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滋补肝肾以调控NEI促进神经功能重塑的路径研究
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摘要
目的:探讨滋补肝肾中药复健片促进缺血性卒中后神经功能重塑的路径。方法:基于“滋补肝肾以生髓”的中医理论,以MCAO大鼠为实验对象,通过观察复健片调控神经-内分泌-免疫网络(NEI)自稳态和拮抗胶质瘢痕增生的效应,初步探索滋补肝肾中药促进神经功能重塑的路径。分三部分:(一)利用酶联免疫吸附法、荧光分光度法、放射免疫法、免疫组织化学法检测瘦素(Leptin)、5-HT、血管活性肠肽(VIP)、CD8+T细胞、促肾上腺皮质激素(ACTH)、睾丸酮(T)的变化,研究复健片通过调控NEI以抑制缺血性卒中后过度免疫反应的效应;(二)利用酶联免疫吸附法与免疫组织化学法检测基质金属蛋白酶(MMPS),波形蛋白(Vim)与胶质纤维酸性蛋白(GFAP)的变化,研究免疫反应受抑制后胶质瘢痕增生减弱的效应;(三)根据以往工作基础和本课题的结果从理论上探讨滋补肝肾中药减弱胶质瘢痕增生对神经功能重塑的促进效应。结果:复健片可使血清中Leptin的表达下调;缺血脑皮质中5-HT、VIP及CD8+T细胞表达上调;血浆ACTH及血清T上调;缺血脑皮质中MMP-2、MMP-9活性增强;脑梗死后期Vim及GFAP的表达降低。结论:滋补肝肾中药可通过调控NEI自稳态以拮抗胶质瘢痕增生,进而促进缺血性卒中后神经功能重塑。
Objective: To investigate the effects of one particular therapeutic method of Traditional Chinese Medicine (TCM) namely“the nourishing of liver and kidney”on the promotion of neurogenesis through the regulating of NEI after cerebral ischemic stroke. Methods: Based on the TCM theory that“nourishing liver and kidney can produce marrow”, we set up a MCAO rat model and then utilized a TCM herbal medication called Fujian tablet (which is specifically formulated to“nourish liver and kidney”). We observed its’effects on regulating NEI and inhibiting the hyperplasia of glial scar as one pathway for the promotion of neurogenesis. The research includes 3 parts: Part one, six indexes including Leptin, 5-HT, VIP, CD8+T, ACTH, Testosterone were measured in an enzyme linked immunosorbent assay with radio-immunity and immunohistochemical methods used to evaluate the effects of Fujian tablet on inhibiting excessive immunological reactions after cerebral ischemic stroke by the regulation of NEI. Part 2, four indexes including MMP-2, MMP-9, Vim and GFAP were measured with enzyme linked immunosorbent assay and immunohistochemical methods to evaluate the effects of Fujian tablet on inhibiting the hyperplasia of glial scaring. Part 3, based on the results observed in parts one and two, to evaluate the overall capacity for Chinese herbs to promote neurogenesis. Results: Fujian tablet can decrease the expression of Leptin in blood serum, increase the expression of 5-HT, VIP, CD8+T, MMP-2 and MMP-9 in brain tissue, increase the expression of ACTH and TESTO in blood plasma, and decrease the expression of Vim and GFAP in brain tissue. Conclusions: Traditional Chinese Medicine for the nourishing of liver and kidney can significantly improve the symptoms of functional deficit after cerebral ischemic stroke with one of the important mechanisms being the promotion of neurogenesis. Nourishing the liver and kidney is of great importance in regulating the homeostasis of NEI in order to inhibit the hyperplasia of glial scar, and this is closely related to the promotion of neurogenesis.
引文
[1]李忠.缺血性脑血管疾病,北京:北京科学技术出版社,2002,2210.
    [2]张国瑾,赵增荣.国外脑血管病研究进展,北京:中国医药科技出版社,2000,21-510.
    [3]秦震.急性缺血性脑血管病临床治疗研究近况.中华神经科杂志,1998;31(6):367-369.
    [4]徐如祥.中枢神经系统损伤后神经再生的策略.中华神经医学杂志,2007;6(2):109.
    [5]程飚,付小兵,盛志勇.免疫因素在瘢痕形成和发展中的作用.中国临床康复,2002;6(4):473.
    [6] Smith C, Berry M, Clarke WE, et al.Differential expression of fibroblast growth factor-2 and fibroblast growth factor receptor-1 in a scarring and nonscarring model of CNS injury in the rat.Eur J Neurosci, 2003;13(3): 443-456.
    [7]弗里乔夫·卡普拉.转折点,成都:四川科学技术出版社,1988:41.
    [8]王阶,王永炎.复杂系统理论与中医方证研究.中国中医药信息杂志,2001;8(9):27.
    [9]王永炎.中医药研究中系统论与还原论的关联关系.世界科学技术——中医药现代化,2007;9(1):70-71.
