Involvement of serine proteases in aldosterone-induced renal injury.

最近有报道称，醛固酮对许多器官都有有害影响，不受其血流动力学影响的影响。然而，这些作用的机制还不是很清楚。我们曾经报道过，合成的丝氨酸蛋白酶抑制剂甲磺酸卡莫司坦可以降低Dah1盐敏感大鼠的血压升高和减轻肾脏损伤。因此，丝氨酸蛋白酶很可能参与了盐敏感型高血压和器官损伤的发病机制。在本研究中，为了阐明丝氨酸蛋白酶在醛固酮和盐诱导的大鼠肾脏损伤中的作用，我们对醛固酮/盐处理的单肾切除大鼠给予坎莫司坦。在卡莫司坦改善大鼠肾小球硬化和肾小管间质纤维化的过程中，我们搜索并检测到一种由醛固酮/盐诱导的丝氨酸蛋白酶。我们的结果表明，丝氨酸蛋白酶与醛固酮/盐引起的肾损伤密切相关，丝氨酸蛋白酶抑制剂可能成为治疗醛固酮相关性肾损伤的一种新策略。

Aldosterone has been recently reported to have harmful effects on many organs independent of its hemodynamic effect. However the mechanisms of these effects have not been well understood.We once reported that the administration of a synthetic serine protease inhibitor camostat mesilate lowered the elevated blood pressure and attenuated kidney injury in Dah1 salt-sensitive rats. So it would be highly probable that serine proteases are involved in the pathogenesis of salt-sensitive hypertension and organ damages. In this study, in order to elucidate the role of serine proteases in the kidney injury induced by aldosterone and salt, we administrated camostat to aldosterone/salt-treated uninephrectomized rats. As camostat ameliorated glomeruloscrelosis and tublointerstitial fibrosis in these rats, we searched and detected one serine protease which was induced by aldosterone/salt. Our results suggest that a serine protease is highly related to kidney injury induced by aldosterone/salt, and serine protease inhibitor could be a new strategy for the treatment of kidney injury associated with aldosterone in human.