expression of nestin after traumatic brain injury in rat brain[J]. Brain Res,1999 Sep 4;840(1-2):153-157
[91]Lee TH, Kato H, Chen ST, et al. Expression of nerve growth factor and trkA after transient focal cerebral ischemia in rats[J]. Stroke,1998 Aug; 29 (8):1687-1696
[92]黄坚,邵福源,吴萍嘉,等.急性脑卒中患者血清神经生长因子含量的变化及其临床意义[J].中华老年心脑血管病杂志,2004,6(2)：20.
[93]Ivanova T, Beyer C. Pre-and postnatal expression of brain-derived neurotrophic factor mRNA/protein and tyrosine protein kinase receptor B mRNA in the mouse hippo-campus[J].Neurosci Lett,2001 Jul 6;307(1):21-24
[94]Ohmiya M, Shudai T, Nitta A, et al. Brain-derived neurotrophic factor alters cell migration of particular progenitors in the developing mouse cerebral cortex. [J].Neurosci Lett,2002 Jan 4;317(1):21-24.
[95]Shimazaki T, Arsenijevic Y, Ryan AK, et al. A role for the-POU-III transcription factor Brn-4 in the regulation of striatal neuron precursor differentiation[J]. EMBO J,1999 Jan 15; 18(2):444-456.
[96]Abe K.Therapeutic.potential of neurotrophic factors and neural stem cells against ischemic brain injury [J]. J Cereb Blood Flow Metab,2000 Oct; 20(10):1393-1408.
[97]Walton M, Connor B, Lawlor P, et al. Neuronal death and survival in two models of hypoxic-ischemic brain damage[J]. Brain Res Brain Res Rev,1999 Apr;29(2-3):137-168.
[98]Arai S, Kinouchi H, Akabane A, et al. Induction of brain-derived neurotrophic factor (BDNF) and the receptor trk B mRNA following middle cerebral artery occlusion in rat[J].Neurosci Lett,1996 Jun 14:211(1):57-60.
[99]Wang Y, Sheen VL, Macklis JD. Cortical interneurons upregulate neurotrophins in vivo in response to targeted apoptotic degeneration of neighboring pyramidal neurons[J].Exp Neurol,1998 Dec;154(2):389-402.
[100]Schabitz WR, Schwab S, Spranger M, et al. Intraventricular brain-derived neuro-trophic factor reduces infarct size after focal, cerebral ischemia in rats[J].J Cereb Blood Flow Metab.1997 May; 17(5):500-506.
[101]Schabitz WR, Sommer C, Zoder W, et al. Intravenous brain-derived neurotrophic factor reduces infarct size and counterregulates Bax and Bcl-2 expression after temporary focal cerebral ischemia[J]. Stroke,2000 Sep;31(9):2212-2217
[102]Benowitz LI,Perrone-Bizzozero NI,Neve RL,et al. GAP-43 as a marker for structural plasticity in the mature CNS[J].Prog Brain Res,1990,86:309-320.
[103]Miyake K, Yamamoto W, Tadokoro M, et al. Alterations in hippocampal GAP-43, BDNF, and L1 following sustained cerebral ischemia[J].2002 May 10;935(1-2):24-31.
[104]Carmichael ST. Cellular and molecular mechanisms of neural repair after stroke: making waves[J]. Ann Neurol,2006, May;59(5):735-742.
[105]郑青立,李翔,张美增,等.脑缺血后神经细胞黏附分子和生长相关蛋白-43的表达与神经功能恢复的关系[J].中华物理医学与康复杂志,2005,27(8)：464-467.
[106]王晓英,张均田.突触可塑性与相关蛋白研究进展[J].中国药理学通报,2001,17(4)：369-372.
[107]Li S, Carmichael ST. Growth-associated gene and protein expression in the region of axonal sprouting in the aged brain after stroke[J]. Neurobiol Dis.2006 Aug;23(2):362-373.
[108]Yao GL, Kiyama H, Tohyama M. Distribution of GAP-43 (B50/F1) mRNA in the adult rat brain by in situ hybridization using an alkaline phosphatase labeled probe. [J]. Brain Res Mol Brain Res.1993 Apr;18(1-2):1-16.