    [10]李梢,王永炎,季梁,等.复杂系统意义下的中医药学及其案例研究.系统仿真学报,2002;14(11):1429-1431,1442.
    [11]白云静,申洪波,王永炎,等.基于复杂性科学的中医学发展取向与方略.中国中医药信息杂志,2005;12(1):2-4.
    [12]陈建南,赖小平,周华.试从非线性视角看中医方剂实质.世界科学技术——中药现代化*中医现代化,2001;3(3):37.
    [13]谢启文.现代神经内分泌学,上海:上海医科大学出版社,1999,351-362.
    [14]张万全,王复周.神经,免疫及内分泌系统间的关系.生理科学进展,1993;24(3):208.
    [15]陈爱娟,卓安山,杨秋佳,等.脑缺血再灌注对大鼠下丘脑-垂体-肾上腺-胸腺轴的影响.上海免疫学杂志,2002;22(4):272.
    [16]陈曼娥,王景周,琚亚非,等.下丘脑-垂体-肾上腺轴应变调控与脑缺血再灌流相关性的研究.中国危重病急救医学,1996;8(3):131.
    [17]武继涛.复方仙灵脾注射液对全脑缺血再灌注大鼠脑组织含水量、血清TNF-α、IL-1、IL-6含量的影响.中医药学刊,2003;21(11):1905.
    [18]蔡定芳,沈自尹.中西医结合神经内分泌免疫网络研究的思考.中国中西医结合杂志,1997;17(7):442.
    [19]季钟朴.现代中医生理学基础,北京:学苑出版社,1991,233.
    [20]李瀚.“肝肾同源”的理论探讨.中国中医基础医学杂志,2000;6(7):6.
    [21]任小巧,卢跃卿,郭秀珍,等.肝肾阴虚证与神经内分泌网络关系探讨.河南中医,1998;18(6):338-339.
    [22]王新陆.脑血辨证,北京:中国医药科技出版社,2002,1-154.
    [23] Yamashita K, Ouchi K, Shirai M, et al.Distribution of Chamydia pneumonias infection in the antherosclerotic carotid artery.Stroke, 1998; 29(4):773-778.
    [24] Epstein SE.The multiple mechanisms by which infection may contribute to antherosclerosis development and course.Circulation Research, 2002; 90(1):2-4.
    [25] Kiechl S, Werner P, Egger G, et al.Active and passive smoking, chrotic infections, and the risk of carotid atherosclerosis: Prospective results from the bruneck study. Stroke, 2002; 33(9):2170-2176.
    [26]周永红.风药在卒中治疗中的应用.吉林中医药,2004;24(8):2-4.
    [27]周永红.中风后遗症证治概况.山东中医杂志,2001;20(l):58-61.
    [28]张学文,李军,韩潮,等.近代中医各家论治中风病荟萃,西安:陕西科学技术出版社,1997,174-183.
    [29]陈召.论养阴法是治疗中风的重要法则.中医药研究,1998;14(6):28-31.
    [30]何立军,周启新,钱元恕,等.首乌、决明子、大黄、虎杖、山楂抗动脉粥样硬化作用的实验研究.中药药理与临床,1987;4(4):41.
    [31]陈计,夏炎兴,杨秋美,等.何首乌吸收成分对大鼠2倍体细胞生长和传代的影响.上海中医药杂志,1995;(8):43.
    [32]王巍.首乌对老年鹌鹑寿命和脂质代谢的影响.中西医结合杂志,1998;8(4):223.
    [33]蔡永敏,任玉让,王黎,等.最新中药药理与临床应用,北京:华夏出版社,1999,406-477.
    [34]黄泰康.现代本草纲目,北京:中国医药科技出版社,2001,998-2136.
    [35]王文静,薛咏梅,赵荣华,等.何首乌的化学成分和药理作用研究进展.云南中医学院学报,2007;30(3):63.
    [36]廖海民,胡正海.何首乌的生物学及化学成分研究进展.中草药,2005;36(2):312.
    [37]华一俐,吴慧平,张融瑞,等.桑寄生的降脂作用和抗脂质过氧化反应的研究.中国医药学报,1995;10(l):40.
    [38]张秀敏,刘冉,许津.中药桑寄生的抗Ⅰ型变态反应作用.中国药师,2005;8(1):5.
    [39]龙启才,邱建波.威灵仙、秦艽、桑寄生醇提物对外淋巴细胞和环氧酶的影响.中药药理与临床,2004;20(4):27.
    [40]慕妍琳,丛军兹.草决明的临床药用.牡丹江医学院学报,2006;27(6):60.
    [41]张朝辉,徐国钧,徐路珊,等.五种海马提取物对L-谷氨酸致大鼠神经钙内流的拮抗作用传代的影响.上海中医药杂志,1995;8:43.
    [42]许东辉,许实波.斑海马提取物抗血栓药理研究.中药材,1995;18(11):573.
