全反式维甲酸改善肾小球硬化与纤溶酶原激活物抑制剂-1 和 α-平滑肌肌动蛋白减少有关。
Amelioration of glomerulosclerosis with all-trans retinoic acid is linked to decreased plasminogen activator inhibitor-1 and α-smooth muscle actin.
机构信息
Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai 200032, China.
出版信息
Acta Pharmacol Sin. 2011 Jan;32(1):70-8. doi: 10.1038/aps.2010.200.
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 (PAI-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 PAI-1 and α-smooth muscle actin (α-SMA) were significantly increased in the vehicle-treated nephrectomized rats. Treatment with atRA significantly reduced the expressions of PAI-1 and α-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 PAI-1 and α-SMA, but not with a change in plasmin activity.
目的
观察全反式维甲酸（atRA）对 5/6 肾切除大鼠肾脏形态和功能以及肾组织纤溶酶原激活物抑制剂-1（PAI-1）表达和纤溶酶活性的影响。
方法
成年雄性 Sprague Dawley 大鼠行 5/6 肾切除或假手术。2 周后检测肾功能。将肾切除大鼠按蛋白尿匹配分组，分别给予 vehicle 或 atRA（5 或 10mg/kg 灌胃，每日 1 次）治疗 12 周。假手术大鼠给予 vehicle 处理。治疗结束时收集肾脏进行组织学检查、Western blot 分析和酶活性测定。
结果
5/6 肾切除导致大鼠发生高血压、肾功能不全和肾小球硬化。atRA 治疗组这些变化明显减轻。vehicle 处理的肾切除大鼠 PAI-1 和α-平滑肌肌动蛋白（α-SMA）表达明显增加。atRA 治疗显著降低了 PAI-1 和α-SMA 的表达。然而，atRA 治疗后纤溶酶活性没有变化。
结论
atRA 治疗可改善 5/6 肾切除大鼠的肾小球硬化和肾功能，这与 PAI-1 和α-SMA 减少有关，而与纤溶酶活性无关。
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