Artesunate alleviates renal ischemia-reperfusion injury in rats by inhibiting pyroptosis via NLRP3 inflammasome
10.3969/j.issn.1674-7445.2021.06.014
- VernacularTitle:青蒿琥酯通过NLRP3炎症小体抑制细胞焦亡减轻大鼠肾缺血-再灌注损伤
- Author:
Qiang YUAN
1
;
Kaiwen SHEN
;
Ruibo ZHANG
;
Qiang WANG
;
Yuting WU
;
Jun SHEN
Author Information
1. Department of Urology Surgery, the Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
- Publication Type:Research Article
- Keywords:
Artesunate;
Kidney transplantation;
Ischemia-reperfusion injury;
NOD-like receptor protein 3;
Pyroptosis;
Inflammation;
Serum creatinine;
Blood urea nitrogen
- From:
Organ Transplantation
2021;12(6):733-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect and mechanism of artesunate on renal ischemia-reperfusion injury (IRI) in rat. Methods Twenty-five SD rats were randomly divided into the sham operation group (Sham group), model group (IRI group), low-dose artesunate group (ART-L group), high-dose artesunate group (ART-H group) and NLRP3 inflammasome inhibitor group (INF39 group), with 5 rats in each group. The levels of serum creatinine (Scr), blood urea nitrogen (BUN) and pathological damage of renal tissue were analyzed. The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in serum were quantitatively measured. The expression level of IL-1β in renal tissues was determined by immunohistochemical staining. The expression levels of pyroptosis-related proteins were detected by fluorescent staining and Western blot. Results Compared with the Sham group, the levels of Scr and BUN were higher, the renal tissue injury was aggravated, the expression levels of TNF-α, IL-6 and IL-1βwere higher, and the expression levels of kidney injury molecule (KIM-1), pyroptosis-related protein NOD-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase (Caspase-1), Gasdermin D (GSDMD) and IL-1β proteins were higher in the IRI group. Compared with the IRI group, the levels of Scr and BUN were decreased, the renal tissue injury was mitigated, the expression levels of TNF-α, IL-6 and IL-1β were down-regulated, and the expression levels of KIM-1, NLRP3, Caspase-1, GSDMD and IL-1β proteins were down-regulated in the ART-L, ART-H and INF39 groups. Conclusions Artesunate may inhibit pyroptosis induced by NLRP3 inflammasome, down-regulate the expression levels of pyroptosis -related proteins, reduce the release of inflammatory factors after renal IRI and alleviate renal IRI.
