Roxadustat improves myocardial ischemia-reperfusion injury in mice by inhibiting apoptosis and inflammatory response
- VernacularTitle:罗沙司他通过抑制凋亡和炎症反应改善小鼠心肌缺血再灌注损伤
- Author:
Dengta CAI
1
;
Jingyi CHANG
;
Shanshan JIA
;
Yinqiong TU
Author Information
- Keywords: myocardial reperfusion injury; apoptosis; inflammation; Roxadustat
- From: Tianjin Medical Journal 2024;52(11):1146-1151
- CountryChina
- Language:Chinese
- Abstract: Objective To investigate the improvement effect and related mechanism of roxadustat on myocardial ischemia-reperfusion(I/R)injury in mice.Methods Twenty four male C57BL/6N mice were randomly divided into the sham operation group,the control group and the roxadustat group,with eight mice in each group.A mouse myocardial I/R model was established.The control group was given 100 μL saline injection containing 5%dimethyl sulfoxide by gavage.The roxadustat group was given 25 mg/kg roxadustat by gavage.The left anterior descending coronary artery of mice in both groups was ligated for 40 minutes,and then reperfusion for 24 hours to establish the myocardial I/R model.In the sham operation group,only the left anterior coronary artery was pierced without ligation.The area of myocardial infarction in mice was detected by triphenyltetrazolium chloride(TTC)staining.The apoptosis of mouse cardiomyocytes was detected by TdT-mediated dUTP nick and labeling(TUNEL)staining.The expression of apoptosis-related proteins bcl-2 associated X protein(Bax),Caspase3 and inflammatory cell markers F4/80 and myeloperoxidase(MPO)were detected by immunohistochemistry staining.The damage of myocardial cells was observed by hematoxylin-eosin(HE)staining.Results The area of myocardial infarction after myocardial I/R was reduced in the roxadustat group compared to the control group and the sham operation group(P＜0.05).The number of apoptotic cells was higher in the control group and the roxadustat group than that in the sham operation group,and the number of apoptotic cells was lower in the roxadustat group than that in the control group(P＜0.05).The expression levels of Bax and Caspase3 proteins in myocardial tissue were higher in the control group and the roxadustat group than those in the sham operation group,while those of the roxadustat group was lower than those of the control group(P＜0.05).The expression levels of F4/80 and MPO proteins in myocardial tissue were lower in the roxadustat group than those in the control group(P＜0.05).In the control group,the myocardial tissue arrangement was disordered,and there was an increase in interstitial vacuoles.Compared with the control group,the myocardial cells were arranged more neatly in the roxadustat group,and the interstitial vacuoles were reduced.Conclusion Roxadustat can reduce the myocardial infarction area after I/R injury,inhibit myocardial cell apoptosis,alleviate myocardial injury,reduce infiltration of myocardial macrophages and neutrophils,and reduce inflammatory injury.
