尼可地尔对大鼠冠状动脉微栓塞后心肌细胞凋亡的影响及其潜在机制

Effects of nicorandil on myocardial apoptosis after coronary microembolization in rats and its potential mechanism

目的探讨尼可地尔(NIC)对大鼠冠状动脉微栓塞(CME)后心肌的影响及相关机制。方法48只SD大鼠随机分为3组:A组(假手术组)、B组(CME组)、C组(CME+NIC组),每组16只。B、C组建立CME模型,C组大鼠利用NIC溶于生理盐水,术前按照3mg/(kg·d)灌胃给药,A组和B组大鼠给以等量生理盐水。一周后取出各组大鼠心肌组织,TUNEL染色法观察心肌组织,流式细胞仪检测心肌细胞凋亡数量,实时定量荧光PCR及Westernblot检测NF-E2相关因子2(Nrf2)及血红素加氧酶1(HO-1)表达,酶联免疫吸附(ELISA)检测心肌组织Caspase-3表达。结果B组大鼠心肌凋亡细胞数显著高于A组,而C组显著低于B组,差异有统计学意义(P<0.05)。B组大鼠Nrf2及HO-1表达显著低于A组,而C组Nrf2及HO-1表达明显高于B组,差异有统计意义(P<0.05)。B组心肌组织Caspase-3表达显著高于A组,C组大鼠心肌组织Caspase-3表达显著低于B组,差异有统计学意义(P<0.05)。结论NIC可通过上调Nrf2/HO-1信号通路抑制CME后大鼠心肌细胞凋亡。

Objective To explore the effects of nicorandil on myocardial apoptosis after coronary microembolization and to explore the potential mechanism.Methods 48 SD rats were averagely divided into 3 groups,including group A(the sham group),group B(CEM group),and group C(CME+NIC group).Apoptotic cells were observed by TUNEL method and flow cytometry at 7th day.Nrf2 and HO-1 expression were detected by real-time PCR and western blot.Meanwhile,the caspase-3 activity was valued by elisa.Results Apoptotic cells in group B were significantly higher than those in group A,while those in group C were markedly lower than those in group B(P<0.05).Nrf2 and HO-1 expression in group B were significantly lower than those in group A,and which in group C were effectively higher than those in group B(P<0.05).Besides,caspase-3 expression in group B was markedly higer than that in group A,and which in group C was significantly lower than that in group B(P<0.05).Conclusion Nicorandil could protect myocardial apoptosis after coronary microembolization probably via Nrf2/HO-1 pathway.