    [43]高其铭,袁秉祥,赵苏玉,等.淫羊藿总黄酮对家兔血液流变学指标的影响.西安医科大学学报,1992;13(3):223.
    [44]李锐松.淫羊藿煎剂对健康人血小板聚集性的影响.中成药研究,1988;10(l):28.
    [45]王敏,刘崇铭,张金凤.淫羊藿甙扩张脑血管作用的研究.沈阳药学院学报,1991;8(4):273.
    [46]刘崇铭,王敏.淫羊藿黄酮对脑血流与脑缺血的作用.沈阳药科大学学报,1995;12(3):192.
    [47]陈文杰.淫羊藿的研究现状.甘肃中医,2007;20(5):68.
    [48]沈自尹,陈瑜,黄建华,等.EF处缓HPAT轴衰老的基因表达谱研究.中国免疫学杂志,2004;20(1):59-62.
    [49]蒋淑君,王桂兰,许兰芝.糖皮质激素对HPAA的影响及仙灵脾的调整作用.滨州医学院学报,2004;27(2):87-90.
    [50]王新陆.王新陆文集,上海:上海中医药大学出版社,2005,48-49.
    [51] Tamura A, Graham DI, Mc Culloch J, et al.Focal cerebral ischemia in the rat:1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion.J Cerb Blood Flow Metab, 1981; 1:15.
    [52] Shigeno T, Teasdale GM, Mcculloch J, et al.Recirculation model following MCA occlusion in rats.J Neurosurg, 1985; 63:272.
    [53] Markgraf CG, Kraydieh S, Prado R, et al.Comparative histopathologic consequences of photothrombotic occlusion of the pistal middle cerebral artery in Sprague-Damley and Wistar rats.Stroke, 1993; 24:286.
    [54] Koizumi J, Yoshida Y, Nagazawa T.Experimental studies of ischemic brain edemia:1. A new experimental embolism in rat in which recirculation can be introduced in the ischemic area.Jpn J Strode, 1986; 8:1.
    [55] Alexis NE, Dietrich WD, Green EJ, et al.Nonocclusive common carotid artery thrombosis in the rat results in reversible sensorimotor and cognitive behavioral deficits.Stroke, 1995; 26(12):2338.
    [56] Fuxe K, Kurosawa N, Cintra A, et al.Involvement of local ischemia in endothelin-1 induced lesions of the neostriatum of the anaesthetized rat.Exp Brain Res, 1992; 88(1):131.
    [57] Dirnagl V, Pulsinelli W.Autoregulation of Cerebral blood flow in experiment focal brain ischemia.J Cerebral blood Flow Metab, 1990; 10:327.
    [58]蒲传强,郎森阳,吴卫平.脑血管病学,北京:人民军医出版社,1999:95,101.
    [59] Mochizuki R, Takeda A, Sato N, et al.Induction of midkine expression in reactive astrocytes following rat transient forebrain ischemia.Exp Neurol, 1998; 149:73-88.
    [60]姚建平,金国琴.衰老神经内分泌免疫网络的中医药研究进展.中国中医药信息杂志,2004;11(12):1122.
    [61]郭静,张露芬,刘红,等.“贺氏三通法”对脑缺血再灌注大鼠模型血浆β-EP、ACTH的影响.北京中医,2007;26(6):381.
    [62] Moran O, Phillip M.Leptin: obesity, diabetes and other peripheral effects.Pediatr Diabetes, 2003; 4:101-109.
    [63]汪晓洲,马爱群,王军,等.正常大鼠中枢神经瘦素受体的分布.中华高血压杂志,2007;15(1):66.
    [64] Flier JS.What,s in a name? In search of leptin,s physiological role.J Clin Endocrinol Metab, 1983; 83: 1407-1413.
    [65] Heiman ML, Ahima RS, Craft LS, et al.Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress.Endocrinology, 1997; 138: 3859-3863.
    [66]周英,李明霞.瘦素与生长发育.国际儿科学杂志,2007;34(1):72.
    [67] Hosoi T, Okuma Y.Leptin regulates interleukin-1 beta expression in the brain via the STAT3 independent mechanisms.Brain Res, 2002; 949(1-2):139-146.
    [68]解建波,刘建民,陈玉芳.瘦素、炎性细胞因子与脑梗死.国外医学神经病学神经外科学分册,2003;30(5):460-461.
    [69]张冬梅,解建波,陈玉芳.瘦素、肿瘤坏死因子-α与脑梗死.中华神经科杂志,2003;36(4):287-288.
    [70]茅新蕾,张颖冬.缺血性脑卒中患者血浆胰岛素、瘦素水平的改变及其临床意义.临床神经病学杂志,2003;16(3):140-142.
    [71]解建波,陈玉芳.白细胞介素-6和瘦素与脑梗死.国外医学脑血管疾病分册,2002;10(5):380-382.
