Spironolactone rescues renal dysfunction in obstructive jaundice rats by upregulating ACE2 expression.

Abstract

Postoperative acute renal failure in patients with obstructive jaundice is still a serious clinically complication, yet the mechanisms remain unclear. Renin-angiotensin-aldosterone system (RAAS) plays a central role in renal disease progression. Several lines of evidence shows that angiotensin-converting-enzyme-2 (ACE2), a main effector of RAAS acts as a local regulator for renal protection. This study aims to investigate the role of ACE2 and the effect of spironolactone treatment in obstructive jaundice(OJ) rats with renal injury. The rats with obstructive jaundice were established by bile duct ligation. Total bilirubin (TBil), serum creatinine (Scr) and the expression of ACE2 in kidney tissue of obstructive jaundice rats were detected. Comparatively, the expression of ACE2, renin, angiotensin II (AngII), angiotensin-(1-7)[Ang-(1-7)], aldosterone and intercellular adhesion molecule 1 (ICAM-1) in kidney tissues after spironolactone administration were measured by ELISA. Renal necrosis, inflammation and fibrosis induced by OJ were also measured by HE staining and Masson staining. The correlation between the expression of ACE2 and TBil, also the Scr level were investigated. With the time of common bile duct ligation prolonged, the TBil and Scr concentration increased while the expression of ACE2 in OJ rats' kidney tissues decreased. However, after spironolactone intervention, the expressions of ACE2, renin, AngII, Ang-(1-7), aldosterone and ICAM-1 in kidney tissue were changed, moreover, necrotic, inflammatory and fibrotic condition was also decreased. The relationship between the mRNA expression of ACE2 and TBil/Scr was observed to be moderately negatively correlated (r = -0.516, R2 = 0.292, P < 0.01), (r = -0.576, R2 = 0.332, P < 0.01), respectively. RAAS exerted an important effect in the renal damage caused by OJ. Spironolactone intervention not only improved the degree of renal fibrosis induced by OJ, but also upregulated the ACE2 expression in the kidney of OJ rats and rescued the renal function.