Junaid A, Rosenberg M E, Hostetter T H
University of Manitoba, Winnipeg, Canada.
J Am Soc Nephrol. 1997 Nov;8(11):1732-8. doi: 10.1681/ASN.V8111732.
An interaction between angiotensin (Ang) II and transforming growth factor (TGF)-beta 1 is gaining increasing recognition. Ang II has been implicated in the progression of renal disease, and TGF-beta 1 is a potent fibrosis-promoting cytokine. We sought to determine whether the beneficial effects of renin-angiotensin system blockade on remnant kidney function were associated with a reduction in renal TGF-beta 1 in this model of chronic renal failure. After subtotal renal ablation, rats fed a 40% protein diet and treated with losartan not only had a reduction in systolic BP (96 +/- 8 versus 130 +/- 8 mmHg, P < 0.05, losartan versus control) and urinary protein excretion (4 +/- 5 versus 23 +/- 20 g/d, P < 0.05, losartan versus control), but also exhibited a reduction in renal TGF-beta 1 mRNA (194 +/- 64 versus 411 +/- 101 optical density units, P < 0.05, losartan versus control) and TGF-beta 1 protein levels (9.8 +/- 2.5 versus 18.6 +/- 5.8 ng/g of renal tissue, P < 0.05, losartan versus control). The elevation of TGF-beta 1 in the remnant kidney was most pronounced in the scar region (22.9 +/- 13.1 versus 5.8 +/- 3.7 ng/g, P < 0.05, scar versus nonscar). A combination of reserpine, hydralazine, and hydrochlorothiazide, although effective in lowering systemic BP in this model of chronic renal failure, was not associated with a reduction in proteinuria or TGF-beta 1. We conclude that in this model of progressive renal injury, Ang II antagonism may exert a beneficial effect in part by its negative influence on TGF-beta 1.
血管紧张素（Ang）II与转化生长因子（TGF）-β1之间的相互作用日益受到关注。Ang II与肾脏疾病的进展有关，而TGF-β1是一种强效的促纤维化细胞因子。我们试图确定在这种慢性肾衰竭模型中，肾素-血管紧张素系统阻断对残余肾功能的有益作用是否与肾脏TGF-β1的减少有关。在进行肾次全切除术后，喂食40%蛋白质饮食并用氯沙坦治疗的大鼠不仅收缩压降低（氯沙坦组96±8 mmHg，对照组130±8 mmHg，P<0.05，氯沙坦组与对照组相比）和尿蛋白排泄减少（氯沙坦组4±5 g/d，对照组23±20 g/d，P<0.05，氯沙坦组与对照组相比），而且肾脏TGF-β1 mRNA水平降低（氯沙坦组194±64光密度单位，对照组411±101光密度单位，P<0.05，氯沙坦组与对照组相比）以及TGF-β1蛋白水平降低（氯沙坦组9.8±2.5 ng/g肾组织，对照组18.6±5.8 ng/g肾组织，P<0.05，氯沙坦组与对照组相比）。残余肾脏中TGF-β1的升高在瘢痕区域最为明显（瘢痕区域22.9±13.1 ng/g，非瘢痕区域5.8±3.7 ng/g，P<0.05，瘢痕区域与非瘢痕区域相比）。利血平、肼屈嗪和氢氯噻嗪联合使用，虽然在这种慢性肾衰竭模型中能有效降低全身血压，但与蛋白尿或TGF-β1的减少无关。我们得出结论，在这种进行性肾损伤模型中，Ang II拮抗作用可能部分通过其对TGF-β1的负面影响发挥有益作用。