    [72]宫斌,莫启忠,莫志红,等.补肾中药对SRBC免疫大鼠脑和脾脏组织中神经递质含量的影响.中国免疫学杂志,1994;10(2):101.
    [73]姚鸿恩,刘坤,荣湘江.中枢性运动疲劳相关神经递质5-HT的研究进展.北京体育大学学报,2006;29(7):941.
    [74]韩济生主编.神经科学原理,北京:北京医科大学出版社,1999,9.
    [75]李继锋,王舟,纪祥瑞,等.5-HT在人正常淋巴结及淋巴瘤中表达的研究.中国免疫学杂志,2002;18:56-58.
    [76]孟云霄,谢琰臣.5-HT及其受体与神经免疫内分泌网络.临床与实验病理学杂志,2003;19(2):196.
    [77] Khan NA, Ferriere F, Deschaux P.Serotonin-induced calcium via 5-HT Ia receptors in Human Leuke mia (K562) cells.Cellul Immunol, 1995; 165:148.
    [78] Iken K, Cheng S, Fargin A, et al.Serotonin upregulate mitogen-stimulated Blymphocyte prolife ration through 5-HT Ia receptors.Cellul Immunol, 1995; 163:1.
    [79]赵勇,龚守良.5-羟色胺对小剂量辐射小鼠脾细胞免疫功能的影响.辐射研究与辐射工艺学报,1995;13(3):173-176.
    [80]姬仲.氟西汀对大鼠脑缺血再灌注损伤及离体海马神经元缺氧-复氧损伤的神经保护作用研究.第一军医大学博士学位论文,2004,30.
    [81]罗晓阳,张翔,王嘉军.纳洛酮对脑损伤大鼠血浆及海马匀浆中血管活性肠肽的影响.中国危重病急救医学,1996;8(11):641-642.
    [82]路长林.神经肽基础与临床,上海:第二军医大学出版社,2000,276.
    [83]王伟,席晔斌,王保国,等.血管活性肠肽对leydig细胞分泌的IL-1、IL-6和TGF-β的影响.免疫学杂志,2006;22(2):149.
    [84]陈丽萍.消化系统粘膜慢性炎症的神经免疫调节的形态学研究.吉林大学博士学位论文,2006,10.
    [85] Schroeter M, Jander S, HuitingaI, et al.Phagocytic response in photo chemically induced infarction of rat cerebral cortex.Stroke, 1997; 28:382-386.
    [86] Benjelloun N, Renolleau S, Represa A, et al.Inflammatory responses in the cerebral cortex after ischemia in the P7 neonatal rat.Stroke, 1999; 30:1916-1924.
    [87] Jander S, Kraemer M, Schroeter M, et al.Lymphocytic infiltration and expression no finter cellular adhesion molecule-1inphoto chemically induced ischemia of the rat cortex.J Cereb Blood Flow Metab, 1995; 15:42-51.
    [88] Kochanek PM, Hallenbeck JM.Polymorphonu clear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke, 1992; 23:1367-1379.
    [89] Kato H, Kogure K, Liu XH, et al.Progressive expression of immunomo leculeson activated microglia and invading leukocytes following focal cerebral ischemia in the rat.Brain Res, 1996; 734:203-212.
    [90]陈慰峰.医学免疫学,北京:人民卫生出版社,2000,94.
    [91]丁玄宙.应激对免疫功能的影响.生理科学进展,1989;20:265.
    [92]中山医科大学微生物教研室编.医学免疫学,2000,1-36.
    [93]林建雄,隋建峰,李希成,等.低氧大鼠海马脑片CA1区长时程增强的变化及ACTH的作用.中国病理生理杂志,2003;3:410-411.
    [94]陈泽斌,柯辉,邹锋.大鼠脑缺血再灌注后不同时间段中枢组织ACTH样蛋白表达变化.脑与神经疾病杂志,2006;14(1):26.
    [95]孟云霄,纪祥瑞.ACTH,ACTH-R与神经免疫内分泌网络.国外医学·生理、病理科学与临床分册,2002;22(4):391.
    [96]王舟,纪祥瑞.ACTH在神经免疫内分泌网络中的作用.济宁医学院学报,2002;25(4):59.
    [97]赵春艳,李占魁.雌二醇和睾酮与缺氧缺血性脑损伤的研究进展.国外医学妇幼保健分册,2004;15(1):7.
    [98]李怡,淑杰,路长林,等.胶质细胞介导性激素的神经系统作用.生理科学进展,2002;33:79-80.
    [99] Stone D J, Rozovsky I, Morgan T E, et al.Astrocytes and microglia respond to estrogen with increased ApoE mRNA in vivo and vitro.Experimental Neurology, 1997; 143(2):313-318.
    [100]赵春艳,李占魁.雌二醇和睾酮与缺氧缺血性脑损伤的研究进展.国外医学妇幼保健分册,2004;15(1):8.
