摘要
目的探讨脑缺血再灌注损伤后神经调节素1β(NRG1β)对Cdk5信号通路中P35/P25表达和细胞凋亡的影响。方法成年健康雄性Wistar大鼠50只,假手术组(Sham组)10只,其余用线栓法建立大脑中动脉缺血再灌注损伤模型,将造模成功30只大鼠随机分为模型组(MCAO组)、治疗组(NRG组)和抑制剂组(Ros组),每组10只。NRG组和Ros组大鼠经颈内动脉分别注射NRG1β和Roscovitine各5μL进行干预治疗,Sham组和MCAO组大鼠注射0.1 mol/L PBS 5μL。用改良神经功能缺损评分(mNSS评分)测试大鼠神经功能,甲苯胺蓝染色观察神经细胞形态结构,TUNEL法检测细胞凋亡,免疫组化和Western blot方法检测神经细胞内P35/P25的表达。结果与Sham组比较,MCAO组mNSS评分显著升高,凋亡神经细胞数量增多,P35/P25表达显著增强;NRG组和Ros组大鼠神经细胞形态结构较MCAO组显著改善,mNSS评分下降,细胞凋亡减少;NRG组大鼠P35/P25表达较MCAO组显著下降,差异均有显著性(F=74.34~151.31,P<0.01)。NRG组与Ros组各指标比较差异均无显著性(P>0.05)。结论脑缺血再灌注损伤发生后,NRG1β可以抑制Cdk5信号通路中P35/P25的表达,减少神经细胞凋亡,发挥神经保护作用。
Objective To investigate the effect of neuregulin1β(NRG1β)on the expression of P35/P25 and apoptosis after cerebral ischemia/reperfusion injury in rats.Methods A total of 50 healthy male adult Wistar rats were selected,sham-oper-ation group(Sham group)10 rats,and the suture method was used to establish a model of middle cerebral artery ischemia/reperfusion injury.After successful modeling,30 rats were randomly divided into model group(middle cerebral artery occlusion(MCAO)group),treatment group(NRG group),and inhibitor group(Ros group),with 10 rats in each group.The rats in the NRG and Ros groups were given injection of NRG1β5μL and Roscovitine 5μL,respectively,via the internal carotid artery,and those in the Sham and MCAO groups were given injection of 0.1 mol/L PBS 5μL at the same time.Modified Neurological Severity Score(mNSS)was used to evaluate neurological function;toluidine blue staining was used to observe the morphological structure of neural cells;terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was used to measure cell apoptosis;immunohistochemistry and Western blot were used to measure the expression of P35/P25 in neural cells.Results Compared with the Sham group,the MCAO group had significant increases in mNSS score,neural cell apoptosis,and expression of P35/P25;compared with the MCAO group,the NRG group and the Ros group had significant improvement in the morphological structure of neural cells and significant reductions in mNSS score and cell apoptosis;compared with the MCAO group,the NRG group had a significant reduction in the expression of P35/P25(F=74.34-151.31,P<0.01).There were no significant differences in the above indices between the NRG group and the Ros group(P>0.05).Conclusion After cerebral ischemia/reperfusion injury,NRG1βcan exert a neuroprotective effect by inhibiting the expression of P35/P25 in the cyclin-dependent kinase 5 signaling pathway and reducing neural cell apoptosis.
作者
南宝
王悦
朱琳
刘翠
张睿
NAN Bao;WANG Yue;ZHU Lin;LIU Cui;ZHANG Rui(Institute of Integrative Medicine of Qingdao University Medical College, Qingdao 266021, China)
出处
《青岛大学学报（医学版）》
2021年第6期892-896,共5页
Journal of Qingdao University(Medical Sciences)
基金
青岛市博士后基金项目(2018-80)
青岛大学附属医院青年科研基金项目(2017Q0023)。