[109]Benowitz LI, Routtenberg A.GAP-43:an intrinsic determinant of neuronal development and plasticity[J]. Trends Neurosci,1997 Feb;20(2):84-91.
[110]Benowitz LI, Perrone-Bizzozero NI. The expression of GAP-43 in relation to neuronal growth and plasticity:when, where, how, and why? Porg Brain Res, 1991:89:69-87
[111]张艳萍.神经生长相关蛋白GAP-43与神经再生和发育的关系[J].基础医学与临床,1994：14(1)：23-26.
[112]Skene JH, Jacobson RD, Snipes GJ, et al. A protein induced during nerve growth (GAP-43)is a major component of growth-cone membranes[J]. Science,1986 Aug 15;233 (4765):783-786.
[113]杨辉.GAP-43表达与神经生长可塑性的关系[J].国外医学生理病理科学与临床分册,1995：15(2)：117-118.
[114]S.troemer RP, Kent TA, Hulsebosch CE. Neocortical neural sprouting, synaptoge-nesis, and behavioral recovery after neocortical infarction in rats[J]. Stroke,1995 Nov;26(11):2135-2144
[115]Van Lookeren Campagne M, Oestreicher AB, Van Bergen en Henegouwen PM, et al. Ultrastructural double localization of B-50/GAP43 and synaptophysin (p38) in the neonatal and adult rat hippocampus. [J]. J Neurocytol.1990 Dec; 19(6):948-961.
[116]Thiel G. Synapsin Ⅰ, synapsin Ⅱ, and synaptophysin:marker proteins of synaptic vesicles[J]. Brain Pathol,1993 Jan; 3(1):87-95
[117]Johnston PA, Sudhof TC. The multisubunit structure of synaptophysin. Relation-ship between disulfide bonding and homo-oligomerization[J]. J Biol Chem,1990 May 25;265 (15):8869-8873
[118]Alder J, Lu B, Valtorta F,et al. Calcium-dependent transmitter secretion reconstituted in Xenop'us oocytes:requirement for synaptophysin[J]. Science.1992 Jul 31:257(5070):657-661.
[119]Galli T, McPherson PS, De Camilli P. The VO sector of the V-ATPase, synapto-brevin, and synaptophysin are associated on synaptic vesicles in a Triton X-100-resistant, freeze-thawing sensitive, complex. [J]J Biol Chem,1996 Jan 26;271 (4): 2193-2198.
[120]Valtorta F, Tarelli FT, Campanati L, et al. Synaptophysin and synapsin I as tools for the study of the exo-endocytotic cycle[J]. Cell Biol Int Rep,1989 Dec;13 (12):1023-1038.
[121]Rubenstein JL, Greengard P, Czernik AJ. Calcium-dependent serine phosphory-lation of synaptophysin[J]. Synapse,1993 Feb;13(2):161-172
[122]Chopp M, Li Y, Jiang N. Increase in apoptosis and concomitant reduction of ischemic lesion volume and evidence for synaptogenesis after transient focal cerebral ischemia in rat treated with staurosporine[J]. Brain Res,1999 May 15:828(1-2):197-201
[1](唐)王冰著,(宋)林忆校正.黄帝内经素问二十四卷.人民卫生出版社,1956
[2]李生绍,陈心智点校.黄帝内经灵枢附黄帝八十一难经.中医古籍出版社,1997
[3](汉)张仲景著,(宋)林亿校正,杨鹏举,侯仙明,杨延巍注释.金匮要略.学苑出版社,2007.
[4](隋)巢元方撰,黄作阵点校.诸病源候论.辽宁科学技术出版社,1997.
[5](唐)孙思邈撰,鲁兆麟主校.备急千金要方.辽宁科学技术出版社,1997.
[6](宋)陈言著.三因极—病证方论18卷.人民卫生出版社,1957.
[7](宋)严用和撰.济生方.人民卫生出版社,1956
[8](宋)陈自明原著,田代华等点校.妇人大全良方.天津科学技术出版社,2003.
