Treadmill exercise improves myocardial fibrosis in type 2 diabetes mellitus mice by down-regulating p38MAPK signaling and inhibiting pyroptosis
Objective:To explore the effect of 8-week treadmill exercise on myocardial fibrosis in mice with T2DM and its molecular mechanism.Method:Eight m/m mice were used as the control group,and 32 db/db mice were randomly divided into control group,model group,exercise intervention group,inhibitor alone group and exercise combined with in-hibitor intervention group.Fasting blood glucose was monitored weekly.After 8 weeks,triglycerides(TG)and total cholesterol(TC)were measured.Masson staining was used to observe the degree of myocardial fibrosis,and immunofluorescence staining was used to observe the expression of Collagen Ⅰ and α-SMA.Westem Blot was used to detect the expression levels of fibrosis,inflammation,pyroptosis and p38MAPK related proteins.Result:The model group showed a significant increase in fasting blood glucose,TG and TC(P＜0.0001),Col-lagen Ⅲ(P＜0.05)and TGF-β1(P＜0.01)expression compared with control group.Compared to the model group,Masson staining in the other groups showed a significant improvement in disordered myocardial cell ar-rangement and a decrease in blue collagen fibers between the interstitial tissue and perivascular tissue;immuno-fluorescence staining also showed that the expression levels of Collagen Ⅰ and α-SMA and the expression lev-els of fibrosis-related proteins were significantly decreased in these groups.The expression levels of inflamma-tion and pyroptosis related proteins in the exercise intervention group were significantly lower than those in the model group.Compared to the model group,the phosphorylation level of p38MAPK in the exercise inter-vention group and the simple inhibitor group was significantly decreased(P＜0.05,P＜0.01),but the phosphory-lation level was not further decreased after the combined intervention.Compared to the model group,the ex-pression levels of NLRP3 and GSDMD-N in the single inhibitor group were significantly decreased(P＜0.05),and the combined intervention further inhibited the expression of Caspase-1(P＜0.05),Cleaved-Caspase-1(P＜0.05),and GSDMD-N(P＜0.001).Conclusion:Eight-week treadmill exercise can significantly improve myocardial fibrosis in db/db mice.The mechanism may reduce the phosphorylation of p38MAPK and pyroptosis of cardiomyocytes,thus improving myocardial fibrosis in db/db mice.The combination of treadmill exercise and SB203580 can further reduce py-roptosis.
万方数据
维普