    [101]徐晓阳,冯炜权,曹建民,等.运动性低血睾酮及补肾中药对大鼠能量代谢某些指标的影响.中国运动医学杂志,2000;19(3):282.
    [102]郭瑞新,蔡承妹,王惠芳,等.补肾中药对大鼠虚劳模型的作用.深圳中西医结合杂志,2002;12(4):197.
    [103]周志宏,刘建江.补肾益元中药对运动性疲劳肾气不足证及运动性低血睾酮的影响.中国运动医学杂志,2004;23(1):96.
    [104]杨秋美,钱汝红,庄剑青,等.肾虚与脑内雄激素受体关系的探讨.中国中医药科技,2006;13(2):68-69.
    [105] Kochanek PM, Hallenbeck JM.Polymorphonuclear leukocytes andmonocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke, 1992; 23:1367-1371.
    [106] Frijins CJ, Kappelle LI.Infalmmatory cell adhesion molecules in ischemic cerebrovascular disease.Stroke, 2002; 33:2115-2122.
    [107] Zhang RL, Chopp M, Jiang N, et al.Anti-intercellular adhesion molecule-1 antibody reduces ischemic cell damage after transient but not permanent middle cerebral artery occlusion in the Wistar rat.Stroke, 1995; 26:1438-1442.
    [108]雷万龙,袁群芳,姚志彬.环孢素A对实验性大鼠脑缺血治疗作用的组织化学研究.中山医科大学学报,2000;21(4S):60-63.
    [109]仓志兰,姜亚军.炎性细胞因子与缺血性脑卒中.临床荟萃,2005;20(11):654.
    [110]高剑峰,李建生.中医药对脑缺血损伤炎症级联反应干预研究现状.河南中医学院学报,2005;20(2):83.
    [111]岳寿伟.脑外伤后神经损伤修复的基础研究.现代康复,2001;5(12):5-6.
    [112]王国卿,杜景卫,夏作理.星形胶质细胞生物学功能和活化.泰山医学院学报,2005;26(2):185.
    [113] Niessen FB, Spauwen Phm, Schalkwijk J, et al.On the nature of hypertrophic scars and keloids: a review.Plast Recon Surg, 1999; 104(5):1435-1458.
    [114]程飚,付小兵,盛志勇.免疫因素在瘢痕形成和发展中的作用.中国临床康复,2002;6(4):472.
    [115]刘肃,吴延芳,刘成玉.免疫因素在瘢痕疙瘩发生发展中的作用研究.中华医学美容杂志,1999;5(1):18-21.
    [116]王德生,张守信.老年性痴呆,北京:人民卫生出版社,2001,253-262.
    [117]林文棠,朱平.实用临床免疫学,西安:第四军医大学出版社,2003,212.
    [118] Ricbardaom PM, McGuinness UM, Aguayo AJ.Axons from CNS neurons regenerate into PNS grafts.Nature, 1980; 284:264-265.
    [119]王晓芹,王一.胶质细胞与中枢神经的损伤和再生.中国临床康复,2005;9(25):179.
    [120] Badan I, Platt D, Kessler C. et al.Temporal dynamics of degenerative andregenerative events associated with cerebral ischemia in aged rats.Gerontology; 2003, 49(6):356-365.
    [121] Roelfsema V, Bennet L, George S, et al.Window of opportunity of cerebral hypothermia for postischemie white matter injury in the near-term fetal sleep.J Cereb Blood Flow Metab, 2004; 24(8):877-886.
    [122]徐国崇,李俐俐.偏瘫康复的理论与实践—偏瘫康复的理论基础.现代康复,2001;5(6):13.
    [123] Schwartzkroin PA.Mechamisms of brain plasticity: from normal brain function topathology.Int Rev Neurobiol, 2001; 45:1-15.
    [124]陈燕.脑髓-成脑中多能性神经干细胞存在的区域.生物化学与生物物理进展,2000;(2):122-123.
    [125]熊露,田少霞,范吉平,等.中医药治疗缺血性中风研究探讨.中医杂志,2004;45(1):5-7.
    [126]周永红.复健胶囊治疗缺血性卒中后遗症30例临床研究.中医杂志,2002;43(5):355-356.
    [127]周永红.复健片对MCAO大鼠脑内bFGF、VEGF、PDGF表达的影响.中医药学刊,2003;21(1):70-72.
    [128]王中琳.下调脑区激活及复健片作用机制研究.山东中医药大学博士学位论文,2003,33-40.
    [129]周永红.复健片促进缺血性卒中神经发生作用研究.山东中医药大学博士学位论文,2005,34-45.
    [130]朱舟,王伟,杨渝珍.胶质疤痕研究新进展.国外医学·物理医学与康复学分册,2004;24(3):136-139.
    [131] Ridet JL, Malhotra SK, Privat A, et al.Reactive astrocytes: cellular and molecular cues to biological function.TINS, 1997; 20:570-577.
