布南色林通过激活PI3K/AKT/GSK3β信号通路对精神分裂症大鼠海马神经元损伤的影响  

Effects of Blonanserin on hippocampal neurons damage in schizophreniarats by activating PI3K/AKT/GSK3βsignaling pathways

作　　者：徐晓津[1] 房茂胜[1] 缪楹 黎维勇 Xu Xiaojin;Fang Maosheng;Miao Ying;Li Weiyong(Dept of Psychiatry,Wuhan Mental Health Center,Wuhan 430012;Dept of Pharmacy,Union Hospital of Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022)

机构地区：[1]武汉市精神卫生中心精神科,武汉430012 [2]华中科技大学同济医学院附属协和医院药学部,武汉430022

出　　处：《安徽医科大学学报》2022年第11期1801-1806,共6页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:8217131142);武汉市卫生和计划生育委员会科研项目(编号:WX18D32)。

摘　　要：目的探究布南色林对MK-801诱导精神分裂症大鼠海马神经元损伤及PI3K/AKT/GSK3β信号通路的影响。方法采用MK-801诱导精神分裂症模型,将48只SD大鼠随机分为正常组、模型组、布南色林组(1 mg/kg布南色林)、利培酮组(0.54 mg/kg利培酮)。通过刻板行为、旷场实验和Morris水迷宫实验观察大鼠行为学,用HE染色观察大鼠海马组织病理损伤并评分,检测血清糖脂代谢指标水平,实时荧光定量PCR和免疫印迹法检测海马组织磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(AKT)、糖原合成酶激酶3β(GSK3β)mRNA和蛋白表达。结果与模型组比较,布南色林组和利培酮组刻板行为评分、旷场实验总路程、逃避潜伏期及海马组织病理损伤评分降低;穿越平台原位置次数,PI3K、AKT、GSK3βmRNA,PI3K、AKT和GSK3β磷酸化水平升高(P<0.05);但布南色林组和利培酮组上述指标的比较,差异无统计学意义。正常组、模型组和布南色林组空腹血糖(FPG)、糖化血红蛋白(HbA1c)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)及低密度脂蛋白(LDL)水平的比较,差异无统计学意义,但利培酮组FPG、HbA1c、TG及TC水平较其他三组升高(P<0.05),HDL和LDL水平差异无统计学意义。结论布南色林可能通过激活PI3K/AKT/GSK3β信号通路对精神分裂症大鼠海马神经元损伤发挥神经保护作用,改善其认知功能和学习记忆能力。Objective To explore the effects of Blonanserin on hippocampal neurons damage and PI3K/AKT/GSK3βsignaling pathways in rats with MK-801 induced schizophrenia.Methods The schizophrenia models were induced by one-time intraperitoneal injection of MK-801.A total of 48 SD rats were randomly divided into normal group,model group,Blonanserin group(1 mg/kg Blonanserin)and risperidone group(0.54 mg/kg risperidone),with 12 cases in each group.The behaviors of rats were observed by stereotyped behavior assay,open field test and Morris water maze.The pathological damage of hippocampus was observed by HE staining,which was scored.The levels of serum glucose-lipid metabolism indexes were detected.The mRNA and proteins of phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT)and glycogen synthase kinase 3β(GSK3β)in hippocampal tissues were detected by real-time fluorescent quantitative PCR and Western blot.Results Compared with model group,scores of stereotyped behaviors,total distance in open field test,escape latency and score of pathological damage in hippocampus decreased in Blonanserin group and risperidone group,while times of crossing platform original site,levels of PI3K,AKT and GSK3βmRNA,and phosphorylation levels of PI3K,AKT and GSK3 increased(P<0.05).However,there was no significant difference in the above indexes between Blonanserin group and risperidone group.The differences in levels of fasting blood glucose(FPG),glycosylated hemoglobin(HbA1c),triglyceride(TG),total cholesterol(TC),high-density lipoprotein(HDL)and low-density lipoprotein(LDL)among normal group,model group and Blonanserin group was not statistically significant.However,levels of FPG,HbA1c,TG and TC in risperidone group were higher than those in the other three groups(P<0.05),and there was no significant change in HDL or LDL.Conclusion Blonanserin may protect schizophrenia rats from hippocampal neurons damage,improve cognitive function,learning and memory ability by activating PI3K/AKT/GSK3βsignaling pathways.

关 键 词：布南色林 精神分裂症 PI3K/AKT/GSK3β信号通路 认知功能 学习记忆 糖脂代谢 

分 类 号：R971.41[医药卫生—药品]