Hypoxia-inducible factor prolyl hydroxylase inhibitor alleviated inflammatory response and prevented renal ischemia-reperfusion injury in mice
10.3760/cma.j.cn421203-20210420-00133
- VernacularTitle:HIF-PHI减轻炎症反应预防小鼠肾缺血再灌注损伤
- Author:
Jie ZHANG
1
;
Xinyue HOU
;
Fumin CHENG
;
Lei LIU
;
Zhigang WANG
;
Jinfeng LI
;
Hongchang XIE
;
Luyu ZHANG
;
Wenjun SHANG
;
Guiwen FENG
Author Information
1. 郑州大学第一附属医院肾移植科 450052
- Keywords:
Ischemia reperfusion injury;
Hypoxia-inducible factor;
Mouse
- From:
Chinese Journal of Organ Transplantation
2021;42(10):610-614
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore whether hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) preconditioning can relieve inflammation, reduce cell apoptosis and alleviate renal ischemia-reperfusion injury in mice.Methods:Male C57BL/6 mice were randomly divided into three groups of sham operation (sham), ischemia reperfusion injury (IRI) and IRI+ HIF-PHI ( n=6 each). In IRI+ HIF-PHI group, mice received an intragastric dose of roxadustat (20 mg/kg) every other day one week before. After renal IRI modeling, serum creatinine (SCr) level was monitored and hematoxylin-eosin (HE) staining employed for observing the pathological changes of renal tissue and scoring injury degree. Apoptosis of renal tubular epithelial cells was assessed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). Reverse transcription-polymerase chain reaction (RT-PCR) was utilized for detecting the mRNA expressions of HIF-1α, TNF-α and IL-1β in renal tissues. Immunofluorescence and immunohistochemistry were employed for detecting the expressions of hypoxia-inducing factor 1α (HIF-1α), inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Results:As compared with IRI group, SCr level declined markedly in IRI+ HIF-PHI group ( P<0.01), renal tissue injury improved markedly, semi-quantitative score of renal tubule injury dropped ( P<0.01), apoptotic cells decreased ( P<0.01) and the expression levels of TNF-α and IL-1β declined ( P<0.05). Compared with sham group, the mRNA expression of HIF-1α was not significantly elevated in IRI group ( P>0.05). Immunofluorescence showed that the expression of HIF-1α in medulla of renal tissues was up-regulated in IRI group, but not markedly in cortex. While the mRNA expression of HIF-1α was markedly up-regulated after a pretreatment of HIF-PHI ( P<0.05), the expression spiked markedly in renal cortex, but was weaker in medulla than that in IRI group. Conclusions:HIF-PHI can boost the expression level of HIF-1α, reduce the expression of inflammatory factors, relieve the inflammatory response, reduce cell apoptosis, improve renal function and alleviate renal ischemia reperfusion injury.
