刘启庭,崔寒尽,周华军,杨阿莉,唐涛

• 1:中南大学湘雅医院中西医结合研究所

摘要(Abstract)：

目的探讨补阳还五汤是否通过调节基质金属蛋白酶活性促进血管新生,为治疗脑出血探索新的思路。方法昆明种小鼠随机分为补阳还五汤组,模型组,多西环素组,补阳还五汤+多西环素组(联合组)。用Ⅶ胶原酶脑内立体定位注入小鼠右侧基底节内复制小鼠脑出血模型,14d后断头取脑,制成冰冻切片。采用免疫组化法检测血管内皮细胞的标志蛋白vWF,计数阳性微血管数。结果模型组阳性微血管数明显高于多西环素组;补阳还五汤组阳性微血管数明显高于模型组;补阳还五汤组阳性微血管数明显高于联合组。结论抑制MMPs活性将阻抑血管新生,补阳还五汤通过调节MMPS活性促进血管新生。

关键词(KeyWords)： 补阳还五汤;多西环素;脑出血;血管新生

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(No.30400581,30873221);; 湖南省自然科学基金(10JJ2023);; 湖南省中医药科技计划(2008016)

作者(Author): 刘启庭,崔寒尽,周华军,杨阿莉,唐涛

参考文献(References)：

• [1]杨小清.论补阳还五汤治疗中风病气虚血瘀证的作用机理[J].中国中医急症,2005,14(2):342-343.
• [2]何纲,金益强,黎杏群,等.脑溢安颗粒对脑出血大鼠脑内细胞间黏附分子-1表达和中性白细胞浸润及神经细胞损伤的影响[J].中国中西医结合杂志,2003,23(7):526-529.
• [3]Krupinski J,Kaluza J,Kumar P,et al.Role of angiogenesis in patientswith cerebral ischemic stroke[J].Stroke,1994,25(9):1794-1798.
• [4]Wayne Clark MD,Lisa Gunion-Rinker BS,Nikola Lessov PhD,et al.citicolinetreatmentforexperimentalintracerebralhemorrhageinmice[J].Stroke,1998,29:2136-2140.
• [5]Jian Wang,Stella E.Neuroprotection by inhibition of matrix metallo-proteinases in a mouse model of intracerebral haemorrhage[J].Brain,2005,128:1622-1633.
• [6]齐勇,唐涛,罗杰坤,等.益气活血法对脑出血大鼠脑内TSP-1、TSP-2及其受体CD36表达的影响[J].中国老年学杂志,2007,27(10):913-916.
• [7]刘宜峰,邢之华,唐涛,等.补阳还五汤对脑出血大鼠脑内Flt-1和Flk-1蛋白表达的影响[J].中国康复,2008,23(2):78-80.
• [8]阳鹤鹏,邢之华,唐涛,等.益气活血中药对脑出血大鼠脑组织Tie-2受体蛋白表达的影响[J].中国中医急症,2008,17(6):806-808.
• [9]虢灿杰.益气活血法对脑出血大鼠脑内Angiopoietin-1和受体Tie-2表达的影响[D].长沙:中南大学,2007.
• [10]王玲,唐涛,罗杰坤,等.补阳还五汤对脑出血大鼠脑内MMP-2表达的影响[J].中国老年学杂志,2007,27(13):1257-1260.
• [11]Golub LM,Lee HM,Ryan ME,et al.Tetracyclines inhibit connectivetissue breakdown by muhiple non-antimicrobial mecbanisms[J].AdvDent Res,1998,12(2):12-26.
• [12]Smith GN Jr,Brandt KD,Hasty KA.Activation of recombinant humanneutrophil procotlagenase in the presence of doxycyeline results infragmentation of the enzyme and loss of enzyme activity[J].ArthritisRheum,1996,39(2):235-244.
• [13]Uitto VJ,Firth J,Nip L,et al.Doxyeyeline and chemically modified te-traeyclines inhibit gelatinase A(MMP-2)gene expression in humanskin keratinocytes[J].Ann N Y Acad Sci,1994,732:140-151.
• [14]Hanemaaijer R,Visser H,Koolwljk P,et al.Inhibition of MMP synthe-sis by doxycyctine and chemically modified tetracyclines(CMTs)inhuman endothelial cells[J].Adv Dent Res,1998,12(2):114-118.
• [15]Ramamurthy NS,Veruillo AT,Greenwald RA,et al.Reactive oxygenspecies activate and tetracyclines inhibit rat osteoblast coltagenase[J].J Bone Miner Res,1993,8(4):1247-1253.
• [16]Schulze CJ,Wang W,Suarez-Pinzon WL,et al.Imbalance betweentissue inhibitor of metalloproteinase-4 and matrix metalloproteinasesduring acute myoctardial isehemia-repeffusion injury[J].Circulation,2003,107(i9):2487-2492.
• [17]Shlopov BV,Stuart JM,Gumanovskaya ML,et al.Regulation of carti-lage collagenase by doxycycline[J].J Rheumatol,2001,28(4):835-842.
• [18]Creemers EE,Cleutjens JP,Smits JF,et al.Matrix metalloproteinaseinhibition after myocardial infarction:a new approach to prevent heartfailure?[J].Circ Res,2001,89(3):201-210.
• [19]Xue M,Fan Y,Liu S,et al.Contributions of multiple protetmes 10neurotoxicity in a mouse model of intracerebral haemorrhage[J].Brain,2009,132(Pt 2):26-36
• [20]Garbett EA,Reed MW,Brown Nj,et al.Proteolysis in human breastand eolorectal cancer[J].Br J Cancer,1999,81(2):287-293.
• [21]Yang Y,Estrada EY,Thompson JF,et al.Matrix metaloproteinase-mediated disruption of tight junction proteins in cerebral vessels is re-versed by synthetic matrix metalloproteinase inhibitor in focal is-chemia in rat[J].J Cereb Blood Flow Metab,2007,27(4):697-709.
• [22]Hung YC,Chen TY,Lee EJ,et al.Melatonin decreases matrix metallo-proteinase-9 acfivation and expression and attenuates reperfusion-in-duced hemorrhage following tran,sient focal cerebral ischemia in rats[J].J Pineal Res,2008,45(4):459-467.