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 APP17 peptide on islet function,lipid metabolism,neuroinflammation and cognitive impairment in diabetic en-cephalopathy rats
刘丽君 1王睿君 2苗燕平1
作者信息
- 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
- 折叠
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0.05 μg/kg和0.15 μg/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肱有效改善糖尿病性脑病胰岛功能,抑制炎症,缓解认知障碍.
Abstract
Objective To investigate the effects of APP17 peptide on blood glucose,lipid metabolism,cognitive im-pairment 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,strepto-zotocin 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.Ser-um 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 concen-trations 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 diabet-ic 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Key words
Diabetic encephalopathy/APP17 peptide/Lipid metabolism/Inflammation/Cognitive impairment引用本文复制引用
基金项目
内蒙古自治区高等学校科学研究项目(NJZY23151)
内蒙古自治区高等学校科学研究项目(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()
出版年
2024
NETL
NSTL
万方数据