盐酸戊乙奎醚对高氧所致幼鼠脑损伤时Shh/Gli1信号通路的影响  

Effect of penehyclidine hydrochloride on Shh/Gli1 signaling pathway during hyperoxia-induced brain injury in infantile rats

作　　者：颜莉丽[1] 陈燕[1] 程闪[1] 董铁立[1] 袁峰[1] YAN Lili;CHEN Yan;CHENG Shan;DONG Tieli;YUAN Feng(The Second Affiliated Hospital of Zhengzhou University,Zhengzhou 450003,China)

机构地区：[1]郑州大学第二附属医院,河南郑州450003

出　　处：《中国实用神经疾病杂志》2020年第9期743-748,共6页Chinese Journal of Practical Nervous Diseases

基　　金：河南省医学科技攻关计划项目(编号:2018020156)。

摘　　要：目的探讨盐酸戊乙奎醚对高氧所致幼鼠脑损伤时Shh/Gli1信号通路的影响。方法健康清洁级14 d龄Sprague-Dawley(SD)幼鼠共30只,按照随机数字表法分为3组对照组(C组)、高氧组(HO组)和高氧+盐酸戊乙奎醚组(HP组),每组10只。从造模第一天起,HP组幼鼠给予盐酸戊乙奎醚剂量为0.3 mg/kg,于每日同一时间点给药,共计7 d。C组和HO组均于相同时间点给予等容量的生理盐水。实验结束后进行神经功能缺损评分(NDS)。留取幼鼠海马并测定湿/干质量比(W/D)。光镜下观察海马CA1区病理学改变。原位末端标记法(TUNEL)测定海马CA1区细胞凋亡情况并计算细胞凋亡指数(AI)。免疫荧光法观察海马CA1区Shh和Gli1表达部位,蛋白免疫印迹法分别检测海马Shh和Gli1蛋白表达水平。结果与C组比较,HO组幼鼠NDS、海马W/D、AI均升高(P<0.05),海马CA1区正常锥体细胞计数减少(P<0.05)。HP组幼鼠NDS、海马W/D、AI均较HO组降低(P<0.05),海马CA1区正常锥体细胞计数较HO组增多(P<0.05)。HO组幼鼠海马形态学结构发生明显损伤,HP组幼鼠海马形态学结构损伤有不同程度的减轻。与C组比较,HO组幼鼠海马Shh和Gli1表达水平均升高(P<0.05)。HP组幼鼠海马Shh和Gli1表达水平均较HO组升高(P<0.05)。结论盐酸戊乙奎醚对高氧所致脑损伤发生的幼鼠脑组织具有保护作用,其机制可能与激活Shh/Gli1信号通路有关。Objective To investigate the effect of penehyclidine hydrochloride Shh/Gli1 signaling pathway during hyperoxia-induced brain injury in infantile rats.Methods Thirty healthy infantile Sprague-Dawley(SD)rats aged 14 days of clean grade were randomly allocated into 3 groupscontrol group(C group),hyperoxia group(HO group)and hyperoxia plus penehyclidine hydrochloride group(HP group),10 mice per group.From the first day of modeling,infantile rats were injected intravenously with penehyclidine hydrochloride(0.3 mg/kg)at the same time point for continuous seven days in HP group.Infantile rats were injected with equal volume normal saline at the same time point in C group and H group.Neurological deficit score was tested after experimental time out.Infantile rats were euthanized,and the hippocampus was excised.Wet hippocampus weight to dry hippocampus weight(W/D)was tested.Pathological changes of the hippocampus CA1 were observed by light microscope.The change of hippocampal apoptosis and apoptotic index(AI)were determined by TdT-mediated dUTP nick end labeling(TUNEL)method.The expression site of Shh and Gli1 in hippocampus CA1 area were observed by immunofluorescence.The expression levels of Shh and Gli1 were determined by Western blot.Results Compared with C group,NDS,W/D and AI in the hippocampus were all notably higher(P<0.05)in HO group,and the normal pyramidal cell counts in the hippocampal CA1 region were decreased(P<0.05).NDS,W/D and AI of the hippocampus in HP group were all lower(P<0.05)than those in HO group,and the normal pyramidal cell counts in the hippocampal CA1 region were increased(P<0.05)in HP group.The morphology of lung tissue was more apparently injured in HO group.The injury of morphology of lung tissue was more alleviated in HP group.Compared with C group,the expression levels of Shh and Gli1 in hippocampus of HO group were increased(P<0.05).The expression levels of Shh and Gli1 in hippocampus of HP group were higher than those in HO group(P<0.05).Conclusion Penehyclidine hydrochloride has a prote

关 键 词：盐酸戊乙奎醚 Sonic hedgehog GLI1 细胞凋亡 脑损伤 高氧 幼鼠 

分 类 号：R-332[医药卫生]