    [132]方荃,马少林,董祥林.仙人掌提取物对兔耳增生性瘢痕组织块中胶原Ⅰ、Ⅲ及基质金属蛋白酶-1表达的影响.新疆医科大学学报,2007;30(6):571.
    [133]章昀,黄鉴政.基质金属蛋白酶与神经系统疾病.国外医学神经病学神经外科学分册,2002;29(2):140.
    [134]刘胜达.大鼠脑出血后脑组织MMP-2、MMP-9表达及其与脑水肿关系的研究.实用心脑肺血管病杂志,2007;15(4):251.
    [135] Nagase H, Woessner JF Jr.Matrix metalloproteinases.J Biol Chem, 1999; 274 (31): 21491-21494.
    [136]牛光明,万锋,李俊,等.MMP-2、TIMP-2在脑胶质瘤中的表达及其意义.中国临床神经外科杂志,2004;9(4):260.
    [137] Fujimura M, Gasche Y, Morita Fujimur Y, et al.Early appearance of activated matrix metalloproteinase-9 and blood-brain barrier disruption in mice after focal cerebral ischemia and reperfusion.Brain-Res, 1999; 842(1):92-100.
    [138]章昀,黄鉴政,闻树群,等.缺血性脑卒中血浆MMP-9的测定及临床意义.心脑血管病防治,2002;2(4):8.
    [139] Romanic AM, White RF, Arleth AJ, et al.Matrix metalloproteinase express increase after cerebral focal ischemia in rats: Inhibition of matrix metalloproteinases-9 reduces infarct size.Stroke, 1998; 29(8):1020-1030.
    [140] Colteon CA, Keri JE, Chen WT, et al.Protease production by cultured microglia: substrate gel analysis and immobilized matrix degradation.J Neurosci Res, 1993; 35:297-304.
    [141]周进.MMP-2及MMP-9在缺血再灌注大鼠脑中的表达及意义.辽宁医学杂志,2005;19(4):176.
    [142]杨永平,冯华,林江凯,等.大鼠脊髓损伤后胶质瘢痕形成情况的初步实验研究.中国医学研究与临床,2006;4(4):2.
    [143]林江凯.波形蛋白在胶质瘢痕形成中的作用——利用反义及正义波形蛋白逆转录病毒的研究.第三军医大学博士学位论文,2001,11.
    [144]赵雯,史景泉,卞修武,等.反义GFAP对人恶性胶质瘤细胞系CHG-5增殖及分化的影响.第三军医大学学报,2004;26(18):1622.
    [145] Petito CK, Morgello S, Felix JC, et al.The two patterns of reactive astrocytosis in postischemic rats brain.J Cereb Blood Flow Metab, 1999; 10(3):850-859.
    [146]张梁,毛善英,王伟,等.周期素依赖激酶抑制剂对大鼠局灶性脑梗死后胶质增生的影响.中华急诊医学杂志,2004;13(4):238.
    [147] Thomas F.Changes in the solubility of glial fibrillarv acidic protein after ischemic brain damage in the mouse.Neurochem, 1994; 63(5):1796.
    [148]李玉红,闫平,孟晓萍,等.实验性大鼠颅脑损伤后GFAP的表达研究.伤残医学杂志,2004;12(2):2.
    [149] Lin B, Ginsberg MD, Busto R, et al.Sequential analysis of subacute and chronic neuronal astrocytic and microglial alterations after transient global ischemia in rats.Acta Muropathol, 1998; 95(5):515.
    [150] Kim Y, Truettner J, Zhao W, et al.The influence of delayed postischemic hyperthermia following transient focal ischemia: alterations of gene expression. Neurol Sci, 1998; 159(1):1.
    [151] Mckeon RJ, Jurynec MJ, Buck CR.The chondrortin sulfate proteoglycans neurocan and phosphacan are expressed by reactive astrocytes in the chronic CNS glial scar.J Neurosci, 1999; 19(24):10778-10788.
    [152] Foumier AE, Grandpre T, Strittmatter SM.Identification of a receptor mediation Nogo-66 inhibition of axonal regeneration.Nature, 2001; 409(6818):341-346.
    [153] David S, Aguayo AJ.Axonal elongation into peripheral nervous system“bridges”after central nervous system injury in adult rats.Science, 1981; 214(4523): 931-933.
    [154] Zeng JS, Li H, Hong H.The synaptic reconstruction and expression of inhibitory protein in the thalamus and striatum after experimental cerebral infaction in rats. Zhongguo Linchuang Kangfu(Chin J Clin Rehabil), 2002; 6(17): 2534-2535.
    [155] Huber AB, Schwab ME.Nogo-A, a potent inhibitor of neurite outgrowth and regeneration.Biol Chem, 2000; 381(5-6):407-419.
    [1]赵敏,刘少君.中枢神经损伤后影响轴突再生的因素.生理科学进展,2004;35(2):107.
