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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 losartan on the expression of cyclooxygenase 2 (COX-2) in renal tissue of metabolic syndrome (MS) induced by angiotensin Ⅱ type 1 receptor antagonist (ARB) and its mechanism. Methods The 7-week-old MS model obese Zucker rats were randomly divided into losartan group and untreated group. The lean Zucker rats were used as the control group, and the expression of COX-2 in renal tissues was observed after 4 months continuous administration. In addition, the mesangial cells stimulated with Ang Ⅱ for 6 h and the renal cortex extracted from the kidneys of C57BL / 6 mice infused with Ang Ⅱ 5 d microinvasive pump were used to observe the expression of COX-2. The expression of COX-2 mRNA and protein were detected by RT-PCR and Western blot respectively. Losartan prevented the increase of COX-2 expression in the kidney of obese Zucker rats. Ang Ⅱ direct stimulation can induce the increase of COX-2 expression in mesangial cells and renal tissues. Conclusion Ang Ⅱ can regulate the expression of COX-2 in MS renal tissue. ARB can protect MS kidney by inhibiting the expression of COX-2, which is of great significance for the protection of MS kidney with non-COX-2 inhibitors.