替罗非班对急性缺血性卒中大鼠PI3K/Akt/e NOS通路及神经损伤的影响

Effects of Tirofiban on PI3K/Akt/eNOS Pathway and Nerve Injury in Rats with Acute Ischemic Stroke

目的探讨替罗非班对急性缺血性卒中大鼠磷脂酰肌醇-3-激酶/丝氨酸-苏氨酸激酶/内皮型一氧化氮合酶(PI3K/Akt/eNOS)及神经损伤的影响。方法选取150只雄性Wista大鼠作为研究对象,由浙江大学动物实验中心提供,根据治疗方式将大鼠分为假手术组、模型组及治疗组,各50只;治疗组于灌注前30 min尾静脉注射60μg/kg替罗非班,假手术组、模型组尾静脉注射等量生理盐水;比较三组肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、血浆肌钙蛋白Ⅰ(cTnⅠ)、心肌梗死面积、p-Akt、Akt、eNOS相关指标水平。结果模型组CK-MB、LDH、cTnⅠ及心肌梗死面积均高于假手术组、治疗组,差异有统计学意义(P<0.05);治疗组p-Akt、p-eNOS、p-Akt/Akt以及p-eNOS/eNOS水平均高于假手术组及模型组,且模型组的p-Akt、p-eNOS、p-Akt/Akt及p-eNOS/eNOS水平均高于假手术组,差异有统计学意义(P<0.05);三组Akt以及eNOS水平比较,差异无统计学意义(P>0.05)。结论替罗非班用于急性缺血性卒中,可激活PI3K/Akt/eNOS通路活性,减轻大鼠的神经功能损伤。

Objective To explore the effects of tirofiban on phosphatidylinositol-3-kinase/serine-threonine kinase/endothelial nitric oxide synthase(PI3K/Akt/eNOS)and nerve damage in rats with acute ischemic stroke.Methods A total of 150 male Wista rats were selected as the research objects,which were provided by Animal Experimental Center of Zhejiang University.According to the treatment methods,the rats were divided into sham operation group,model group and treatment group,with 50 rats in each group.The treatment group was treated with intravenous injection of 60μg/kg tirofiban 30 min before perfusion,and the sham operation group and the model group were treated with intravenous injection of the same amount of saline.The levels of creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),plasma troponinⅠ(cTnⅠ),myocardial infarction area,p-Akt,Akt and eNOS related indicators were compared among the three groups.Results The CK-MB,LDH,c TnⅠand myocardial infarction area in the model group were higher than those in the sham operation group and the treatment group,and the difference was statistically significant(P<0.05).The levels of p-Akt,p-eNOS,p-Akt/Akt and p-eNOS/eNOS in the treatment group were higher than those in the sham operation group and the model group,and the levels of p-Akt,p-eNOS,p-Akt/Akt and p-eNOS/eNOS in the model group were higher than those in the sham operation group,the difference was statistically significant(P<0.05).There was no significant difference in Akt and eNOS levels among the three groups(P>0.05).Conclusion In acute ischemic stroke,tirofiban can activate PI3K/Akt/eNOS pathway activity and alleviate neurological damage in rats.