Division of Nephrology, Huashan Hospital and Institute of Nephrology, Fudan University, Shanghai, China.
Nephrology (Carlton). 2013 Dec;18(12):761-9. doi: 10.1111/nep.12146.
Angiotensin-(1-7) (Ang-(1-7)) opposes angiotensin-II-induced cell growth, matrix accumulation and fibrosis in cardiac tissue. However, the role of Ang-(1-7) in the pathogenesis of renal fibrosis is uncertain. This study observed the effects of Ang-(1-7), on its own or in combination with losartan, an angiotensin-receptor blocker, on five-sixths nephrectomized rats.
Male Sprague-Dawley rats underwent five-sixths nephrectomy, and then were either untreated, treated with Ang-(1-7), treated with losartan, or treated with a combination therapy of Ang-(1-7) and losartan. After 8 weeks, renal function was assessed by measuring systolic blood pressure, serum creatinine and proteinuria. The effect of nephrectomy on the renin-angiotensin system was examined by measuring plasma levels of Ang-II and Ang-(1-7). The extent of glomerulosclerosis and tubulointerstitial fibrosis was assessed by periodic acid-Schiff staining and Masson-trichrome staining. The expression of plasminogen activator inhibitor-1, fibronectin and angiopoietins-Tie-2 was investigated by immunohistochemistry and western blot.
In the groups of treated rats, serum creatinine, proteinuria and markers of glomerulosclerosis, such as fibronectin and plasminogen activator inhibitor-1, were ameliorated compared with the untreated, nephrectomized rats. Plasma Ang-(1-7) levels were elevated in all treatment groups, but the plasma Ang-II levels were reduced in the Ang-(1-7)-treated group and the combination therapy group. The ratio of Ang-1/Ang-2 was increased in the combination therapy group compared with two other treatment groups.
Ang-(1-7) ameliorated the renal injury of nephrectomized rats. The combination of Ang-(1-7) treatment alongside losartan exerted a superior effect to that of Ang-(1-7) alone on regression of glomerulosclerosis.
血管紧张素-(1-7)[Ang-(1-7)]拮抗血管紧张素-II 诱导的心肌组织细胞生长、基质积累和纤维化。然而，Ang-(1-7)在肾纤维化发病机制中的作用尚不确定。本研究观察了 Ang-(1-7)、单独使用或与血管紧张素受体阻滞剂氯沙坦联合使用对 6/5 肾切除大鼠的作用。
雄性 Sprague-Dawley 大鼠行 6/5 肾切除，然后不治疗、给予 Ang-(1-7)、给予氯沙坦或给予 Ang-(1-7)和氯沙坦联合治疗。8 周后，通过测量收缩压、血清肌酐和蛋白尿来评估肾功能。通过测量血浆血管紧张素-II 和 Ang-(1-7)水平来检测肾切除对肾素-血管紧张素系统的影响。通过过碘酸希夫染色和 Masson 三色染色评估肾小球硬化和肾小管间质纤维化的程度。通过免疫组化和 Western blot 检测纤溶酶原激活物抑制剂-1、纤维连接蛋白和血管生成素-Tie-2 的表达。
与未治疗、肾切除的大鼠相比，治疗组大鼠的血清肌酐、蛋白尿和肾小球硬化标志物（如纤维连接蛋白和纤溶酶原激活物抑制剂-1）均有所改善。所有治疗组的血浆 Ang-(1-7)水平升高，但 Ang-(1-7)治疗组和联合治疗组的血浆 Ang-II 水平降低。与另外两组相比，联合治疗组的 Ang-1/Ang-2 比值升高。
Ang-(1-7)改善了肾切除大鼠的肾损伤。Ang-(1-7)联合氯沙坦治疗对肾小球硬化的消退作用优于单独使用 Ang-(1-7)。
