Ⅱ型糖尿病大鼠脑血管Aβ1-42也沉积的病理特点及其与ApoE的相关性研究  

Pathological features of Aβ1-42 deposition and its correlation with ApoE in the brain of streptozotocin-induced type II diabetic rats

作　　者：王雅琳 赵张宁[2] 马高亭[2] 李帅[2] 朱梅佳[2] 

机构地区：[1]山东大学临床医学院神经病学,济南250012 [2]山东大学附属千佛山医院神经内科,济南250014

出　　处：《中华神经医学杂志》2017年第7期676-681,共6页Chinese Journal of Neuromedicine

基　　金：（1）基金项目：山东省自然科学基金（ZR2010L1M101）（2）基金项目：济南市科技发展计划项目（201202053）

摘　　要：目的探讨Ⅱ型糖尿病大鼠脑血管B．淀粉样蛋白1-42（Aβ1-42）沉积的病理特点及其与载脂蛋白E（ApoE）的相关性。方法以高脂饲料联合小剂量链脲佐菌素（STZ）诱导制作Ⅱ型糖尿病大鼠模型并设为糖尿病组．采用随机数字表法将其分为糖尿病3月龄组（n=15）、糖尿病6月龄亚组（n=151。以未干预的健康大鼠作为正常组，采用随机数字表法将其分为正常3月龄亚组（n=15）、正常6月龄亚组（n=15）。采用免疫组化染色观察各亚组大鼠脑组织内Aβ1-42ApoE分布部位及表达量．采用实时荧光定量PCR、Western blotting检测ApoEmRNA及蛋白表达。结果免疫组化染色显示：Aβ1-42在Ⅱ型糖尿病大鼠脑微血管壁内、微血管周围均有聚集分布。正常6月龄亚组与正常3月龄亚组相比，糖尿病6月龄亚组与糖尿病3月龄亚组相比，Aβ1-42ApoE阳性染色细胞数、血管数均明显增多，ApoE mRNA及蛋白相对表达量均明显增高，差异均有统计学意义（P〈0．05）。糖尿病6月龄亚组与正常6月龄亚组相比，糖尿病3月龄亚组与正常3月龄亚组相比，Aβ1-42ApoE阳性染色细胞数、血管数均明显增多，ApoEmRNA及蛋白相对表达量均明显增高，差异均有统计学意义（P〈0．05）。Person相关性分析显示大鼠Aβ1-42阳染细胞数与ApoE蛋白相对表达量呈正相关（r=0．9755，P=0．000）。结论Aβ1-42在Ⅱ型糖尿病大鼠脑内呈现微血管壁内、微血管周围均有沉积的病理特点；年龄增长和糖尿病病程延长能够增加Aβ1-42及ApoE在脑组织内表达，且两者存在正相关关系。Objective To explore the pathological features of Aβ1-42 deposition and its correlation with Apolipoprotein E in brain of streptozotocin （STZ）-induced type II diabetic rats. Methods High fat diet combined with small dose of STZ induced diabetic rats were adopted as experiment rats, and randomly divided into 3 months old diabetes mellitus group and 6 months old diabetes mellitus group （n=15）. Healthy Wistar rats were adopted as control rats, and divided 3 months old control group and 6 months old control group （n=15）. The Aβ1-42 and ApoE location and expressions were detected by immunohistochemistry. Real-time fluorogenic quantitative-PCR and Western blotting were used to detect the mRNA and protein levels of ApoE in each group. Results Immunohistochemical results showed that Aβ1-42 in the brain of the diabetic rats gathered around the vessel wall and blood vessel. The number of Aβ1-42 and ApoE positively-stained cells and positively-stained vessels was significantly larger and the ApoE mRNA and protein expressions were significantly increased in the 6 months old diabetes mellitus group as compared with those in the 3 months old diabetes mellitus group （P〈0.05）. The number of Aβ1-42 and ApoE positively-stained cells and positively-stained vessels was significantly larger and the ApoE mRNA and protein expressions were significantly increased in the 6 months old control groupas compared with those in the 3 months old control group （P〈0.05）. As compared with that in the 6 months old control group, the number of Aβ1-42 and ApoE positively-stained cells and positively-stained vessels was significantly larger and the ApoE mRNA and protein expressions were significantly increased in the 6 months old diabetes mellitus group （P〈0.05）. As compared with that in the 3 months old control group, the number of Aβ1-42 and ApoE positively-stained cells and positively-stained vessels was significantly larger and the ApoE mRNA and protein expressions was significantly increased in the 3 months ol

关 键 词：β-淀粉样蛋白1-42 载脂蛋白E Ⅱ型糖尿病 

分 类 号：R587.1[医药卫生—内分泌]