[9](金)刘完素著,孙桐较注.素问玄机原病式.江苏科学技术出版社,1985：46-47
[10]刘完素述.素问病机气宜保命集.中华书局,1985：31-32
[11](金)刘完素撰.黄帝素问宣明论方.上海科学技术出版社,2000.
[12](金)张从正撰,张海岑等校注.《儒门事亲》校注.河南科学技术出版社,1984：219,18,19,229
[13](金)李果撰,傅兴国点校.医学发明活法机要.中医古籍出版社,1987：37
[14](元)朱震亨著,彭建中点校.丹溪心法.辽宁科学技术出版社,1997：5-8
[15](明)张介宾著.景岳全书[M].中国中医药出版社,1994.
[16](明)杨继洲著.针灸大成10卷.人民卫生出版社,1963：341-342,333,
[17](明)赵献可著,陈永萍校注.医贯.学苑出版社,1996：29-32
[18]缪希雍,王新华撰.先醒斋医学广笔记.江苏科学技术出版社,1983.1-2
[19]任春荣.缪希雍医学全书[M].北京：中国中医药出版社,1999：50
[20](清)尤怡著,张印生等校注.金匮翼.中医古籍出版社,2003：1-8
[21](清)叶天士著,(清)华岫云编订.临证指南医案.华夏出版社,1995：1-15
[22](清)王清任著；陕西省中医研究院注释.医林改错注释.人民卫生出版社,1985：106,120,
[23](清)张士骧著,上海中医学院中医文献研究所主编.历代中医珍本集成三七类中秘旨.上海三联书店,1990：394-395
[24]张山雷.中风斠诠.见：陆拯,编.近代中医珍本集.杭州：浙江科学技术出版社.1991：377,364,358-359
[25]张锡纯.医学衷中参西录.石家庄：河北人民出版社,1977：520
[2]He J, Klag MJ, Wu Z, et al. Stroke in the People's Republic of China. II. Meta-analysis of hypertension and risk of stroke. Stroke,1995 Dec;26(12):2228-2232.
[3]Liu M, Wu B, Wang WZ, et al Stroke in China:epidemiology, prevention, and management strategies. Lancet Neurol,2007 May;6(5):456-464.
[4]Yusuf S. Two decades of progress in preventing vascular disease. Lancet,2002 Jul 6:360(9326):2-3.
[5]王小清.中风偏瘫的早期综合治疗.现代中西医结合杂志,2008,17(18)：2805-2806
[6]Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke,1989 Jan;20 (1):84-91
[7]帕尔哈提·热西提,更·党木仁加甫,汪永新,等.改良线栓法制作大鼠局灶性脑缺血模型[J].新疆医科大学学报,2006,29(2)：145-147
[8]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 May-Jun;17(3):472-476
[9]杨文清,施新猷,王四旺,等.光化学法致大鼠脑血栓及水蛭提取物的治疗作用[J].上海实验动物科学,1999,19(4)：197-200.
[10](唐)王冰著,(宋)林亿校正.黄帝内经素问二十四卷[M].人民卫生出版社,1956
[11]李生绍,陈心智点校.黄帝内经灵枢附黄帝八十一难经[M].中医古籍出版社,1997
[12](金)刘完素著,孙桐较注.素问玄机原病式[M].江苏科学技术出版社,1985.46-47
[13](金)李杲撰,傅兴国点校.医学发明活法机要.中医古籍出版社,1987.08.
[14](元)朱震亨著,彭建中点校.丹溪心法,辽宁科学技术出版社,1997：5-8
[15](明)张介宾著.景岳全书[M].中国中医药出版社,1994.
[16](清)叶天士著,(清)华岫云编订.临证指南医案.华夏出版社,1995：1-15
[17](清)王清任.《医林改错》白话解.人民军医出版社,2007.
[18]庞家善.活血化瘀法治疗缺血性中风进展。蛇志,2003,15(1)：49—51
[19]张觉人,杨庆堂.缺血性中风中医药实验研究述要.中西医结合心脑血管病杂志,2005,3(11)：1003—1005
[20]全国中风病急症科研协作组.清开灵注射液治疗急性闭塞性脑血管病147例临床疗效观察[J].北京中医学院学报,1988,11(1)：22—24
[21]邹忆怀.王永炎教授应用化痰通腑法治疗急性期中风病的经验探讨.北京中医药大学学报,1999,22(4)：68—69
[22]林茵绿,杜顺福.急性脑血.管疾病的治疗应注重补肾.[J]中国中医急症,2002,11(1)：34—35
[23]周清安,李建生,王至婉,等.肾虚血瘀在老年缺血性中风发病中的地位及意义[J].中国中医急症,2003,12(1)：67-68.
