摘要
目的:研究内质网应激(ERS)与脂联素的相关性及其在2型糖尿病缺血心肌易损性增强中的作用。方法:35只C57BL/6J雄性小鼠采用高糖高脂饮食联合链脲佐菌素(STZ)诱导2型糖尿病模型,按随机数字表法将糖尿病小鼠分为对照组(n=5)、牛磺脱氧胆酸(TUDCA)组(n=10)、毒胡萝卜内酯组(n=10)和生理盐水组(n=10)。对照组不做任何处理,其他三组在高糖高脂饲料喂养的最后3周,分别用TUDCA(250 mg/kg)、毒胡萝卜内酯(300μg/kg)和等量生理盐水腹腔注射给药,2次/天,连续给药3周后,TUDCA组、毒胡萝卜内酯组和生理盐水组各随机选取5只建立小鼠在体心肌梗死模型。心肌梗死72 h后,检测心肌梗死面积、血清脂联素含量、心肌组织中脂联素和凋亡相关蛋白C/EBP同源蛋白(CHOP)的含量及脂联素和CHOP mRNA表达水平。结果:TUDCA组及生理盐水组小鼠心肌梗死面积分别为(21.47±2.85)%和(39.92±4.28)%,均小于毒胡萝卜内酯组[(66.56±8.15)%,P均<0.01]。心肌梗死前,TUDCA组[(79.25±6.40)pg/ml]和生理盐水组[(70.23±4.15)pg/ml]血清脂联素浓度均高于毒胡萝卜内酯组[(62.64±5.70)pg/ml,P均<0.01],各组小鼠心肌梗死前血清脂联素浓度均高于心肌梗死72 h时浓度;各组小鼠心肌组织中脂联素含量及mRNA表达水平检测结果与血清脂联素检测结果一致,而CHOP含量及mRNA表达水平检测结果则与之相反。结论:2型糖尿病导致的心肌缺血损伤加重与ERS相关;ERS可能在2型糖尿病心肌易损性增强中起着重要作用,ERS加重后通过下调脂联素水平,增加了2型糖尿病心肌易损性。
Objective： To study the relationship between endoplasmic reticulum stress （ERS） and adiponectin; to explore the role of ERS for increasing myocardial ischemic vulnerability in type 2 diabetes mellitus （DM） mice. Methods： Type 2 DM model was established by high fat diet with streptozotocin （STZ） injection. A total of 35 C57BL/6J male type 2 DM mice were divided into 4 groups： （1） Control group, n=5. （2） Tauroursodeoxycholic acid （TUDCA） group, （3） Thapsigargin （TG） group and （4） Normal saline group. The mice in Groups （2） , （3） , （4） were fed by high fat and high glucose diet by injecting strcptozotocin （STZ）, in the last 3 weeks and respectively received intraperitoneal injections of TUDCA （250 mg/kg）, thapsigargin （TG） （300 μg/kg） and normal saline twice a day, n=10 in each group. Then myocardial infarction （MI） model was established in 5 mice from each group. 72 hours later, the MI ranges were measured, serum levels of adiponectin were detected, mRNA expressions of adiponectin and CHOP in myocardial tissue were examined. Results： The MI range in TUDCA group （21.47 ± 2.85） % and in Normal saline group （39.92 ± 4.28） % were both lower than TG group （66.56 ± 8.15） %, both P〈0.01. Before MI occurrence, serum levels of adiponectin in TUDCA group （79.25 ± 6.40） pg/ml and in Normal saline group （70.23 ± 4.15） pg/ml were both higher than TG group （62.64 ± 5.70） pg/ml,both P〈0.01; serum levels of adiponectin in each group were higher than they were 72 h after MI. In each group, the mRNA expression and protein content of adiponectin in myocardial tissue were constant to serum adiponectin; while the mRNA expression and protein content of CHOP was opposite to serum adiponectin. Conclusion： ESR could increase myocardial vulnerability in type 2 DM mice which might be related to down-regulating adiponectin expression.
出处
《中国循环杂志》
CSCD
北大核心
2016年第1期91-95,共5页
Chinese Circulation Journal
基金
湖北省教育厅自然科学研究项目(D20121309)
国家自然科学基金面上项目(81270280)
关键词
糖尿病
2型
内质网
心肌缺血
Diabetes mellitus, Type 2
Endoplasmic reticulum
stress
Myocarial ischemia
