内质网应激预处理对大鼠局灶性脑缺血再灌注后听皮层损伤的保护作用

Protection effect of ERS pretreatment on the auditory cortex injury after focal cerebral ischemia-reperfusion injury in rats

目的探讨2-脱氧葡萄糖诱导内质网应激(ERS)预处理对大鼠局灶性脑缺血再灌注损伤后听力损伤的保护作用及机制。方法 SD大鼠随机分为假手术组(Sham组)、缺血再灌注组(I/R组)、ERS预处理组。采用线栓法制备大鼠大脑中动脉栓塞模型,脑缺血60 min,再灌注24 h。行神经功能评分,测定脑梗死体积,检测听性脑干反应,HE染色法观察听皮层神经元病理变化,末端标记法观察神经细胞凋亡状况。免疫组化法测定GRP78、Caspase-12蛋白表达。结果与Sham组比较,I/R组神经功能缺失评分升高,脑梗死体积增加,ABR反应阈值明显增加,HE染色正常组织结构消失,凋亡指数显著增加,GRP78、Caspase-12蛋白表达明显上升。与I/R组比较,ERS预处理组各项指标均有不同程度的改善。结论 ERS预处理可以减轻缺血再灌注损伤及细胞凋亡,减轻听力损伤。

Objective To study the mechanism of endoplamic reticulum stress（ERS）pretreatment induced by 2-DG on the auditory cortex injury after focal cerebral ischemia-reperfusion injury in rats.Methods The SD rats were randomly divided into 3 groups,sham group,I/R group,and ERS pretreatment group.Tread occlusion was used to prepare the model of MCAO in the mice for 60 min followed by reperfusion for 24 h.Neurological assessment was exercised and brain infarction volume was evaluated.The auditory brainstem response was tested.The pathological changes were observed by HE staining.Neurocyte apoptosis was observed by Tunel,and the apoptosis index（AI）was determined.Expression of GRP78 and Caspase-12 were detected by immunohistochemistry.Results Compared with the sham group,the neurological scores,ratio of infarct volume and the hearing thresholds in I/R group increased significantly.HE staining showed the normal structure disappeared,and apoptotic index increased significantly.Expression of GRP78 and Caspase-12 protein significantly up-regulated.Compared with I/R group,the indicators above showed improvement to some degrees.Conclusions The ERS pretreatment can alleviate the ischemia-reperfusion injury and neuron apoptosis in auditory cortex,and reduce the possibility of hearing loss.