Moderate Intensity Aerobic Exercise Improves Myocardial Fibrosis in Db/db Mice Byincreasing Fgf21and Inhibiting Nlrp3levels

PURPOSE: This study was to investigate the effect of moderate intensity aerobic exercise on diabetic myocardial fibrosis via observing the expression levels of FGF21 and NLRP3 in db/db mice. METHODS: Thirty-two male db/db mice were randomly divided into sedentary groups (group D and group DI) and exercise groups (group DE and group DEI), eight mice in each group. The mice in exercise groups received 12 weeks of treadmill exercise at the intensity of 55% VO2max with the frequency of 50 minutes per times, 5 days per week. The mice in groups DI and DEI received Mcc950 (with dose 10 mg/Kg via i.p.) of three times per week to specifically inhibit the expression of NLRP3 and reduce inflammatory reaction. Mice were weighed, the body compositions were measured, the morphology and fibrosis of the myocardial tissue was observed by HE and Masson staining respectively, the expression levels of FGF21, FGFR1, NLRP3 and ASC were measured by immunofluorescent staining. RESULTS: The body weight of mice in DE(35.46 ± 1.95 g), DI(34.58 ± 2.05 g) and DEI(30.63 ± 2.51 g) groups were significantly lower than that in group D(40.28 ± 1.25 g) (P < 0.01). The volume fraction of myocardial collagen in DE(48.09 ± 1.66%), DI(47.3 ± 2.75%) and DEI(42.34 ± 1.31%) groups was significantly lower than that in D(58.61 ± 2.38%) group (P < 0.05). Compared with group D(59.01 ± 2.13)(69.77 ± 0.49), the protein expression level of FGF21 and FGFR1 of mice in group DE(87.97 ± 3.98)(107.2 ± 2.29) and group DEI (115.5 ± 3.40) (116.5 ± 7.6)increased (P < 0.05). While there was no difference for the expression of FGF21 related protein between group DI (63.89 ± 2.64) (72.77 ± 2.5) with group D. Compared with group D(92.1 ± 1.08)(214.3 ± 1.17), the protein expression level of NLRP3 and ASC of mice in group DE(56.27 ± 0.85)(190.5 ± 4.23) and in group DI (54.16 ± 0.97)(201.9 ± 3.68) decreased (P < 0.05, P < 0.01). Compared with group DI, the expression level of NLRP3 protein of mice in DEI(46.14 ± 0.85) group decreased (P < 0.05). CONCLUSIONS: Moderate intensity aerobic exercise can alleviate myocardial fibrosis in diabetes, by increasing expression of FGF21 and inhibiting the expression of NLRP3 related protein. ACKNOWLEDGEMENTS: This study was supported by the fundamental research funds for the Central Universities of China (2021TD012).