[24]王至婉,周清安.补肾活血法治疗缺血性中风的研究概况[J].河南中医药学刊,2001,16(3)：15-18
[25]贺景宏,任秀红,杨秀丽.补肾益气活血化瘀法治疗缺血性脑卒中60例疗效观察[J].中西医结合心脑血管病杂志,2003,1(2)：121-122.
[26]冯尊科.半夏天麻白术汤对脑梗塞患者超氧化物歧化酶和丙二醛水平的影响[J].中西医结合实用临床急救,1997,4(6)：275
[27]魏和国,刘欣.平逆通络口服液治疗急性脑梗塞152例临床观察[J].天津中医,1995,12(4)：17-21
[28]周永红.复健片促进缺血性卒中神经发生作用研究[D]博士,山东中医药大学,2005.
[29](宋)陈直著,陈可冀,李春生订正评注.养老奉亲书[M].上海：上海科学技术出版社.1988.5第1版：227
[30](清)周学海撰,王新华点注.读医随笔[M].江苏科学技术出版社,1983：9
[31](宋)严用和撰.济生方[M].人民卫生出版社,1956
[32](汉)张仲景著,(宋)林亿校正杨鹏举,侯仙明,杨延巍注释.金匮要略[M].学苑出版社,2007.
[33](清)吴澄撰,达美君等校注.不居集.中国中医药出版社,2002.
[134]张山雷.中风斠诠.见：陆拯,编.近代中医珍本集.杭州：浙江科学技术出版社.1991
[35]周永红.风药在卒中治疗中的应用[J].吉林中医药,2004,24(8)：2-4
[36](宋)王怀隐撰李佑生整理.太平圣惠方.海南国际新闻出版中心,1995.
[37](清)罗美著 杨德力,鲍玉琴校注.古今名医汇粹[M].中国中医药出版社,1997.
[38](清)罗国纲编.罗氏会约医镜[M].人民卫生出版社,1965.
[39](明)赵献可著,陈永萍校注.医贯[M].学苑出版社,1996.
[40](清)魏之琇编,黄汉儒等点校.续名医类案[M].人民卫生出版社,1997.
[41](清)张隐庵撰述,东山居士校正.侣山堂类辨.千顷堂书局,1935.
[42](战国)秦越人(扁鹊)撰,高丹枫,王琳校注.黄帝八十一难经[M].学苑出版社,2007.
[43](清)张士骧著,上海中医学院中医文献研究所主编.历代中医珍本集成(三七)类中秘旨[M].上海三联书店,1990.
[44][金]刘完素撰.黄帝素问宣明论方[M].上海科学技术出版社,2000.
[45]张学文,李军,韩潮,等.近代中医各家论治中风病荟萃[M].西安：陕西科学技术出版,1997：174-183
[46](清)冯兆张纂辑 田思胜等校注.冯氏锦囊秘录[M].中国中医药出版社,1996.
[47]王洪海,高慧英,安蔚,等.二仙汤加减对急性不完全性脑缺血大鼠脑含水量和SOD活力的影响[J].解剖学研究,2002,24(3)：184-186
[48]杨思军,曹中柱,谷德祥,等.中西医结合治疗急性脑梗塞的疗效和其对促肾上腺激素及超氧化物歧化酶的影响[J].中西医结合实用临床急救,1997,4(3)：104-106.
[49]王洪海,高慧英,崔海庆,等.二仙汤加减对急性不完全性脑缺血大鼠脑保护作用的实验形态学研究[J].解剖学杂志,2001,24(6)：547-551
[50]高慧英,戴兴歧,王洪海,等.加减二仙汤对急性不完全脑缺血大鼠脑水肿的影响[J].中国临床康复,2005,9(33)：107-109
[51](明)戴原礼著,才维秋等校注.秘传证治要诀及类方[M].中国中医药出版社,1998.
