三七总皂苷对脑缺血再灌注损伤大鼠缺氧诱导因子1α和基质金属蛋白酶表达的影响

Effect of Panax notoginseng saponin on expression of HIF-1α,MMP-2 and MMP-9 in rats after cerebral I/R injury

目的观察三七总皂苷(PNS)对脑缺血再灌注损伤大鼠血脑屏障损伤相关蛋白缺氧诱导因子1α(HIF-1α)、基质金属蛋白酶(MMP)-2和MMP-9表达的影响。方法选择SD大鼠130只,分为PNS组(60只)、模型组(60只)和假手术组(10只),PNS组于再灌注后给予尾静脉注射PNS 18mg/(kg·d),模型组和假手术组以等体积生理盐水替代。观察PNS组和模型组大鼠7d存活率。再灌注24h取材(每组10只),以脑组织HE和尼氏染色观察缺血半暗带神经元形态以及核心区神经元存活数,以ELISA法检测半暗带皮质HIF-1α、MMP-2及MMP-9蛋白表达水平。结果模型组神经元数量较假手术组明显减少[(190.0±59.4)个/mm2 vs(582.5±31.2)个/mm2,P<0.01];PNS组神经元数量较模型组显著增加[(372.5±41.1)个/mm2 vs(190.0±59.4)个/mm2,P<0.01]。模型组缺血再灌注24h MMP-2、MMP-9和HIF-1α水平显著高于假手术组(P<0.05,P<0.01);PNS组缺血再灌注24h MMP-2、MMP-9和HIF-1α水平显著低于模型组,差异有统计学意义(P<0.01)。结论 PNS对短暂性大脑中动脉闭塞模型大鼠缺血再灌注损伤早期起到神经元保护作用。

Objective To study the effect of Panax notoginseng saponin（PNS）on expression of HIF-1α,MMP-2and MMP-9in rats after cerebral I/R injury.Methods One hundred and thirty SD rats were divided into PNS group（n=60）,model group（n=60）,and sham operation group（n=10）.The rats in PNS group were treated with PNS（18mg/kg·d）after reperfusion,those in model group and sham operation group were treated with physiological saline and their 7-day survival rate was recorded.Ten animals from each group were sacrificed at 24 hafter reperfusion.The morphology of ischemic penumbra neurons was observed and the number of surviving neurons in core area was calculated with HE and Nissl staining.The expression of HIF-1α,MMP-2,MMP-9in penumbra cortex was detected by ELISA.Results The number of neurons was significantly less in model group than in sham operation group and much more in PNS group than in model group（P〈0.01）.The expression level of MMP-2,MMP-9,and HIF-1αwas significantly higher in model group than in sham operation group and significantly lower in PNS group than in model group at 24 hafter reperfusion（P〈0.05,P〈0.01）.Conclusion PNS can protect rats with transient MCAO against early I/R injury.