    [2]刘肃,吴延芳,刘成玉.免疫因素在瘢痕疙瘩发生发展中的作用研究.中华医学美容杂志,1999;5(1):18-21.
    [3]程飚,付小兵,盛志勇.免疫因素在瘢痕形成和发展中的作用.中国临床康复,2002;6(4):472-473.
    [4]蔡定芳,沈自尹.中西医结合神经内分泌免疫网络研究的思考.中国中西医结合杂志,1997;17(7):442.
    [5]季钟朴.现代中医生理学基础,北京:学苑出版社,1991,233.
    [6]李瀚.“肝肾同源”的理论探讨.中国中医基础医学杂志,2000;6(7):6.
    [7]任小巧,卢跃卿,郭秀珍,等.肝肾阴虚证与神经内分泌网络关系探讨.河南中医,1998;18(6):338-339.
    [8]陈燕.脑髓-成脑中多能性神经干细胞存在的区域.生物化学与生物物理进展,2000;(2):122-123.
    [9]熊露,田少霞,范吉平,等.中医药治疗缺血性中风研究探讨.中医杂志,2004;45(1):5-7.
    [1] Erikssonps, perfilievae, bjork-erikssont, et al.Neu-rogenesis in the adult human hippocampus.Nat Med, 1998; (4):1313-1317.
    [2]陈琳,龚珊,单立冬,等.单侧海马损毁诱发双侧齿状回细胞增殖的研究.苏州大学学报(医学版),2005;25(3):363-364.
    [3]汤锋武,韩忠朝.成体脑中神经发生障碍与干细胞治疗.国外医学?生理、病理科学与临床分册,2005;25(2):105.
    [4] Bulte JW, Zhang S, van-Gelderen P, et al.Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonace tracking of cell migration and myelination.Proc Natl Acad Sci USA, 1999; 96(26):15256-15261.
    [5] Chiasson BJ, Tropepe V, Morshead CM, et al.Adult mammalian forebrain ependymal and subependymal cells demonstrate proliferative potential, but only subependymal cells have neural stem cell characteristics.J Neurosci, 1999; 19(11):4462-4471.
    [6] Price J, Uwangho D, Peters S, et al.Neurotransplantation in neurode-generative disease: a survey of relevant issues in developmental neuro-biology.Novartis Found Symp, 2000; 231:148-165.
    [7] Kempermann G, Kuhn HG, Gage FH.Experience-induced neurogenesis in the senescent dentate gyrus.J Neurosci, 1998; 18:3206-3212.
    [8] Kempermann G, Kuhn HG, Gage FH.Genetic influence of neurogenesis in the dentate gyrus of adults mice.Proc Natl Acad Sci USA, 1997; 94:10409-10414.
    [9]李学坤,左萍萍.成体哺乳动物脑内的神经发生及其调节.中国康复理论与实践,2003;9(7):403.
    [10] Yagita Y, Kitagawa K, Ohtsuki T, et al.Neurogenesis by progenitor cells in the ischemic adult rat hippocampus.Stroke, 2001; 32(8):1890-1896.
    [11] Sopala M, Frankiewicz T, Parsons C, et al.Middle cerebral artery occlusion produces secondary, remote impairment in hippocampal plasticity of rats-involvement of N-methyl-D-aspartate receptors? Neurosci Lett, 2000; 281(2-3):143-146.
    [12] Kumiashi K, Uchida K, Miyazaki H, et al.Acetylsalicylic acid reduces ischemia-induced proliferation of dentate cells in gerbils.Neuroreport, 2001; 12(5): 915-917.
    [13] Ekdahl CT, Mohapel P, Elmer E, et al.Caspase inhibitors increase short-term survival of progenitor-cell progeny in the adult rat dentate gyrus following status epileptics.Eur J Neurosci, 200l; 14(6):937-945.
    [14]张建,胡远兵,杨忠,等.Wnt信号通路与神经发生.解剖科学进展,2005;11(3):258.
    [15] Benraiss A, Chmielnicki E, Lerner K, et al.Adenoviral brain-derived neurotrophic factor induce both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain.J Neurosci, 2001; 21:6718-6731.
    [16] Toda H, Takahashi J, Iwakami N, et al.Grafting neural stem cells improved the impaired spatial recognition in ischemic rats.Neurosci Lett, 2001; 316(1):9-12.
    [17] Cao YJ, Shibata T, Rainov NG.Liposome-mediated transfer of the bcl-2 gene results in neuroprotection after in vivo transient focal cerebral ischemia in an animal model.Gene Ther, 2002; 9:415-419.
    [1]韩济生主编.神经科学纲要,北京:北京医科大学、中国协和医科大学联合出版社,1993,123-196.
    [2]郑观成主编.脑老化与老年痴呆(第一卷)老年痴呆与系统工程,上海:上海科学技术文献出版社,1995.
