芍药苷对急性脑梗死大鼠小胶质细胞激活调节的神经元焦亡的作用

Effect of paeoniflorin on neuronal pyrotosis induced by microglia activation inrats with acute stroke

目的研究芍药苷对急性脑梗死(ACI)大鼠神经元焦亡的影响。方法36只SD大鼠随机分为3组,假手术组、脑缺血组、芍药苷组(10mg·kg^(-1)),每组12只。中动脉急性脑缺血造模前连续给药1w,再灌注24h后检测神经功能,取脑组织用于免疫荧光、免疫组化及免疫印迹检测。结果急性脑缺血-再灌注成功造成大鼠神经功能损伤,缺血区梗死显著;脑中小胶质细胞激活显著,神经元焦亡明显;炎性小体(NLRP3)活化增加,胱冬肽酶-1(Caspase-1)与白细胞介素-1β(IL-1β)表达上调;与脑缺血组相比,芍药苷组大鼠神经功能评分显著降低(P<0.05),脑梗死面积显著减少(P<0.05),Iba1表达显著下调(P<0.05)且神经元状态显著改善(P<0.05);此外,芍药苷组NLRP3、Caspase-1与IL-1β表达显著减少(P<0.05)。结论芍药苷通过抑制NLRP3与Caspase-1活化,减少小胶质细胞激活,抑制神经元焦亡,改善ACI介导的神经功能损伤。

Objective To study the effect of paeoniflorin on neuronal pyrolysis in acute cerebral infarction(ACI)rats.Methods 36 SD rats were randomly divided into 3 groups,Sham group,Cerebral ischemia group,Paeoniflorin group(10 mg·kg^(-1)),12 rats in each group.Before the acute cerebral artery occlusion operation,paeoniflorin was continuously administered for one week.Neurological scores were detected 24 hours after reperfusion and brain tissues were taken for immunofluorescence,immunohistochemistry,and immunoblotting.Results Acute ischemiareperfusion successfully caused neurological damage in rats and increased infarct area;Activation of microglia in the brain and neuronal pyrolysis were significant increased;In addition,the expressions of inflammasome(NLRP3),Caspase-1 and interleukin-6(IL-1β)were up-regulated;Compared with cerebral ischemia group,the neurological scores of the paeoniflorin group were significantly reduced(P<0.05),the infarct area was significantly decreased(P<0.05),the expression of Ibal was significantly down-regulated(P<0.05),and the neuron status was significantly improved(P<0.05);In addition,the expression of NLRP3,Caspase-1 and IL-1βin the paeoniflorin group was significantlydown-regulated(P<0.05).Conclusion Paeoniflorin can reduce the activation of microglia,inhibit the pyrolysis of neurons by inhibiting the activation of NLRP3 and Caspase-1,and improve the neurological damage mediated by ACI.