Amelioration of glomerulosclerosis with all-trans retinoic acid is linked to decreased plasminogen activator inhibitor-1 and α-smooth muscle actin  

作　　者：Xia LIU Lei LU Bei-bei TAO Ai-ling ZHOU Yi-chun ZHU 

机构地区：[1]Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai 200032, China [2]Department of Pathophysiology, Nantong University Nantong Medical College, Nantong 226001, China

出　　处：《Acta Pharmacologica Sinica》2011年第1期70-78,共9页中国药理学报（英文版）

基　　金：Acknowledgements This work was supported by grants from the Ministry of Science and Technology of China （No 2010CB912601, 2006CB503804, 2009ZX09303-006, 2009ZX09301-011）, the National Natural Science Foundation of China （No 30825016, 30971064）, the Science and Technology Commission of Shang- hai Municipality （No 09XD1400400, 08JC1401400） and College Natural Science Research Foundation of Jiangsu Province （No 07KJD310171）. We would like to thank Dr Peter ROSE for critical comments regarding this manuscript.

摘　　要：Aim： To examine the effects of all-trans retinoic acid （atRA） on renal morphology and function as well as on renal plasminogen activator inhibitor-1 （PAl-1） expression and plasmin activity in rats with 5/6 nephrectomy. Methods. Adult male Sprague Dawley rats were given 5/6 nephrectomy or sham operation. Renal function was measured 2 weeks later. The nephrectomized rats were assigned to groups matched for proteinuria and treated with vehicle or atRA （5 or 10 mg/kg by gastric gavage once daily） for the next 12 weeks. Rats with sham operation were treated with vehicle. At the end of the treatments, kidneys were collected for histological examination, Western blot analysis, and enzymatic activity measurements. Results： The 5/6 nephrectomy promoted hypertension, renal dysfunction, and glomerulosclerosis. These changes were significantly reduced in the atRA-treated group. The expressions of PAl-1 and （x-smooth muscle actin （（x-SMA） were significantly increased in the vehicle-treated nephrectomized rats. Treatment with atRA significantly reduced the expressions of PAl-1 and （x-SMA. However, plasmin activity remained unchanged following atRA treatment. Conclusion： Treatment with atRA ameliorates glomerulosclerosis and improves renal function in rats with 5/6 nephrectomy. This is associated with a decrease in PAl-1 and α-SMA, but not with a change in plasmin activity.Aim： To examine the effects of all-trans retinoic acid （atRA） on renal morphology and function as well as on renal plasminogen activator inhibitor-1 （PAl-1） expression and plasmin activity in rats with 5/6 nephrectomy. Methods. Adult male Sprague Dawley rats were given 5/6 nephrectomy or sham operation. Renal function was measured 2 weeks later. The nephrectomized rats were assigned to groups matched for proteinuria and treated with vehicle or atRA （5 or 10 mg/kg by gastric gavage once daily） for the next 12 weeks. Rats with sham operation were treated with vehicle. At the end of the treatments, kidneys were collected for histological examination, Western blot analysis, and enzymatic activity measurements. Results： The 5/6 nephrectomy promoted hypertension, renal dysfunction, and glomerulosclerosis. These changes were significantly reduced in the atRA-treated group. The expressions of PAl-1 and （x-smooth muscle actin （（x-SMA） were significantly increased in the vehicle-treated nephrectomized rats. Treatment with atRA significantly reduced the expressions of PAl-1 and （x-SMA. However, plasmin activity remained unchanged following atRA treatment. Conclusion： Treatment with atRA ameliorates glomerulosclerosis and improves renal function in rats with 5/6 nephrectomy. This is associated with a decrease in PAl-1 and α-SMA, but not with a change in plasmin activity.

关 键 词：NEPHRECTOMY plasminogen activator inhibitor 1 PLASMIN RETINOIDS α-smooth muscle actin 

分 类 号：S856.59[农业科学—临床兽医学] Q986[农业科学—兽医学]