南方医科大学学报2017，Vol.37Issue(4)：505-511,7.DOI:10.3969/j.issn.1673-4254.2017.04.14
厄贝沙坦可减轻2型糖尿病db/db小鼠心肌组织的炎症反应
Irbesartan ameliorates cardiac inflammation in type 2 diabetic db/db mice
摘要
Abstract
Objective To investigate the protective effects of irbesartan against cardiac inflammation associated with diabetes and obesity in the db/db mouse model of type 2 diabetes and explore the underlying mechanisms. Methods Twenty- four 10-week-old diabetic db/db mice were equally randomized into irbesartan treatment (50 mg/kg per day) group and model group, using 12 nondiabetic littermates (db/+) as the controls, The mice were treated with irbesartan or saline vehicle for 16 consecutive weeks, after which the heart pathology was observed and the heart weight, body weight, and serum levels of fasting blood glucose (FBG), total cholesterol(TC), and triglycerides(TG) were measured. The expression of nuclear factor-kappaB (NF-κB) p65 in the myocardium was assessed with immunohistochemistry, the protein levels of P-IкBα ,IкBαandβ-actin were analyzed with Western blotting, and the pro-inflammatory cytokines IL-6 and TNF-αmRNA were detected using quantitative real-time PCR (qPCR). Results Compared with db/+mice, the saline-treated db/db mice developed obesity, hyperglycemia and hyperlipidemia (P<0.01). Histopathological examination of the heart tissue revealed inflammatory cell infiltration, increased myocardial interstitium and disorders of myocardial fiber arrangement. The diabetic mice showed increased P-IкBα and decreased IκBα protein levels, enhanced activity and expression of NF-κB in the hearts, and increased mRNA expression of IL-6 and TNF-αin the myocardium. These abnormalities were all associated with increased inflammatory response. Treatment with irbesartan improved the heart architecture and attenuated high glucose-induced inflammation in the diabetic mice. Conclusion Treatment with irbesartan attenuates cardiac inflammation in type 2 diabetic db/db mice, and this effect was probably associated with the suppression of cardiac angiotensin Ⅱ and NF-κB signaling pathway.关键词
厄贝沙坦/糖尿病心肌病/NF-кB/炎症Key words
irbesartan/diabetic cardiomyopathy/nuclear factor-κB/inflammation引用本文复制引用
叶显朗,黄伟昌,郑彦涛,梁莺,龚望球,杨翀邈,刘斌..厄贝沙坦可减轻2型糖尿病db/db小鼠心肌组织的炎症反应[J].南方医科大学学报,2017,37(4):505-511,7.基金项目
广东省科技计划项目(2015A020212021) （2015A020212021）
