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作 者 ：黄小平,谭华,陈北阳,邓常清

期 刊 ：中国中药杂志 2010年 35卷 16期 页码：2187.

关键词：黄芪总苷；三七总皂苷；脑缺血再灌注；基质金属蛋白酶-9；组织基质金属蛋白酶抑制物-1；

Keywords:cerebral ischcmia, reperfusion damage, astragalosides, Panax notoginseng saponins, matrix metalloproteinases-9, tissue inhibitor of meta11oproteinase-1,

摘 要 ：目的: 研究黄芪总苷(AST)和三七总皂苷(PNS)配伍对小鼠脑缺血再灌注后脑组织基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)与组织基质金属蛋白酶抑制物-1(tissue inhibitor of meta11oproteinase-1,TIMP-1)表达的影响,探讨其抗缺血性脑损伤的保护机制。 方法 : C57BL/6N小鼠随机分成假手术组、模型组、AST和PNS配伍高、中、低剂量组、AST单用组、PNS单用组及依达拉奉组,连续给药4 d后结扎双侧颈总动脉20 min,再灌注24 h,建立脑缺血再灌注模型,用HE染色检测海马区病理形态,用Western-blot法检测MMP-9与TIMP-1蛋白在脑组织的表达。 结果 :各药物组神经元存活率显著高于模型组(P<0.01),以配伍中剂量组作用显著,析因分析表明AST(110 mg·kg^-1)与PNS(115 mg·kg^-1)配伍具有协同的交互作用(P<0.01)。各药物组脑组织MMP-9蛋白表达显著低于模型组(P<0.01或P<0.05),而TIMP-1的表达显著高于模型组(P<0.05或P<0.01),且以配伍中剂量组作用显著,两药配伍均具有叠加的交互作用(P<0.05)。 结论 :AST 110 mg·kg^-1与PNS 115 mg·kg^-1配伍具有协同抗脑缺血再灌注损伤的作用,其机制可能与调节缺血脑组织MMP-9,TIMP-1的蛋白表达有关。

Abstract:Objective : To investigate the effect of astragalosides(AST) and Panax notoginseng saponins(PNS) compatibility on the expression of matrix metalloproteinases-9(MMP-9) and tissue inhibitor of meta11oproteinase-1 (TIMP-1) after cerebral ischemia/reperfusion(I／R) injury in mice, to probe into its anti-ischemic brain injury protection mechanism. Method :C57BL／6N mice were randomly divided into sham-operation group, model group, AST and PNS compatibility of high, medium and low-dose group, AST group, PNS group and edaravone group.Cerebral ischemia-reperfusion injury were prepared by bilateral common carotid artery ligation for 20 min followed by 24 hours reperfusion after administration for 4 days. Pathomorphism was detected with HE staining and the expression of MMP-9 and TIMP-1 protein in brain was detected by western-blot. Result : The neuronal survival rate in the drug groups was significantly higher than the control group(P<0.01), and the effect of the-middle dose compatibility group was more obvious. Factorial analysis manifested that AST110 mg·kg^-1 and PNS115 mg·kg^-1 compatibility had a synergistic interaction(P<0.01). The expression of MMP-9 protein in the drug groups was lower than the model group significantly(P<0.01 or P<0.05), but the expression of TIMP-1 protein was higher than the model group significantly(P <0.01 or P<0.05), and the effect of the-middle dose compatibility group was more obvious, the two drugs had the stacking interaction (P<0.05). Conclusion :AST110 mg·kg^-1 and PNS115 mg·kg^-1 compatibility has a synergistic effect against ischemia-reperfusion injury in mice by accommodating MMP-9／TIMP-1 probably.

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