[52](汉)许慎,(清)段玉裁注.说文解字注[M].上海古籍出版社,1981.
[53](明)陈嘉谟撰.本草蒙筌[M].人民卫生出版社,1988.
[54](明)缪希雍著,郑金生校注.神农本草经疏[M].中医古籍出版社,2002.
[55](清)黄宫绣著,王淑民校注.本草求真[M].中国中医药出版社,1997.
[56]张锡纯著,王云凯等重校.医学衷中参西录[M].河北科学技术出版社,2002.
[57](清)赵学敏著,闫冰等校注.本草纲目拾遗[M].中国中医药出版社,1998.
[58](清)吴仪洛辑,曲京峰,窦钦鸿点校.本草从新[M].天津科学技术出版社,2003.
[59](明)倪朱谟撰,郑金生,甄雪燕,杨梅香校点.本草汇言[M].中医古籍出版社,2005.
[60](明)贾所学撰.药品化义[M].上海古籍出版社,1996.
[61](唐)甄权撰,尚志钧辑.药性论——药性趋向分类论(合刊本)[M].安徽科学技术出版社,2006.
[62]王一仁主撰.饮片新参[M].上海干顷堂书局,1936.
[163]张成英,姚家庆,田贺村.大鼠脑动脉环的解剖观察[J].解剖学杂志.1996,19(6)：506-508
[64]王继兴.脑梗塞恢复期的中医证候临床研究[D].中国优秀硕士学位论文全文数据库,2008
[65]Bothe HW, Bosma HJ, Hofer H,et al. Selective vulnerability of hippocampus and disturbances of memory storage after mild unilateral ischemia of gerbil brain[J]. Stroke.1986 Nov-Dec;17(6):1160-1163.
[66]Bederson JB, Pitts LH, Germano SM,et al. Evaluation of 2,3,5-triphenyltetra-zolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats[J]. Stroke 1986 Nov-Dec; 17(6):1304-1308.
[67]Schmidley JW. Free radicals in central nervous system ischemia[J]. Stroke.1990 Jul:21 (7):1086-1090.
[68]陈建华,刘晓娟,王启春,等.脑血管病患者血清内源性氧化剂和抗氧化剂水平变化的研究[J].中国危重病急救医学,2003,15(4)：232-234
[69]Olesen SP. Free oxygen radicals decrease electrical resistance of microvascular endothelium in brain[J]. Acta Physiol Scand,1987 Feb;129(2):181-187.
[70]Au AM,.Chan PH, Fishman RA. Stimulation of phospholipase A2 activity by oxygen-derived free radicals in isolated brain capillaries[J]. J Cell Biochem,1985;27 (4): 449-453
[71]Hara H, Sukamoto T. Kogure K. Mechanism and pathogenesis of ischemia-induced neuronal damage[J]. Prog Neurobiol,1993 Jun;40(6):645-670.
[72]江基尧,朱诚.现代颅脑损伤学[M].上海：第二军医大学出版社,1999.133-148
[73]Siesjo BK. Pathophysiology and treatment of focal cerebral ischemia. Part Ⅱ: Mechanisms of damage and treatment[J]. J Neurosurg,1992 Sep;77 (3):337-354.
[74]Cui J, Holmes EH, Greene TG, et al. Oxidative DNA damage precedes DNA fragmenta-tion after experimental stroke in rat brain[J]. FASEB J,2000 May;14(7):955-967.
[75]Love S. Oxidative stress in brain ischemia[J]. Brain Pathol,1999 Jan;9(1):119-131.
[76]Schousboe A. Transport and metabolism of glutamate and GABA in neurons are glial cells[J]. Int Rev Neurobiol.1981;22:1-45.
