| Objective: To compare the effects of MOTS-c and aerobic exercise on cardiac structure and function in rats;To investigate the role of IGF-1/PI3K/Akt pathway in the physiological remodeling of the heart induced by MOTS-c and aerobic exercise.Methods: Thirty two six week old SPF male Sprague-Dawley rats were stochasticly divided into blank control group(Group C,n=8),MOTS-c group(Group M,n=8),aerobic exercise group(Group E,n=8),and aerobic exercise combined with MOTS-c injection group(Group ME,n=8).Group E and group ME received treadmill exercise intervention(20 m/min,slope 0 °,1 h/day,5 days/week,8 weeks in total);M group and ME group were injected with MOTS-c intraperitoneally(0.5 mg/kg/d,5days/week,8 weeks in total);Group C and Group E were injected intraperitoneally with the same dose of normal saline.Echocardiography was used to observe the structure and function of the heart in normal rats,HE staining and transmission electron microscopy were used to observe the morphological and ultrastructural changes of the myocardial tissue in rats,and q-RT PCR and Western blotting were used to detect the expression of molecular pathway m RNA and related proteins.Results:(1)From the perspective of basic indicators,there was no significant decrease in body weight and significant increase in cardiac weight index(HWI)among groups E,M,and ME compared to group C(p<0.05),but there was no significant difference between the three groups(p>0.05).(2)In general,compared to group C,myocardial fibers in groups E,M,and ME all increased in thickness,and similar changes were observed in these three groups,with a trend of hypertrophy.From the ultrastructure of the electron microscope,it can be seen that the myofibrils of the myocardium in groups E,M,and ME are arranged neatly,and the number of mitochondria is slightly increased.(3)From the perspective of physiological function indicators,compared with Group C,the cardiac LVPWD of rats in Group E and M was significantly increased(p<0.0001,p=0.0012),while the cardiac LVIDd,EDV,and E/A of rats in Group M,E,and ME were significantly increased(p<0.0001,p=0.008,p=0.0004,p=0.0047,p=0.0005).The cardiac ESV of rats in Group M,E,and ME was significantly increased(p=0.03,p<0.05,p<0.05),but there was no significant difference between groups(p>0.05)Cardiac SV,EF,and FS were significantly increased in group M,but there was no significant change between group ME and group C(p>0.05).(4)The results of q RT-PCR showed that compared with group C,the expression of IGF-1 m RNA in group E and M(p=0.02,p=0.001,p<0.05)was significantly increased,while the expression of IGF-1 m RNA in group ME was not significantly different from that in group C(p>0.05).The expression of PI3 K m RNA in group E,M,and ME had an upward trend,but there was no statistically significant difference(p=0.7,p=0.26,p=0.08).The expression of AKT m RNA in group E,M,and ME was also increased,Group M had a very significant increase(p=0.005,p<0.01);There was no significant difference between E and ME(p=0.91,p>0.05).Western blotting results showed that the expression of IGF-1 in group E and group M(p=0.026,p=0.027,p<0.05)was significantly increased compared with group C;The expression of PI3 K and AKT proteins in group E,M,and ME increased,but there was no significant difference(p=0.92,p=0.32,p=0.79,p=0.2,p=0.4,p=0.4);The expression of p-AKT protein in group E,M,and ME was significantly higher than that in group C(p<0.01,p=0.0004,p=0.05).Conclusion: MOTS-c can induce physiological hypertrophy of the heart similar to aerobic exercise.IGF-1/PI3K/AKT pathway may be one of the mechanisms that MOTS-c induces physiological remodeling of the heart. |
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