丁苯酞注射液预处理对脑缺血大鼠出血转化及ERK5通路的影响

目的探讨丁苯酞注射液(NBP)预处理对脑缺血大鼠出血转化及细胞外信号调节激酶5(ERK5)通路的影响。方法将无特定病原体(SPF)级健康雄性SD大鼠随机分为假手术组、模型组、尼莫地平组8.0 mg/(kg·d)]、NBP低剂量组20 mg/(kg·d)]、NBP中剂量组40 mg/(kg·d)]、NBP高剂量组80 mg/(kg·d)];假手术组18只大鼠,其余组各20只大鼠。采用线栓插入进行脑缺血处理,尼莫地平组和NBP预处理组按照给药剂量进行腹腔注射,假手术组和模型组给予等量生理盐水,2 h后进行再灌注处理,24 h后评定大鼠神经功能。采用三苯基氯化四氮唑(TTC)法测定大鼠脑梗死面积,分光光度法测量脑切片中血红蛋白含量,苏木精-伊红(HE)染色观察大鼠脑组织出血情况,蛋白免疫印迹法检测大鼠脑组织MAP激酶激酶5(MEK5)、ERK5、肌细胞增强因子2C(MEF2C)蛋白表达量。结果与假手术组比较,模型组大鼠神经功能缺损评分、脑梗死面积、血红蛋白含量、出血点、脑组织p-ERK5/MEK5、p-ERK5/ERK5、p-MEF2C/MEF2C表达水平升高(P<0.05);与模型组比较,NBP各剂量组、尼莫地平组大鼠神经功能缺损评分、脑梗死面积、血红蛋白含量及出血情况降低(P<0.05),脑组织p-MEK5/MEK5、p-ERK5/ERK5、p-MEF2C/MEF2C蛋白表达水平升高(P<0.05),且NBP预处理组呈一定的剂量效应关系。结论NBP预处理对脑缺血再灌注大鼠具有一定的保护作用,可能与激活ERK5通路有关。

Effects of Butylphthalide Injection Pretreatment on Hemorrhage Transformation and ERK5 Pathway in Rats with Cerebral Ischemia

Objective To observe the effects of Butylphthalide Injection(NBP)pretreatment on hemorrhagic transformation and extracellular signal-regulated protein kinase 5(ERK5)pathway in rats with cerebral ischemia.Methods Specific pathogen free(SPF)grade male SD rats were randomly divided into sham operation group,model group,nimodipine group8.0 mg/(kg·d)],NBP low-dose group20 mg/(kg·d)],NBP medium-dose group40 mg/(kg·d)],NBP high-dose group80 mg/(kg·d)],with 18 rats in the sham operation group and with 20 rats in the other groups.Cerebral ischemia was treated with thread embolization,nimodipine group and NBP preconditioning groups were intraperitoneally injected according to the dosage,the sham operation group and model group were treated with the same amount of normal saline.After 2 hours with reperfusion,the neurological function of rats was evaluated after 24 hours.The area of cerebral infarction was detected by triphenyltetrazole chloride(TTC)method,the hemoglobin content of brain sections was detected by spectrophotometry,the cerebral hemorrhage of rats was detected by hematoxylin-eosin(HE)staining,and the protein expressions of MAP kinase kinase 5(MEK5),ERK5,and myocyte enhancer-binding factor 2C(MEF2C)in brain tissues of rats were detected by Western Blotting.Results Compared with the sham operation group,neurological deficit scores,the area of cerebral infarction,hemoglobin content,bleeding points,and expressions of p-ERK5/MEK5,p-ERK5/ERK5,and p-MEF2C/MEF2C in brain tissue of the model group were increased(P<0.05).Compared with the model group,neurological deficit scores,the area of cerebral infarction,hemoglobin content and bleeding points were decreased in the NBP treatment groups and nimodipine group,and protein expressions of p-MEK5/MEK5,p-ERK5/ERK5,and p-MEF2C/MEF2C in brain tissues were increased(P<0.05),and NBP pretreatment groups showed a certain dose-response relationship.Conclusion Butylphthalide Injection preconditioning possessed some protective effect on cerebral ischemia-reperfusion rats,which might be related to activation of ERK5 pathway.