APP17肽对糖尿病性脑病大鼠胰岛功能、脂代谢、神经炎症和认知障碍的影响  

Effects of APP17peptide on islet function,lipid metabolism,neuroinflammation and cognitive impairment in diabetic encephalopathy rats

作　　者：刘丽君[1] 王睿君 苗燕平[1] LIU Lijun;WANG Ruijun;MIAO Yanping(Department of Imaging Diagnosis,The Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,China;Inner Mongolia Clinical Medical Research Center of Nervous System Diseases,Hohhot 010050,China)

机构地区：[1]内蒙古医科大学附属医院影像诊断科,内蒙古呼和浩特010050 [2]内蒙古自治区神经系统疾病临床医学研究中心,内蒙古呼和浩特010050

出　　处：《中国实验诊断学》2024年第7期830-835,共6页Chinese Journal of Laboratory Diagnosis

基　　金：内蒙古自治区高等学校科学研究项目(NJZY23151,NUZY23151);内蒙古自治区自然科学基金(2017MS0833);内蒙古自治区科技计划(2019GG9044);内蒙古自治区神经系统疾病临床医学研究中心项目资助。

摘　　要：目的探讨APP17肽对糖尿病病大鼠血糖、脂质代谢、认知障碍和神经炎症因子的影响。方法将Wistar大鼠分为对照组、模型组(DE组)和低、高剂量实验组。除对照组外,各组采用链脲佐菌素诱导Ⅰ型糖尿病脑病大鼠模型。造模成功后,低和高剂量实验组分别灌胃给予0.05μg/kg和0.15μg/kg的APP17肽,对照组和模型组均灌胃等量0.9%NaCl,每天1次,连续灌胃2周。检测大鼠的血糖及糖耐水平;水迷宫实验分析各组认知障碍;酶联免疫吸附试验检测血清脂代谢和炎症因子TNF-a及IL-10;Western blotting检测各组鼠海马组织中突触和神经相关蛋白PSD95,NGF及及内质网应激相关蛋白eIF-2α,CHOP表达水平的影响。结果与DE组相比,APP17处理实验组小鼠的血糖及血清胰岛素水平明显降低(P<0.05);脂代谢脂代谢指标TC,TG和LDL-C浓度明显降低,HDL-C浓度增高(P<0.05);改善了大鼠认知功能和学习记忆能力;减少了促炎因子TNF-a及IL-10水平(P<0.01);增加了PSD95,NGF蛋白表达;抑制了eIF-2α,CHOP蛋白表达。结论APP17肽有效改善糖尿病性脑病胰岛功能,抑制炎症,缓解认知障碍。Objective To investigate the effects of APP17 peptide on blood glucose, lipid metabolism, cognitive impairment and neuroinflammatory factors in diabetic rats.Methods Wistar rats were divided into control group, model group(DEgroup),low dose experimental group and high dose experimental group.Except for the control group, streptozotocin was used to induce type I diabetic encephalopathy rat model.After the model was successfully established, the low and high dose experimental groups were given 0.05 and 0.15 μg/kg APP17 peptide by gavage, respectively, and the control and model groups were given the same amount of 0.9%NaCl by gavage once a day for 2 weeks.Blood glucose and glucose tolerance were measured.The water maze experiment analyzed the cognitive impairment of each group.Serum lipid metabolism and inflammatory factors TNF-a and IL-10 were detected by enzyme-linked immunosorbent assay.Western blotting detected the effects of synaptic and nerve-related proteins PSD95,NGF,and ER stress-related proteins eIF-2α and CHOP expression levels in hippocampal tissues of each group.Results Compared with DE group, blood glucose and serum insulin levels in APP17 group were significantly decreased(P<0.05).Lipid metabolism, the concentrations of TC,TG and LDL-C were significantly decreased, while HDL-C were significantly increased(P<0.05).The cognitive function and learning and memory ability of rats were improved.The levels of pro-inflammatory factors TNF-a and IL-10 were decreased(P<0.01).The expression of PSD95 and NGF protein was increased.The expression of eIF-2α and CHOP protein was inhibited.Conclusion APP17 peptide can effectively improve the islet function of diabetic encephalopathy, inhibit inflammation and relieve cognitive impairment.

关 键 词：糖尿病性脑病 APP17 血糖 脂质代谢 炎症 认知障碍 

分 类 号：R587.1[医药卫生—内分泌]