黄芪总苷和三七总皂苷配伍对脑缺血再灌注后MMP-9和TIMP-1表达的影响

Influence of astragalosides and Panax notoginseng saponins compatibility on MMP-9 and TIMP-1 after cerebral ischemia-reperfusion in mice

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 met-alloproteinase-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:AST110 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。

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（P0.01）,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（P0.01）.The expression of MMP-9 protein in the drug groups was lower than the model group significantly（P0.01 or P0.05）,but the expression of TIMP-1 protein was higher than the model group significantly（P 0.01 or P0.05）,and the effect of the-middle dose compatibility group was more obvious,the two drugs had the stacking interaction（P0.05）.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.