Role of Sirolimus in renal tubular apoptosis in response to unilateral ureteral obstruction
Authors: Yan-Jie Zhang
Yan Zhang
Sao-Ling Zheng
Wei-Wei Wang
Peng Xia
Hai-Ping Zhu
Yang-Yang Zhuang
Bi-Cheng Chen
Yi-Rrong Yang
Mei Yang
Journal: International Journal of Medical Sciences (2018)
Discipline: CLINICAL MEDICINE
Keywords: Urinary tract obstruction; apoptosis; proliferation; renoprotection; sirolimus.
Affiliations: Department of Intensive Care Unit, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China 325015., Transplantation centre, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China 325015., Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325015, China.

Abstract:  Renal tubule cell apoptosis plays a pivotal role in the progression of chronic renal diseases. The previous study indicates that Sirolimus is effective on unilateral ureteral obstruction (UUO)-induced renal fibrosis. However, the role of Sirolimus in renal tubular apoptosis induced by UUO has not yet been addressed. The aim of this study was to determine the role of Sirolimus in renal tubular apoptosis induced by UUO. Male Sprague-Dawley rats were divided into three groups, sham-operated rats, and after which unilateral ureteral obstruction (UUO) was performed: non-treated and sirolimus-treated (1mg/kg). After 4, 7 and 14 d, animals were sacrificed and blood, kidney tissue samples were collected for analyses. Histologic changes and interstitial collagen were determined microscopically following HE and Masson's trichrome staining. The expression of PCNA was investigated using immunohistochemistry and the expression of Bcl-2, Bax, caspase-9, and caspase-3 were investigated using Western blot in each group. Tubular apoptotic cell deaths were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Sirolimus administration resulted in a significant reduction in tubulointerstitial fibrosis scores. After UUO, there was an increase in tubular and interstitial apoptosis in untreated controls as compared to Sirolimus treatment rats (P&lt;0.05). In addition, the expression of PCNA, Bcl-2, Bax, caspase-9, and caspase-3 in obstructed kidney was characterized by immunohistochemistry and Western blot analyses demonstrating that sirolimus treatment significantly reduced PCNA, Bax, caspase-9 and cleaved caspase-3 expression compared to those observed in controls (P&lt;0.05), whereas, Bcl-2 in the obstructed kidney were decreased in untreated controls compared to Sirolimus treatment rats subjected to the same time course of obstruction (P&lt;0.05). We demonstrated a marked renoprotective effect of sirolimus by inhibition of UUO-induced renal tubular apoptosis in vivo. 

Retracted: No

PubPeer comments:
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