葫芦巴碱对脑梗死大鼠认知障碍及氧化应激损伤的影响  

Impacts of trigonelline on cognitive impairment and oxidative stress injury in rats with cerebral infarction

作　　者：陈静 周慧敏 钟纯正 王御林 Chen Jing;Zhou Huimin;Zhong Chunzheng;Wang Yulin(Department of Neurology,Danzhou People's Hospital,Danzhou 571799,Hainan Province,China)

机构地区：[1]儋州市人民医院神经内科,571799

出　　处：《中华老年心脑血管病杂志》2023年第6期643-647,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：海南省卫生健康行业科研项目[琼卫科教(2020)9号]。

摘　　要：目的基于沉默信息调节因子1(Sirt1)/叉头框蛋白O1(FoxO1)通路探究葫芦巴碱对脑梗死大鼠认知障碍及氧化应激损伤的影响。方法90只SD大鼠,随机选取18只大鼠为假手术组,其余大鼠采用线栓法建立脑梗死模型,造模后分为模型组、葫芦巴碱低剂量(低剂量)组(葫芦巴碱50 mg/kg)、葫芦巴碱高剂量(高剂量)组(葫芦巴碱100 mg/kg)、葫芦巴碱+EX-527组(100 mg/kg葫芦巴碱+5 mg/kg Sirt1特异性抑制剂EX-527),每组18只;另取18只大鼠为假手术组。采用生化法检测脑组织丙二醛含量和超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性;Western blot检测Sirt1、FoxO1、乙酰化FoxO1(Ac-FoxO1)蛋白表达。结果与假手术组比较,模型组逃避潜伏期、神经功能缺损评分、海马神经元凋亡指数、活性氧阳性细胞数、丙二醛、Ac-FoxO1蛋白水平明显升高,在目标象限中的时间、穿越平台次数、SOD和GSH-Px活性以及Sirt1、FoxO1蛋白水平明显降低(P<0.05);与模型组比较,低剂量组和高剂量组神经功能缺损评分[(1.96±0.27)分、(1.34±0.25)分vs(2.45±0.31)分]、海马神经元凋亡指数[(23.80±2.65)%、(11.97±2.04)%vs(34.52±4.19)%]明显降低(P<0.05)。结论葫芦巴碱可能通过激活Sirt1/FoxO1信号通路,抑制氧化应激和神经元凋亡,改善脑梗死后认知功能障碍。Objective To explore the impacts of trigonelline(TG)on cognitive impairment and oxidative stress injury in rats with cerebral infarction based on the Sirt1/FoxO1 pathway.Methods A total of 90 SD rats were randomly divided into sham operation group,model group,and low-and high-dose TG groups(50 and 100 mg/kg TG),and TG+Sirt1 specific inhibitor EX-527 group(100 mg/kg TG+5 mg/kg EX-527),with 18 animals in each group.Biochemical assay were used to measure the content of MDA and activities of SOD and GSH-Px in brain tissue.Western blotting was adopted to detect the protein levels of Sirt1,FoxO1 and acetylated FoxO1(Ac-FoxO1).Results Compared with the sham operation group,the model group had longer escape latency,and higher NDS,apoptotic index of hippocampal neurons,count of ROS-positive cells,MDA content,and Ac-FoxO1 level(P<0.05),while shorter time in the target quadrant,and lower times of platform crossing,SOD and GSH-Px activities,and protein levels of Sirt1 and FoxO1(P<0.05).Low and high TG treatment resulted in lower NDS(1.96±0.27 and 1.34±0.25 vs 2.45±0.31)and apoptotic index of hippocampal neurons[(23.80±2.65)% and(11.97±2.04)%vs(34.52±4.19)%]when compared with the model group(P<0.05).Conclusion TG may inhibit oxidative stress and neuronal apoptosis by activating Sirt1/FoxO1 signaling pathway,and thus improve cognitive dysfunction after cerebral infarction.

关 键 词：胡芦巴碱 脑梗死 叉头框蛋白O1 认知障碍 

分 类 号：R285.5[医药卫生—中药学]