Losartan accelerates the repair process of renal fibrosis in UUO mouse after the surgical recanalization by upregulating the expression of Tregs

Int Urol Nephrol. 2019 Nov;51(11):2073-2081. doi: 10.1007/s11255-019-02253-8. Epub 2019 Aug 10.

Abstract

Obstructive nephropathy is a common cause for chronic kidney disease. Surgery, which is adopted to promptly relieve the obstruction, is the most important method to save damaged kidneys. However, earlier studies have shown that renal function will continue to deteriorate until the terminal stage after the obstruction' relief. The aim of this study is to explore the renal fibrosis and investigate the effect of losartan on renal fibrosis after the obstruction' relief using an improved mouse model of relief for unilateral ureteral obstruction (RUUO). Experiments carried out using C57BL/6 mice (n = 30) were randomly divided into RUUO + Losartan group, RUUO group and sham group. Using an improved mouse RUUO model, this study revealed that the mouse kidney for 3- or 7-day unilateral ureteral obstruction undergoing the RUUO surgery was still in a state of injury and fibrosis, while losartan could effectively ameliorate renal fibrosis by upregulating the expression of CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) in kidney after the surgery of RUUO.

Keywords: Losartan; Mouse model; RUUO; Renal fibrosis; Tregs.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Animals
  • Fibrosis / drug therapy
  • Kidney / pathology*
  • Losartan / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Random Allocation
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / physiology*
  • Time Factors
  • Treatment Outcome
  • Up-Regulation / drug effects*
  • Ureteral Obstruction / complications
  • Ureteral Obstruction / surgery

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Losartan