[77]Tanaka K, Watase K, Manabe T, et al. Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1[J]. Science,1997 Jun 13; 276 (5319): 1699-1702
[78]Butcher SP, Bullock R, Graham DI, et al. Correlation between amino acid release and neuropathologic outcome in rat brain following middle cerebral artery occlusion [J]. Stroke,1990 Dec;21 (12):1727-1.733
[79]Dawson VL, Dawson TM, London ED, et al. Nitric oxide mediates glutamate neuroto-xicity in primary cortical cultures [J]. Proc Natl Acad Sci U S A.1991 Jul 15; 88 (14): 6368-6371
[80]Alessandri B, Bullock R. Glutamate and its receptors in the pathophysiology of brain and spinal cord injuries[J]. Prog Brain Res,1998; 116:303-330
[81]Bender AS, Schousboe A, Reichelt W, et al. Ionic mechanisms in glutamate-induced astrocyte swelling:role of K+ influx[J].J Neurosci Res,1998 May 1;52(3):307-321.
[82]Yuen EC, Mobley WC. Therapeutic potential of neurotrophic factors for neurolo-gical disorders[J].Ann Neurol,1996 Sep;40(3):346-54.
[83]Holtzman DM, Sheldon RA, Jaffe W, et al. Nerve growth factor protects the neonatal brain against hypoxic-ischemic injury [J]. Ann Neurol,1996 Jan;39(1):114-122
[84]Altar CA, Armanini M, Dugich-Djordjevic M,et al. Recovery of cholinergic phenotype in the injured rat neostriatum:roles for endogenous and exogenous nerve growth factor[J].J Neurochem,1992 Dec;59(6):2167-2177
[85]Anderson KJ, Dam D, Lee S, et al. Basic fibroblast growth factor prevents death of lesioned cholinergic neurons in vivo[J]. Nature,1988 Mar 24;332(6162):360-361
[86]Alderson RF, Alterman AL, Barde YA, et al. Brain-derived neurotrophic factor increases survival and differentiated functions of rat septal cholinergic neurons in culture[J]. Neuron,1990 Sep;5(3):297-306.
[87]Chen J, Simon R. Ischemic tolerance in the brain[J]. Neurology,1997 Feb;48(2): 306-311
[88]Arimatsu Y, Miyamoto M. Survival-promoting effect of NGF on in vitro septohippo-campal neurons with cholinergic and GABAergic phenotypes[J]. Brain Res Dev Brain Res, 1991 Feb 22:58(2):189-201.
[89]Schwab JM, Beschorner R, Nguyen TD, et al. Differential cellular accumulation of connective tissue growth factor defines a subset of reactive astrocytes, invading fibroblasts, and endothelial cells following central nervous system injury in rats and humans[J].J Neurotrauma,2001 Apr:18(4):377-388.
[90]Sahin Kaya S, Mahmood A, Li Y, et al. Expression of nestin after traumatic brain injury in rat brain[J]. Brain Res,1999 Sep 4;840(1-2):153-157
[91]Lee TH, Kato H, Chen ST, et al. Expression of nerve growth factor and trkA after transient focal cerebral ischemia in rats[J]. Stroke,1998 Aug; 29 (8):1687-1696
[92]黄坚,邵福源,吴萍嘉,等.急性脑卒中患者血清神经生长因子含量的变化及其临床意义[J].中华老年心脑血管病杂志,2004,6(2)：20.
[93]Ivanova T, Beyer C. Pre-and postnatal expression of brain-derived neurotrophic factor mRNA/protein and tyrosine protein kinase receptor B mRNA in the mouse hippo-campus[J].Neurosci Lett,2001 Jul 6;307(1):21-24
[94]Ohmiya M, Shudai T, Nitta A, et al. Brain-derived neurotrophic factor alters cell migration of particular progenitors in the developing mouse cerebral cortex. [J].Neurosci Lett,2002 Jan 4;317(1):21-24.
[95]Shimazaki T, Arsenijevic Y, Ryan AK, et al. A role for the-POU-III transcription factor Brn-4 in the regulation of striatal neuron precursor differentiation[J]. EMBO J,1999 Jan 15; 18(2):444-456.
[96]Abe K.Therapeutic.potential of neurotrophic factors and neural stem cells against ischemic brain injury [J]. J Cereb Blood Flow Metab,2000 Oct; 20(10):1393-1408.
[97]Walton M, Connor B, Lawlor P, et al. Neuronal death and survival in two models of hypoxic-ischemic brain damage[J]. Brain Res Brain Res Rev,1999 Apr;29(2-3):137-168.