    [3] O,dowd BS, Gibbs ME, Sedman GL.Brain Res Cohn.Brain Res, 1994; 2(2):93.
    [4] Shao Y, McCarthy KD.Plasticity of astrocytes.Glia, 1994; 11147-11155.
    [5]姚君茹,潘三强,吕来清.星形胶质细胞的可塑性.解剖学研究,2002;24(1):49.
    [6] Ridet JL, Malhotra SK, Privat A, et al.Reactive Astrocytes:cellular and molecular cues to biological function.TINS, 1997; 20:570-577.
    [7]刘之荣,段德新.星形细胞在缺血性脑损伤中的可能作用.国外医学·脑血管疾病分册,2000;8(3):148-150.
    [8]胡建军,洪庆涛,唐一鹏,等.天麻素对缺血再灌注损伤星形胶质细胞的保护作用及其对一氧化氮合成酶活性的影响.北京中医药大学学报,2001;24(5):11-15.
    [9] Koh JY, Choi DW.Quantitive determination of glutamate mediate cortical neuronal injury in cell culture by lactate dehydrogenase efflux Assay.J Neurosci Methods, 1987; 20(1):83-90.
    [10]邵小鹏,刘勇.川芎嗪对大鼠局部脑缺血星形胶质细胞的影响.交通医学,2001;15(4):362-364.
    [11]宋元宗,杨于嘉,贾延.黄芩甙对H2O2诱导星形胶质细胞NF-KB /IKBα表达的影响.中国当代儿科杂志,2002;4(6):436-439.
    [12]许汉鹏,王春婷,李静雯,等.芍药甙对体外培养大鼠星形胶质细胞活性的作用.解剖学报,2002;33(4):429-433.
    [13]王沙燕,赖真,耿小英,等.黄芪对脑缺血再灌注星形胶质细胞的影响.中国中医基础医学杂志,2003;9(4):41-43.
    [14]邓常青,王沙燕,王敏,等.补阳还五汤及其有效部位组方对沙土鼠脑缺血后反应性星形胶质细胞活化的影响.湖南中医学院学报,2001;21(4):5-8.
    [15] Jorgensen MB, Finsen BR, Jesen MB, et al.Microglial and Astroglial reactions to ischemic and kainic acid-induced lesions of the adult rat hippocampus.Exp Neurol, 1993; 120(1):70-88.
    [16]邓常青,邓奕辉,向华林,等.补阳还五汤及其有效部位对沙鼠脑缺血后DND脑能量代谢、NO和NOS的影响.中药药理与临床,1999;15(5):3-6.
    [17]邬力祥,言惠文,刘发益.参麦注射液对鼠脑星形胶质细胞缺氧/复氧损伤的保护作用.中国现代医学杂志,2002;12(7):3-5.
    [18]陈前芬,田鹤屯,杨卫东,等.参麦注射液对局部性脑缺血再灌注局部脑血流和脂质过氧化的影响.中国病理生理杂志,1996;12(4):376-440.
    [19]何丽云,孙塑伦.参麦注射液对神经细胞凋亡及脑浆钙变化的影响.中国中西医结合杂志,2001;21(8):605-607.
    [20]韩丽莎,马玉亭,韩哲.参麦注射液对缺血再灌注兔的保护作用.中国病理生理杂志,2000;7.
    [21]罗非群,钟林,尤家騄,等.参麦对内毒素诱导的小鼠腹腔巨噬细胞凋亡的保护作用.中国现代医学杂志,2001;11(1):12-14.
    [22] Geinisman Y et al.Hypertrophy of astroglial processes in the dentate gyrus of the senescent rat.Am J Anat, 1978; 153:537.
    [23] Hasan M and Glees P.Ultrastructural age changes in hipocampal neurons, synapses Exp.Gerontol, 1973; 8:75.
    [24] Palkovits M, Brownstein MJ.Locos Coeruleus.Advances in Cellular Neurobiology, 1983; 4:81.
    [25] Garrison CJ, Dougherty PM, Kajander KC, et al.Staining of glia fibrillary acidic protein(GFAP) in lumbar spinal cord increases following a sciatic nerve constriction injury.Brain Res, 1991; 565(1):1.
    [26] Ard MD, Bunge MB, Wood PM, et al.Retinal neurite growth on astrocytes is not modified by extracellular or matrx.anti-L; antibody or oligodendrocytes.Glia, 1991; 4(1):70.
    [27] Tarris RH, Weichsel ME, Fisher DA.Synthesis and secretion of a nerve growth-stimulating factor by neonatal mouse astrocyte cells on vitro.Ped Res, 1986; 20(4):367.
    [28] Komoly S, Hudson LD, Webster HD, et al.Insulin-like growth factor 1 gene expression is induced in astrocytes during experimental demyelination.Proc Natl Acad Sci USA, 1992; 89(5):1894. (此文已于《光明中医》发表,见2005;20(2):43-46)

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