Inhibition of FoxO1 exerts a protective effect on diabetic cardiomyopathy rats by regulating JAK/STAT3 signaling pathway
10.3969/j.issn.1006-6187.2024.09.011
- VernacularTitle:抑制叉头框蛋白O1通过调控Janus激酶/信号转导与转录激活子3信号通路对糖尿病心肌病大鼠心肌细胞保护作用的研究
- Author:
Huilin LUO
1
;
Zhilin WU
;
Yunyun YANG
Author Information
1. 430015 武汉市红十字会医院麻醉科
- Keywords:
Forkhead box O1;
Janus kinase/signal transducer and activator of transcription 3 pathway;
Diabetic cardiomyopathy;
Apoptosis
- From:
Chinese Journal of Diabetes
2024;32(9):689-694
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the impact of forkhead box O1(FoxO1)on oxidative stress andcardiomyocyte apoptosis in diabetic cardiomyopathy(DCM)rats through Janus kinase(JAK)/signal transducer and activator of transcription 3(STAT3)pathway.Methods A total of 60 rats were divided into normal control group(NC),model group(Mod),FoxO1 agonist group(Res),FoxO1 inhibitor group(AS1842856)and FoxO1 inhibitor+AG490 group(AS1842856+AG490),with 12 rats in each group.DCM models were established in all groups except NC group.After successful modeling,they were given drugs,and the levels of superoxide dismutase(SOD),malondialdehyde(MDA)and glutathione peroxidase(GSH-PX)were tested.HE and Masson staining were used to detect the pathological damage of myocardial tissue.TUNEL staining was used to observe myocardial apoptosis.Western blot was used to detect FoxO1,Bim,Bcl-2 related X protein(Bax),p-JAK1,p-JAK2,p-STAT3,JAK1,JAK2 and STAT3 proteins.Results Compared with NC group,the expressions of FBG,MDA,cardiomyocyte apoptosis rate,FoxO1 protein,Bax protein and Bim protein were increased(P<0.05),while the expressions of HR,LVEF,LVFS,GSH-PX,SOD,p-JAK1/JAK1,p-JAK2/JAK2 and p-STAT3/STAT3 were increased in Mod group(P<0.05).Compared with Mod group,FBG,MDA,myocardial apoptosis rate,FoxO1 protein,Bax protein and Bim protein increased(P<0.05),while the expressions of HR,LVEF,LVFS,GSH-PX,SOD,p-JAK1/JAK1,p-JAK2/JAK2 and p-STAT3/STAT3 decreased in Res group(P<0.05).The expressions of HR,LVEF,LVFS,GSH-PX,SOD,p-JAK1/JAK1,p-JAK2/JAK2 and p-STAT3/STAT3 increased(P<0.05),while FBG,MDA,myocardial apoptosis rate,FoxO1 protein,Bax protein and Bim protein decreased in AS1842856 group(P<0.05).Compared with AS1842856 group,FBG,MDA,myocardial apoptosis rate,FoxO1 protein,Bax protein and Bim protein increased(P<0.05),and HR,LVEF,LVFS,GSH-PX,SOD,p-JAK1/JAK1,p-JAK2/JAK2,p-STAT3/STAT3 decreasedin AS1842856+AG490 group(P<0.05).Conclusions Inhibition of FoxO1 may exert a protective effect on DCM rats by activating the JAK2/STAT3 pathway.
