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厄贝沙坦通过激活过氧化物酶体增殖物激活受体 γ 预防大鼠代谢综合征。

Irbesartan prevents metabolic syndrome in rats via activation of peroxisome proliferator-activated receptor γ.

机构信息

Department of Pharmacology, Osaka Medical College, Takatsuki, Osaka, Japan.

出版信息

J Pharmacol Sci. 2011;116(3):309-15. doi: 10.1254/jphs.11053fp. Epub 2011 Jun 18.

Abstract

Irbesartan, an angiotensin-receptor blocker, is a known agonist of peroxisome proliferator-activated receptor (PPAR) γ. In this study, thirteen-week-old spontaneously hypertensive (SHR)/NDmcr-cp rats, representing a genetic model of metabolic syndrome, were treated daily with placebo, irbesartan (30 mg/kg), valsartan (10 mg/kg), or pioglitazone (10 mg/kg) for 4 weeks. Significant reductions in systolic blood pressure were seen in the irbesartan- and valsartan-treated groups, but not in the pioglitazone-treated group. Compared with the placebo group, plasma insulin, homeostasis model assessment of insulin resistance index, and plasma triglyceride levels were significantly lower while plasma adiponectin levels were significantly higher in the pioglitazone- and irbesartan-treated groups, but not in the valsartan-treated group. Significant increases in the gene expression of adiponectin and GLUT4 within adipose tissue were also observed in the pioglitazone- and irbesartan-treated groups, but not in the valsartan-treated group. These findings suggest that through PPARγ stimulation along with angiotensin II inhibition, irbesartan may be an optimal treatment option in the prevention of metabolic syndrome as well as hypertension.

摘要

厄贝沙坦是一种血管紧张素受体阻滞剂,已知是过氧化物酶体增殖物激活受体 (PPAR)γ 的激动剂。在这项研究中,十三周龄的自发性高血压(SHR)/NDmcr-cp 大鼠,代表代谢综合征的遗传模型,每天用安慰剂、厄贝沙坦(30mg/kg)、缬沙坦(10mg/kg)或吡格列酮(10mg/kg)治疗 4 周。厄贝沙坦和缬沙坦治疗组的收缩压显著降低,但吡格列酮治疗组没有。与安慰剂组相比,吡格列酮和厄贝沙坦治疗组的血浆胰岛素、胰岛素抵抗评估的稳态模型指数和血浆三酰甘油水平显著降低,而血浆脂联素水平显著升高,但缬沙坦治疗组没有。吡格列酮和厄贝沙坦治疗组的脂肪组织中脂联素和 GLUT4 的基因表达也显著增加,但缬沙坦治疗组没有。这些发现表明,通过刺激 PPARγ 以及抑制血管紧张素 II,厄贝沙坦可能是预防代谢综合征和高血压的最佳治疗选择。

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