Department of Endocrinology, Second Hospital, Shanxi Medical University, 382 Wuyi Road, Taiyuan, Shanxi, P.R. China.
Cardiovasc Diabetol. 2012 Aug 8;11:94. doi: 10.1186/1475-2840-11-94.
Diabetic cardiovascular disease is associated with decreased adiponectin and increased oxidative stress. This study investigated the effect of telmisartan on the expression of adiponectin receptor 2 (adipoR2) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits in the heart and the expression of adiponectin receptor 1 (adipoR1) in aorta in type 2 diabetic rats.
Type 2 diabetes was induced by high-fat and high-sugar diet and intraperitoneal injection of a low dose of streptozotocin (STZ). Heart function, adipoR2, p22phox, NOX4, glucose transporter 4(GLUT4), monocyte chemoattractant protein-1(MCP-1) and connective tissue growth factor (CTGF)in the heart, and adipoR1, MCP-1 and nuclear factor kappa B (NF-κB) in aorta were analyzed in controls and diabetic rats treated with or without telmisartan (5mg/kg/d) by gavage for 12 weeks.
Heart function, plasma and myocardial adiponectin levels, the expression of myocardial adipoR2 and GLUT4 were significantly decreased in diabetic rats (P <0.05). The expression of myocardial p22phox, NOX4, MCP-1, and CTGF was significantly increased in diabetic rats (P <0.05). The expression of adipoR1 was decreased and the expression of MCP-1 and NF-κB was increased in the abdominal aorta in diabetic rats (P <0.05). Telmisartan treatment significantly attenuated these changes in diabetic rats (P <0.05).
Our results suggest that telmisartan upregulates the expression of myocardial adiponectin, its receptor 2 and GLUT4. Simultaneously, it downregulates the expression of myocardial p22phox, NOX4, MCP-1, and CTGF, contributing so to the improvement of heart function in diabetic rats. Telmisartan also induces a protective role on the vascular system by upregulating the expression of adipoR1 and downregulating the expression of MCP-1 and NF-κB in the abdominal aorta in diabetic rats.
糖尿病心血管疾病与脂联素减少和氧化应激增加有关。本研究探讨了替米沙坦对 2 型糖尿病大鼠心脏中脂联素受体 2（adipoR2）和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶亚基的表达以及主动脉中脂联素受体 1（adipoR1）表达的影响。
通过高脂肪高糖饮食和低剂量链脲佐菌素（STZ）腹腔注射诱导 2 型糖尿病。通过灌胃 12 周，分析对照组和糖尿病大鼠心脏功能、adipoR2、p22phox、NOX4、葡萄糖转运蛋白 4（GLUT4）、单核细胞趋化蛋白 1（MCP-1）和结缔组织生长因子（CTGF）以及主动脉中 adipoR1、MCP-1 和核因子 kappa B（NF-κB）的表达，并用替米沙坦（5mg/kg/d）治疗。
糖尿病大鼠心脏功能、血浆和心肌脂联素水平、心肌 adipoR2 和 GLUT4 表达明显降低（P<0.05）。糖尿病大鼠心肌 p22phox、NOX4、MCP-1 和 CTGF 表达明显增加（P<0.05）。糖尿病大鼠主动脉中 adipoR1 表达减少，MCP-1 和 NF-κB 表达增加（P<0.05）。替米沙坦治疗可显著减轻糖尿病大鼠的这些变化（P<0.05）。
我们的结果表明，替米沙坦上调心肌脂联素、其受体 2 和 GLUT4 的表达。同时，它下调心肌 p22phox、NOX4、MCP-1 和 CTGF 的表达，从而改善糖尿病大鼠的心脏功能。替米沙坦还通过上调糖尿病大鼠主动脉中 adipoR1 的表达和下调 MCP-1 和 NF-κB 的表达，对血管系统发挥保护作用。
