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

  • Er-liang Kong
  • Jin-min Zhang
  • Ni An
  • Yong Tao
  • Wei-feng YuEmail author
  • Fei-xiang WuEmail author
Research Article
  • 132 Downloads

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.

Keywords

Obstructive jaundice (OJ) Renal function Angiotensin-converting-enzyme-2 (ACE2) Renin-angiotensin-aldosterone system (RAAS) Spironolactone 

Abbreviations

OJ

Obstructive jaundice

RAAS

Renin-angiotensin-aldosterone system

TBil

Total bilirubin

Scr

Serum creatinine

ACE2

Angiotensin-converting-enzyme-2

AngII

Angiotensin II

[Ang-(1–7)]

Angiotensin-(1–7)

ICAM-1

Intercellular adhesion molecule 1

RAS

Renin angiotensin system

SO group

Sham-operated group

BDL group

Bile duct ligation group

HE

Hematoxylin and eosin

BDL + S group

Bile duct ligation with spironolactone treatment group

Notes

Acknowledgements

The results presented in this paper have not been published previously in whole or part.

Authors’ contributions

EK and NA performed the experiments and analyzed the data; EK, NA, JZ, YT, XM, WY and FW conceived and designed the experiments; WY and FW analyzed the data and EK, NA and JZ contributed the writing of the manuscript. EK and NA contributed equally to this work. All authors read and approved the final manuscript.

Compliance with ethical standards

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Copyright information

© The International CCN Society 2018

Authors and Affiliations

  1. 1.Department of Anesthesiology & Intensive Care, Shanghai Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghaiChina

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