Telmisartan protects against insulin resistance by attenuating inflammatory response in rats
Telmisartan protects against insulin resistance by attenuating inflammatory response in rats
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DOI：
10.1007/s11596-011-0374-7
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发表时间：
2011-06
期刊：
影响因子：
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通讯作者：
Xizhen Xu;Xiaoming Yin;W. Feng;Geng Li;Daowen Wang;L. Tu
中科院分区：
文献类型：
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作者：
Xizhen Xu;Xiaoming Yin;W. Feng;Geng Li;Daowen Wang;L. Tu
本研究探讨了替米沙坦对高脂饮食大鼠胰岛素抵抗的影响及其可能机制。将40只雄性SD大鼠随机分为4组：ND组（n=10）和HD组（n=10），适应1周后给予普通饲料或高脂饲料20周; ND+替米沙坦组（n=10）和HD+替米沙坦组（n=10），其中大鼠的初始给药方式与ND或HD组相同，然后再经口灌胃给予替米沙坦（每日5 mg/kg）5周。ELISA法检测相关炎症因子。Western blotting检测脂肪和肝脏中单核细胞趋化蛋白1（MCP-1）、磷酸化JNK和IκB-α的表达。RT-PCR法检测脂肪和肝脏中CRP和血管紧张素II受体1（AT 1）mRNA的表达。结果显示，替米沙坦体内给药逆转了胰岛素抵抗，表现为空腹血糖水平、空腹胰岛素水平和胰岛素抵抗评估稳态模型（HOMA-IR）降低。此外，替米沙坦给药可显著降低血清CRP、TNF-α和IL-1β水平，升高血清IL-10水平。高脂饮食诱导的脂肪和肝脏中CRP mRNA、AT 1 mRNA和MCP-1的升高以及IκB-α的降低也受到抑制。结论：替米沙坦体内给药可能通过减弱炎症反应途径改善胰岛素抵抗。
This study investigated the effects of telmisartan on insulin resistance in high-fat diet-treated rats and the possible mechanism. A total of 40 male Sprague-Dawley rats enrolled in the study were divided into 4 groups at random: ND group (n=10) and HD group (n=10), in which the rats were given a normal chow diet or a high-fat diet for 20 weeks following a one-week adaptation; ND+telmisartan (n=10) group and HD+telmisartan group (n=10), in which the rats were initially administered in the same way as the ND or HD group, and then they were orally gavaged with telmisartan (5 mg/kg daily) additionally for 5 weeks. Related inflammatory factors were measured by ELISA. Monocyte chemotactic protein 1 (MCP-1), phosphorylated JNK and IκB-α expressions in both adipose and liver were detected by Western blotting. CRP and angiotensin II receptor 1 (AT1) mRNA expressions in both adipose and liver were determined by RT-PCR. The results showed that telmisartan administrationin vivoreversed insulin resistance as evidenced by a decrease in plasma fasting glucose levels, plasma fasting insulin levels and homeostasis model of assessment-insulin resistance (HOMA-IR). Furthermore, telmisartan administration significantly reduced serum CRP, TNF-α and IL-1β levels, and elevated serum IL-10 levels. It was also found to hamper the high-fat diet-induced increase in CRP mRNA, AT1 mRNA and MCP-1, and decrease in IκB-α in both adipose and liver. It was concluded that telmisartan administrationin vivomay improve insulin resistance through attenuated inflammatory response pathways.