[98]Arai S, Kinouchi H, Akabane A, et al. Induction of brain-derived neurotrophic factor (BDNF) and the receptor trk B mRNA following middle cerebral artery occlusion in rat[J].Neurosci Lett,1996 Jun 14:211(1):57-60.
[99]Wang Y, Sheen VL, Macklis JD. Cortical interneurons upregulate neurotrophins in vivo in response to targeted apoptotic degeneration of neighboring pyramidal neurons[J].Exp Neurol,1998 Dec;154(2):389-402.
[100]Schabitz WR, Schwab S, Spranger M, et al. Intraventricular brain-derived neuro-trophic factor reduces infarct size after focal, cerebral ischemia in rats[J].J Cereb Blood Flow Metab.1997 May; 17(5):500-506.
[101]Schabitz WR, Sommer C, Zoder W, et al. Intravenous brain-derived neurotrophic factor reduces infarct size and counterregulates Bax and Bcl-2 expression after temporary focal cerebral ischemia[J]. Stroke,2000 Sep;31(9):2212-2217
[102]Benowitz LI,Perrone-Bizzozero NI,Neve RL,et al. GAP-43 as a marker for structural plasticity in the mature CNS[J].Prog Brain Res,1990,86:309-320.
[103]Miyake K, Yamamoto W, Tadokoro M, et al. Alterations in hippocampal GAP-43, BDNF, and L1 following sustained cerebral ischemia[J].2002 May 10;935(1-2):24-31.
[104]Carmichael ST. Cellular and molecular mechanisms of neural repair after stroke: making waves[J]. Ann Neurol,2006, May;59(5):735-742.
[105]郑青立,李翔,张美增,等.脑缺血后神经细胞黏附分子和生长相关蛋白-43的表达与神经功能恢复的关系[J].中华物理医学与康复杂志,2005,27(8)：464-467.
[106]王晓英,张均田.突触可塑性与相关蛋白研究进展[J].中国药理学通报,2001,17(4)：369-372.
[107]Li S, Carmichael ST. Growth-associated gene and protein expression in the region of axonal sprouting in the aged brain after stroke[J]. Neurobiol Dis.2006 Aug;23(2):362-373.
[108]Yao GL, Kiyama H, Tohyama M. Distribution of GAP-43 (B50/F1) mRNA in the adult rat brain by in situ hybridization using an alkaline phosphatase labeled probe. [J]. Brain Res Mol Brain Res.1993 Apr;18(1-2):1-16.
[109]Benowitz LI, Routtenberg A.GAP-43:an intrinsic determinant of neuronal development and plasticity[J]. Trends Neurosci,1997 Feb;20(2):84-91.
[110]Benowitz LI, Perrone-Bizzozero NI. The expression of GAP-43 in relation to neuronal growth and plasticity:when, where, how, and why? Porg Brain Res, 1991:89:69-87
[111]张艳萍.神经生长相关蛋白GAP-43与神经再生和发育的关系[J].基础医学与临床,1994：14(1)：23-26.
[112]Skene JH, Jacobson RD, Snipes GJ, et al. A protein induced during nerve growth (GAP-43)is a major component of growth-cone membranes[J]. Science,1986 Aug 15;233 (4765):783-786.
[113]杨辉.GAP-43表达与神经生长可塑性的关系[J].国外医学生理病理科学与临床分册,1995：15(2)：117-118.
[114]S.troemer RP, Kent TA, Hulsebosch CE. Neocortical neural sprouting, synaptoge-nesis, and behavioral recovery after neocortical infarction in rats[J]. Stroke,1995 Nov;26(11):2135-2144
[115]Van Lookeren Campagne M, Oestreicher AB, Van Bergen en Henegouwen PM, et al. Ultrastructural double localization of B-50/GAP43 and synaptophysin (p38) in the neonatal and adult rat hippocampus. [J]. J Neurocytol.1990 Dec; 19(6):948-961.
