摘要
目的探讨丙酮酸乙酯(EP)在局灶性脑缺血再灌注中的保护机制。方法雄性SD大鼠随机分成假手术组(Sham组)、缺血再灌注组(I/R组)和EP治疗组(EP组),线栓法制备大脑中动脉闭塞再灌注模型,EP组在脑缺血后即刻给予腹腔注射EP(40mg/kg),每隔12h注射1次。各组在缺血后24h断头取脑。HE染色观察组织病理学变化,免疫组化染色分别检测纹状体(Striatum)、皮质梗死区(CI)和皮质半暗带区(IP)中HMGB1及NF-κB的蛋白表达,RT-PCR法检测上述不同脑区的HMGB1mRNA水平。结果与I/R组相比,EP组梗死面积缩小,IP区组织、细胞损伤明显减轻,但对纹状体的损伤改善不明显。EP干预后不同脑区HMGB1和NF-κB的阳性细胞率均下降,以IP区下降尤为明显,但在Striatum区和CI区,两组间的蛋白表达无明显差异。EP也减少了IP区的HMGB1mRNA表达。结论 EP可能通过下调IP区HMGB1的基因和蛋白表达,抑制下游NF-κB活化,从而发挥脑保护作用。
Objective To investigate the neuroprotective mechanism of ethyl pyruvate （EP） following focal cerebral ischemia - reperfusion in rats. Methods The male Sprague - Dawley rats were randomly assigned to sham operation group （Sham） , ischemia - reperfusion group （I/R） and EP treatment group （ EP）. The middle cerebral artery of rat was occluded by using the intralumina] suture method and then recirculated. EP （40mg/kg） was immediately administered by intraperitoneal injection after cerebral ischemia and re- peated every 12 hours in EP group. 24 hours later, the rats were sacrificed and brain tissues were isolated. The histopathological damage were investigated with hematoxylin and eosin staining. The expression of HMGB1 and NF - κB was detected by immunobistochemistry in the striatum （Striatum）, cortical infarction （CI） and cortical penumbra （IP）. HMGB1 mRNA were also detected by RT- PCR tech- nique. Results Compared with I/R group, infarct size was reduced and the histopathologica] damage in penumbra was significantly amel- iorated in EP group, but no obvious improvement in striatal damage. In EP group,the positive cells rate of HMGB1 and NF - κB de- creased in different brain regions,especially in the cortical penumbra, hut no significant difference in the striatum and cortical infarction. Furthermore, the expression of HMGBlmRNA was also reduced in penumbra. Conclusion EP has a positive neuroprotective effect. It is assumed that the reduction of HMGB1 gene and protein expression in penumbra, subsequent inhibition of NF - κB activation play the role in the postischemic brain.
出处
《医学研究杂志》
2013年第2期140-144,共5页
Journal of Medical Research
基金
温州市科技局基金资助项目(Y20100286)
