洛沙坦对肥胖Zucker大鼠肾组织环氧化酶2表达的影响

Effect of losartan on the cyclooxygenase 2 expression in the obese Zucker rat kidney

目的探讨血管紧张素Ⅱ(AngⅡ)1型受体拮抗剂(ARB)洛沙坦对代谢综合征(MS)肾组织环氧化酶2(COX-2)表达的影响及其机制。方法把7周大的MS模型肥胖Zucker大鼠随机分成洛沙坦处理组和未处理组,以瘦Zucker大鼠为对照组,连续给药4个月后观察肾组织内COX-2的表达。另外,用AngⅡ刺激6 h的系膜细胞和用从微型渗透泵灌注AngⅡ5 d的C57BL/6小鼠肾脏提取的肾皮质,观察COX-2的表达。采用RT-PCR和Western印迹法分别检测COX-2 mRNA和蛋白的表达。结果洛沙坦可阻止肥胖Zucker大鼠肾组织内COX-2表达增加。AngⅡ直接刺激可以诱导系膜细胞和肾组织内COX-2表达增加。结论AngⅡ可以调控MS肾组织内COX-2表达增加。ARB可以通过抑制COX-2的表达保护MS肾脏,这对应用非COX-2抑制剂来保护MS肾脏具有重要的意义。

Objective To investigate the effect of angiotensin Ⅱ （AngⅡ） type 1 receptor blocker losartan on the cyclooxygenase 2 （COX-2） expression in metabolic syndrome （MS）kidney. Methods Seven-week-old male obese Zucker rats, a model of MS, were randomly divided into losartan treated and untreated group, and lean Zucker rats were used as controls. The obese Zucker rats of treated group received losartan for 4 months continuously. COX-2 expression was examined for all rats after 4 months. Ang Ⅱ-stimulated mesangial ceils and cortical tissue from AngⅡ-infused C57BL/6 mouse kidney by osmotic minipumps were used in this study. RNA and protein were obtained from renal cortical tissue or mesangial ceils for RT-PCR and Western blot. Results Compared to the lean controls, obese Zucker rats showed a significant increase of COX-2 expression in the renal cortical tissue and these abnormalities were prevented by administration of losartan. Furthermore, the direct stimulation of Ang Ⅱ increased COX-2 expression in mesangial ceils in vitro and renal cortical tissue in vivo. Conclusions MS-induced COX-2 expression in the kidney is regulated by Ang Ⅱ. Losartan as a non COX-2 inhibitor can protect MS kidney, at least in part, by inhibition of COX-2 activation.