[116]Thiel G. Synapsin Ⅰ, synapsin Ⅱ, and synaptophysin:marker proteins of synaptic vesicles[J]. Brain Pathol,1993 Jan; 3(1):87-95
[117]Johnston PA, Sudhof TC. The multisubunit structure of synaptophysin. Relation-ship between disulfide bonding and homo-oligomerization[J]. J Biol Chem,1990 May 25;265 (15):8869-8873
[118]Alder J, Lu B, Valtorta F,et al. Calcium-dependent transmitter secretion reconstituted in Xenop'us oocytes:requirement for synaptophysin[J]. Science.1992 Jul 31:257(5070):657-661.
[119]Galli T, McPherson PS, De Camilli P. The VO sector of the V-ATPase, synapto-brevin, and synaptophysin are associated on synaptic vesicles in a Triton X-100-resistant, freeze-thawing sensitive, complex. [J]J Biol Chem,1996 Jan 26;271 (4): 2193-2198.
[120]Valtorta F, Tarelli FT, Campanati L, et al. Synaptophysin and synapsin I as tools for the study of the exo-endocytotic cycle[J]. Cell Biol Int Rep,1989 Dec;13 (12):1023-1038.
[121]Rubenstein JL, Greengard P, Czernik AJ. Calcium-dependent serine phosphory-lation of synaptophysin[J]. Synapse,1993 Feb;13(2):161-172
[122]Chopp M, Li Y, Jiang N. Increase in apoptosis and concomitant reduction of ischemic lesion volume and evidence for synaptogenesis after transient focal cerebral ischemia in rat treated with staurosporine[J]. Brain Res,1999 May 15:828(1-2):197-201
[1](唐)王冰著,(宋)林忆校正.黄帝内经素问二十四卷.人民卫生出版社,1956
[2]李生绍,陈心智点校.黄帝内经灵枢附黄帝八十一难经.中医古籍出版社,1997
[3](汉)张仲景著,(宋)林亿校正,杨鹏举,侯仙明,杨延巍注释.金匮要略.学苑出版社,2007.
[4](隋)巢元方撰,黄作阵点校.诸病源候论.辽宁科学技术出版社,1997.
[5](唐)孙思邈撰,鲁兆麟主校.备急千金要方.辽宁科学技术出版社,1997.
[6](宋)陈言著.三因极—病证方论18卷.人民卫生出版社,1957.
[7](宋)严用和撰.济生方.人民卫生出版社,1956
[8](宋)陈自明原著,田代华等点校.妇人大全良方.天津科学技术出版社,2003.
[9](金)刘完素著,孙桐较注.素问玄机原病式.江苏科学技术出版社,1985：46-47
[10]刘完素述.素问病机气宜保命集.中华书局,1985：31-32
[11](金)刘完素撰.黄帝素问宣明论方.上海科学技术出版社,2000.
[12](金)张从正撰,张海岑等校注.《儒门事亲》校注.河南科学技术出版社,1984：219,18,19,229
[13](金)李果撰,傅兴国点校.医学发明活法机要.中医古籍出版社,1987：37
[14](元)朱震亨著,彭建中点校.丹溪心法.辽宁科学技术出版社,1997：5-8
[15](明)张介宾著.景岳全书[M].中国中医药出版社,1994.
[16](明)杨继洲著.针灸大成10卷.人民卫生出版社,1963：341-342,333,
[17](明)赵献可著,陈永萍校注.医贯.学苑出版社,1996：29-32
[18]缪希雍,王新华撰.先醒斋医学广笔记.江苏科学技术出版社,1983.1-2
[19]任春荣.缪希雍医学全书[M].北京：中国中医药出版社,1999：50
[20](清)尤怡著,张印生等校注.金匮翼.中医古籍出版社,2003：1-8
[21](清)叶天士著,(清)华岫云编订.临证指南医案.华夏出版社,1995：1-15
[22](清)王清任著；陕西省中医研究院注释.医林改错注释.人民卫生出版社,1985：106,120,
[23](清)张士骧著,上海中医学院中医文献研究所主编.历代中医珍本集成三七类中秘旨.上海三联书店,1990：394-395
[24]张山雷.中风斠诠.见：陆拯,编.近代中医珍本集.杭州：浙江科学技术出版社.1991：377,364,358-359
[25]张锡纯.医学衷中参西录.石家庄：河北人民出版社,1977：520