Angiotensin-(1-7) reduces proteinuria and diminishes structural damage in renal tissue of stroke-prone spontaneously hypertensive rats
Angiotensin-(1-7) reduces proteinuria and diminishes structural damage in renal tissue of stroke-prone spontaneously hypertensive rats
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DOI：
10.1152/ajprenal.00278.2010
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发表时间：
2011-01-01
影响因子：
4.2
通讯作者：
Dominici, Fernando P.
中科院分区：
文献类型：
--
作者：
Giani, Jorge F.;Munoz, Marina C.;Dominici, Fernando P.
首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容血管紧张素-(1-7)可减少卒中易患自发性高血压大鼠的蛋白尿，减轻肾组织结构损伤。Am J Physiol Renal Physiol 300：F272-F282,2011。2010年10月20日首次出版；DOI：10.1152/ajprenal.00278.2010。-血管紧张素(Ang)-(1-7)是肾素-血管紧张素-醛固酮系统的重要功能终产物，该系统作用于平衡Ang II的生理活动。在肾脏，Ang-(1-7)通过抑制促生长途径和减少蛋白尿发挥有益的作用。我们检查了每日给予血管紧张素-(1-7)(0.6 mg·kg(-1))治疗2周是否有效。(-1天)对盐负荷性卒中易感型自发性高血压大鼠(SHRSP)具有肾脏保护作用。治疗前后分别测定体重、血糖、甘油三酯、胆固醇、血浆Na+、K+水平。此外，还评估了动脉血压、蛋白尿和肌酐清除量的每周变化。用Masson‘s三色染色法测定肾纤维化程度。免疫组织化学方法检测白细胞介素6(IL-6)、肿瘤坏死因子(TNF)-α和核因子-kappaB(NF-kappa B)的表达，Western blotting分析结果证实。免疫荧光法检测肾小球内肾上腺素水平。慢性应用Ang-(1-7)可使SHRSP的动脉压恢复正常，降低血糖和甘油三酯血症，改善蛋白尿，并改善肾脏的结构变化，免疫荧光检测显示肾小球内肾上腺素水平恢复。这些结果伴随着IL-6、肿瘤坏死因子-α和核因子-kappaB的免疫染色和丰度的降低。在这种情况下，目前的研究为Ang-(1-7)在肾脏中的保护作用提供了强有力的证据。
Giani JF, Munoz MC, Pons RA, Cao G, Toblli JE, Turyn D, Dominici FP. Angiotensin-(1-7) reduces proteinuria and diminishes structural damage in renal tissue of stroke-prone spontaneously hypertensive rats. Am J Physiol Renal Physiol 300: F272-F282, 2011. First published October 20, 2010; doi: 10.1152/ajprenal.00278.2010.-Angiotensin (ANG)-(1-7) constitutes an important functional end-product of the renin-angiotensin-aldosterone system that acts to balance the physiological actions of ANG II. In the kidney, ANG-(1-7) exerts beneficial effects by inhibiting growth-promoting pathways and reducing proteinuria. We examined whether a 2-wk treatment with a daily dose of ANG-(1-7) (0.6 mg.kg(-1) . day(-1)) exerts renoprotective effects in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Body weight, glycemia, triglyceridemia, cholesterolemia, as well as plasma levels of Na+ and K+ were determined both at the beginning and at the end of the treatment. Also, the weekly evolution of arterial blood pressure, proteinuria, and creatinine clearance was evaluated. Renal fibrosis was determined by Masson's trichrome staining. Interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and nuclear factor-kappa B (NF-kappa B) levels were determined by immunohistochemistry and confirmed by Western blotting analysis. The levels of glomerular nephrin were assessed by immunofluorescence. Chronic administration of ANG-(1-7) normalized arterial pressure, reduced glycemia and triglyceridemia, improved proteinuria, and ameliorated structural alterations in the kidney of SHRSP as shown by a restoration of glomerular nephrin levels as detected by immunofluorescence. These results were accompanied with a decrease in both the immunostaining and abundance of IL-6, TNF-alpha, and NF-kappa B. In this context, the current study provides strong evidence for a protective role of ANG-(1-7) in the kidney.