摘要
目的探索二甲双胍对糖尿病大鼠认知功能障碍的保护作用,探讨p38 MAPK/ATF2信号通路的作用。方法30只SD大鼠随机分成空白组、模型组及二甲双胍组,每组10只。除空白组外均给予高糖高脂饲料,50 d后腹腔注射链脲佐菌素(STZ,30 mg/kg)建立2型糖尿病脑病模型。模型制备成功后,二甲双胍组大鼠腹腔注射100 mg/kg二甲双胍,连续给药6周,空白组和模型组给予等体积蒸馏水。Morris水迷宫检测各组大鼠认知能力;HE染色观察海马区形态学变化;TUNEL染色检测神经元凋亡;Western blot检测凋亡相关蛋白Bax、Bcl-2、Cleaved-caspase3以及p38 MAPK、p-p38 MAPK、ATF2蛋白的表达情况。结果二甲双胍组大鼠逃避潜伏期明显缩短,目标象限停留时间延长,穿越平台次数相应增加,海马区神经细胞结构改善、神经元凋亡数量显著降低,Bax/Bcl-2比值和Cleaved-caspase3蛋白表达水平显著降低,二甲双胍还能够抑制p-p38 MAPK、ATF2蛋白的表达。结论二甲双胍改善糖尿病大鼠认知功能,与抑制p38 MAPK/ATF2信号通路有关。
Objective To explore the protective effect of metformin on cognitive dysfunction via p38 MAPK/ATF2 signaling pathway in diabetic rats.Methods Thirty SD rats were randomly divided into blank group,model group and metformin group(100 mg/kg for 6 weeks),10 in each group.The high-sugar and high-fat feed was given,and streptozotocin(STZ,30 mg/kg)was intraperitoneally injected 50 days later to establish a type 2 diabetic encephalopathy model.Morris water maze was used to detect the cognitive ability of rats.HE staining was used to observe the morphological changes of hippocampus.TUNEL staining was used to detect neuronal apoptosis.Western blot was used to detect apoptosisrelated proteins Bax,Bcl-2,Cleared-caspase3 and p38 MAPK,p-p38 MAPK,ATF2.Results In the metformin group,escape latency was significantly shorter,residence time in the target quadrant was longer,and the number of crossing platforms was increased,neuronal cell structure in the hippocampus was improved,the neuronal apoptosis rate in the hippocampus was decreased,Bax/Bcl-2 ratio and Cleared-caspase3 expression level were significantly reduced.The expression of p-p38 MAPK and ATF2 protein was inhibited.Conclusion Metformin improves the cognitive function of diabetic rats,which is related to the inhibition of p38 MAPK/ATF2 signaling pathway.
作者
杨立新
衣小龙
陶翠
高文君
陈克研
YANG Li-xin;YI Xiao-long;TAO Cui;GAO Wen-jun;CHEN Ke-yan(The First Department of Cadre,Affiliated Central Hospital of Shenyang Medical College,Shenyang 110024;Department of Laboratory Animals,China Medical University,Shenyang 110122,China)
出处
《解剖科学进展》
CAS
2022年第1期31-34,38,共5页
Progress of Anatomical Sciences
基金
沈阳市科技局课题(19-112-4-034)。
