厄贝沙坦对糖尿病大鼠心肌纤维化的影响及其潜在机制.docVIP

厄贝沙坦对糖尿病大鼠心肌纤维化的影响及其潜在机制 何继瑞张晓敏，徐坤，李洁（兰州大学第二医院内分泌与代谢临床医学中心，VIP糖尿病科，甘肃 兰州 730030） 探讨对2型糖尿病大鼠心肌纤维化的影响及可能机制。方法 30只雄性Wistar大鼠随机分为正常对照组（N组）、糖尿病组（D组）组（组），每组10只，对照组大鼠给予常规饲料喂养，糖尿病组和组大鼠采用高脂高糖饲料喂养，6周后给予对照组大鼠3ml柠檬酸缓冲液腹腔注射，而其余大鼠予以腹腔注射链脲佐菌素（30mg/kg）制备2型糖尿病大鼠模型。造模成功后，大鼠mg/kg灌胃一次，大鼠予以等量生理盐水灌胃。8周后所有大鼠处死，称重，计算心重指数。实时荧光定量PCR法测定心肌局部TGF-β1、Smad3、Smad7 mRNA水平，免疫组化法测定TGF-β1、Smad3、Smad7蛋白水平，透射电镜下观察大鼠心肌超微结构，Masson染色测定心肌胶原含量。结果 ①与对照组组比较，糖尿病组、组大鼠心肌胶原含量增多，心重指数增加，心肌纤维化明显，TGF-β1、Smad3表达明显升高，而Smad7表达降低（P＜0.01）。②经干预后，糖尿病大鼠心重指数、心肌胶原含量较糖尿病未干预组显下降，TGF-β1、Smad3表达下降，Smad7表达有所升高（P＜0.05），心肌纤维化程度减轻。结论 具有减轻糖尿病大鼠心肌纤维化的作用，其作用可能TGF-β1/Smads 信号通路。β1；smad3；smad7 中图分类号：R587.1Abstract:Objective To study the effects of Irbesartan on myocardial fibrosis in diabetes rats and its potential mechanism. Methods 30 male Wistar rats were randomized into three groups:normal group（group N）,diabetes group（group D）and diabetes treated with Each group include ten rats.The group N was fed with standard rat diet, six weeks later, 3ml of 基金项目：甘肃省中医药管理局普通科研项目（GZK-2011-26） 作者：，州大学第二医院内分泌与代谢临床医学中心，VIP糖尿病科，0030 citrate buffer solution was administered by peritoneal injection.Meanwhile,the group D and group I received a high fat diet for six weeks and a 30mg/kg streptozotocin peritoneal injection to induce T2DM model. After the success of modeling,group I received a once-daily dose of 30mg/kg Irbesartan intragastric administration for eight weeks,the rest diabetes rats received the same amount of saline solution.Animals were sacrificed eight weeks after injection.All rats were weighed and the heart weight-to-body weight ratio(H/B) was calculated. The levels of TGF-β1,Smad3,Smad7 mRNA in myocardium were determined by Real-time quantitative PCR.Meanwhile,the protein expression of TGF-β1,Smad3,Smad7 was determined by immune histochemistry.Myocardial pathologic changes were observed by transmission electronic microscope.Masson staining was used to detect the volume fraction of myocardial collagen.Rerults ①The levels of myocardial