曲尼司特对STZ糖尿病大鼠心肌的保护作用  

The Protective Effects of Tranilast on Cardiomyopathy in Diabetic Rats

作　　者：姜宇[1] 符丽娟[1] 

机构地区：[1]辽宁医学院药理学教研室,辽宁锦州121000

出　　处：《辽宁医学院学报》2013年第4期4-7,I0001,I0002,共6页Journal of Liaoning Medical University (LNMU) Bimonthly

基　　金：辽宁省科技计划项目;编号:2011225015

摘　　要：目的观察曲尼司特(tranilast,Tra)对糖尿病心肌纤维化及转化生长因子-β1表达的影响,探讨其对糖尿病心肌的保护作用及机制。方法健康SD大鼠40只,随机取10只为正常对照组(NC),余30只一次性给予链脲佐菌素30 mg.kg-1.尾静脉注射制备糖尿病大鼠模型。随机分为糖尿病模型组(DM)、曲尼司特低剂量组(Tra1)及高剂量组(Tra2)(100、200 mg/(kg.d))各10只。饲养12周,测定血糖、心脏质量指数(HMI);Masson染色观察心肌形态学变化,测算心肌胶原容积分数(CVF);免疫组织化学法检测心肌TGF-β1蛋白表达水平。结果与NC组相比,DM组大鼠血糖、HMI明显增高(P<0.01),+dp/dtmax和-dp/dtmax显著降低(P<0.01);与DM组相比,HMI明显下降(P<0.01),+dp/dtmax、-dp/dtmax显著升高(P<0.05)。DM组大鼠心肌肌纤维排列紊乱,胶原纤维明显增多,CVF明显升高(P<0.01)。与DM组相比,曲尼司特各剂量组上述变化均有改善,CVF呈现不同程度下降(P<0.01)。与NC组相比,DM组大鼠左室心肌TGF-β1蛋白表达增加(P<0.01)。与DM组相比,曲尼司特各剂量组心肌TGF-β1蛋白表达减少(P<0.01),以曲尼司特高剂量组改善明显(P<0.01)。结论曲尼司特可抑制心肌纤维化,对糖尿病心肌具有保护作用,其保护作用可能与减少糖尿病心肌TGF-β1蛋白表达有关。Objective To observe the effects of tranilast on myocardial fibrosis and expressions of transforming growth factor - β1 in diabetic rats and investigate the protective effect and mechanism of tranilast on cardiac muscle in diabetic rat. Methods Among the forty healthy SD rats, ten were randomly selected as the normal control group （ NC）, and the rest thirty rats were established as diabetesmellitus rat models by tail vein injection of 30 mg · kg^（-1） lstreptozotoin once. The dia- betesmellitus rat models were randomly divided into diabetic model group （DM）, low dose of tranilast （tral） and high dose of tranilast therapy group （tra2）. Each therapy group contained 10 rats. Tranilast of 100, 200 rag/ （kg ~ d） was respective- ly given to the low, high doses of drug therapy groups by garage for 12 weeks. Rats＇ blood glucose and heart quality index （HM1） were calculated. Morphological change was observed and myocardial collagen volume fraction （CVF） was measured by Masson staining and the protein expression level of TGF - β1 was determined by immunohistochemistry. Results Compared with the NC group, the blood glucose and HMI of DM were significantly increased （P 〈0. 01 ）, ± dp/dtmax was significantly reduced （P 〈 0. 01 ）, while compared with the DM, HMI was reduced and ± dp/dtmax was significantly up - regulated （P 〈 0. 05）. The cardiac muscle fibers of DM were in derangement, collagen fibers were increased, and the level of CVF was significantly up - regulated （ P 〈 0. 01 ）. Compared with the DM, HMI and ± dp/dtmax of tranilast treatment groups were improved and CVF showed different degrees of decline （P 〈0.01 ）. Compared with the NC, the protein expression level of TGF - β1 was significantly up - regulated （P 〈 0. 01 ）. Compared with the DM, the protein expression level of TGF - β1 of tranilast treatment groups was reduced （P 〈 0. 01 ）. High dose of tranilast group （tra2） had been improved obviously （P 〈 0. 01 ）. Conclusions

关 键 词：曲尼司特 糖尿病 心肌 转化生长因子-Β1 

分 类 号：R542.2[医药卫生—心血管疾病]