糖尿病血糖漂移下内质网应激对海马神经元的影响  

Influence of endoplasmic reticulum stress response on hippocampus cell fate by fluctuating hyperglycemia

作　　者：周晓雨[1] 任明山[1] 吴元洁[2] 

机构地区：[1]安徽医科大学附属省立医院神经内科,合肥230001 [2]安徽中医学院中医基础教研室,合肥230038

出　　处：《安徽医科大学学报》2013年第9期1036-1040,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81102626)

摘　　要：目的研究内质网应激通路相关蛋白在糖尿病血糖漂移状态下对糖尿病大鼠海马CA1区神经元的影响,探讨波动性高血糖加重糖尿病脑组织损伤可能的发病机制。方法 65只SD大鼠随机分为正常对照组(n=15)和糖尿病模型组(n=50),糖尿病模型组以1%链尿佐菌素腹腔注射法造模。将造模成功的46只糖尿病模型组大鼠随机分为持续高血糖组(n=20)和波动高血糖组(n=26),波动高血糖组制作血糖漂移模型。波动造模6周后统计各组大鼠每日血糖平均水平(MBG)、每日血糖平均水平的标准差(SDBG)、最大血糖波动幅度(LAGE)。用免疫组化法观察海马CA1区肌醇依赖的跨膜蛋白激酶1(IRE1)和Bcl-2表达情况,用Western blot法测定海马组织CCAAT/增强子结合蛋白同源蛋白(CHOP)、葡萄糖调节蛋白78(GRP78)表达情况。结果波动高血糖组的SDBG、LAGE明显高于正常对照组及持续高血糖组(P<0.05),MBG低于持续高血糖组及正常对照组(P<0.05)。波动高血糖组IRE1、CHOP、GRP78表达较持续高血糖组及正常对照组明显升高(P<0.05);Bcl-2表达较持续高血糖组、正常对照组显著下降(P<0.05)。结论糖尿病血糖漂移状态促进海马神经元内质网过度应激从而加重损伤。Objective To explore the effects of intermittent glucose on endoplasmic reticulum stress pathway（ERS） related protein in diabetic rat hippocampal CA1 neurons and to investigate possible pathways of fluctuating hyperglycemia aggravated damage in rat hippocampus.Methods Sixty-five 10 weeks old male SD rats were randomly assigned into two groups： the normal group（n = 15） and the diabetic mellitus group（n = 50）.The diabetic group were given 1% STZ intraperitoneal injection to make experimental diabetes mellitus.The successful ones were randomly assigned into two groups： intermittent high glucose group（n = 26） and sustained high glucose group（n = 20） when intermittent ones established fluctuating high blood glucose modes.All rats were executed after intervening for 6 weeks,then the expression levels of inositol requiring ER-to-nuclous signal kinase 1（IRE1） 、Bcl-2、 CCAAT / enhancer-binding protein homologous protein（CHOP）,78 ku glucose-regulated protein（GRP78） were detected by immunohistochemical method and Western blot,while the average blood glucose levels（MBG）,the standard deviation of daily average blood glucose（SDBG） and the largest amplitude of glycemic excursions（LAGE） were mearsured at the same time.Results The SDBG,LAGE of intermittent glucose group significantly rised（P 0.05） compared with normal group and diabetic group.The MBG of diabetic group was higher than the other groups（P 0.05）.The expression of IRE1,CHOP,GRP78 of intermittent glucose group were obviously higher than both sustained high glucose group and normal group while the level of Bcl-2 was much more reduced（P 0.05）.Conclusion The fluctuating hyperglycemia could promote hippocampal neurons ERS so as to increase damage.

关 键 词：血糖漂移 内质网应激 海马 

分 类 号：R587.25[医药卫生—内分泌]