神经调节素对大鼠脑缺血损伤的预防性治疗作用和机制

目的探讨神经调节素（NRG-1 β）对大鼠脑缺血损伤的预防性治疗作用和机制。方法Wistar大鼠150只，应用线栓法建立大鼠大脑中动脉闭塞（MCAO）模型，随机分为对照组和治疗组，在MCAO前经颈内动脉注射NRG-1 β（2μg/kg）进行预防性治疗。在MCAO后0h、0．5h、1．0h、1．5h和2．0h分别用干湿重法测定脑组织含水量，氯化三苯基四氮唑（TYC）染色测定脑梗塞体积，细胞凋亡用末端脱氧核苷酸转移酶介导的生物素脱氧尿嘧啶核苷酸缺口末端标记（TUNEL）法，早期生长反应基因-1（Egr-1）表达水平用免疫组化检测。结果大脑中动脉阻断后，动物脑组织含水量和梗塞面积随着缺血时间的延长而逐渐增加，NRG预处理组脑组织含水量低于对照组，梗塞范围也明显缩小。脑缺血可诱导脑组织细胞凋亡和Egr-1表达，随着缺血时间的延长，凋亡细胞和Egr-1阳性细胞数明显增多；NRG预处理能明显减少缺血诱导的细胞凋亡数，增加Egr-1的表达水平。结论NRG-1 β可能通过抑制凋亡途径和诱导Egr-1表达水平，对缺血性脑损伤具有积极的保护作用。

The preventive therapeutic effect and mechamsm of neuregulin on cerebral ischemic injury in rats

Objective To evaluate the preventive therapeutic effects of neuregulin-1β(NRG-1β)on ischemic cerebral insult in rats and to probe into its mechanism.Methods One hundred and C,fty healthy Wistar rats were subjected to establish middle cerebral artery occlusion(MCAO)raxtel by intraluminal thread,and randomly divided into the control and the pretreatment group.NRG-1β(2μg/kg)was adnfimstrated into the imemal candid artery (ICA)in tlle pretreatment group before MCAO.At the interval of either 0 h,0.5 h,1 h,1.5 h or2 h after MCAO operation,the brain water content was expressed as the percentage change using wet and dry weight method,and the cerebral infarction volume was detected with tetrazolium chloride(TIE)stain.The apoptosis were determined by terrmnal dcoxynueleotidyl transference-mediated biotinylated nick end labeling technique(TUNEL.)and early growth response gone-1(Esr-1)by immunohistochemical assay.Paesults After MCAO,the brain water content and the cerebral infarction volume was increased successively according to the ischemic time.NRG-1β pretreatment could decrease the two parameters compared with the control group at the same timepoint.Simultaneously,the cerebral ischemia could induce the apoptosis and expression of Egr-1 in braintissue.Withinthe duration ofischemic time,the number of apoptoticcells and Esr-1 positive cells increased gradually.NRG-1β pretreatment could obviously decnease the amount of apoptotic cells and increase the expression level of Egr-1 protein.Conclusion NRG-1β,might play a crucial neuroprotective effect in ischemic cerebral insult through inhibiting apoptosis and activating some early gene expression.