Regulation Of TGF-Beta 1/Smad And Its Related MiRNA In Exercise Intervention On The Fornation Of Diabetic Myocardial Fibrosis

Purpose:To investigate the occurrence and development of myocardial fibrosis and the intervention effect of aerobic exercise in type 2 diabetes mellitus,and the regulation of TGF-beta 1/Smad and its related miRNA in exercise intervention on the fornation of diabetic myocardial fibrosis.Method:In 35 4-week-old Sprague Dawley rats,10 rats were used as control group(NC group,n=10),the rest of rats were intraperitoneally injected with STZ to replicate type 2 diabetic rat model based on high-fat diet.After successful modeling,they were immediately divided into diabetic control group(DMC group,n=10)and diabetic exercise group(DME,n=10).The exercise group performed 60 minutes of no-load swimming training every day.Then,the serum FBG and INS levels were measured.After 8 weeks,the mRNA expression of TGF-?1,miR-133a,miR-21,miR-29b,Smad2,Smad 3,Smad 7,type I and type III collagen fibers was detected in each group of rats.Result:(1)At the end of 8 weeks after successful modeling of T2DM rats,compared with NC group,FBG content and HOMA-IR were significantly increased in DMC group(P<0.05).At the same time,the content of INS increased,but no significant difference.Compared with DMC group,the FBG content in the DME group was significantly lower(P<0.05),the INS content increased and the HOMA-IR decreased,but there was no significant difference.Compared with NC group,the contents of FBG and INS in DME group increased,there was no significant difference,and HOMA-IR increased significantly(P<0.05).(2)At the end of 8 weeks after successful modeling of T2DM rats,compared with NC group,the levels of TGF-?1 and mRNA expression of type ? and type ? collagen fibers in DMC group were significantly increased(P<0.05).Compared with DMC group,the content of TGF-?1 and mRNA expression of type ? and type ? collagen fibers in DME group were all significantly lower(P<0.05).Compared with NC group,the content of TGF-?1 and mRNA of type I and type III collagen fibers in DME group were all decreased,but there was no significant difference.(3)Compared with NC group,the expression of Smad2 mRNA in myocardium of DMC group was significantly increased(P<0.05),The expression of Smad3 mRNA was significantly increased(P<0.01)and Smad7 mRNA expression decreased,but no significant difference.Compared with DMC group,the expression of Smad2 mRNA was significantly decreased in the myocardium of DME(P<0.05),while the expression of Smad3 mRNA was significantly decreased(P<0.01),while the expression of Smad7 mRNA was significantly increased(P<0.01).Compared with group NC,the mRNA expression of Smad2 and Smad3 in myocardium of DME group increased,there was no significant difference,and the expression of Smad7 mRNA increased significantly(P<0.01).(4)Compared with NC group,the expression of miR-133a and miR-29b in myocardium of DMC group were significantly decreased(P<0.05),while the expression of miR-21 was significantly increased(P<0.05).Compared with DMC group,the expression of miR-133a and miR-29b in myocardium of DME group increased significantly(P<0.01).Meanwhile,miR-21 expression decreased,but there was no significant difference.Compared with the NC group,the expression of miR-133a and miR-29b in the myocardial tissue of DME group increased significantly(P<0.01),and the expression of miR-21 increased,but there was no significant difference.Conclusion:(1)The model of type 2 diabetic rats were successfully replicated in this study.A certain degree of fibrosis appeared in the myocardium of T2DM rats.Through 8 weeks of aerobic exercise,the occurrence and development of myocardial fibrosis in rats can be prevented.(2)With the development of T2DM,on the one hand,it can effectively inhibit the expression of miR-133a,thereby activating TGF-?1/Smad2?Smad3 signaling pathway,inhibiting the expression of miR-29b and promoting the generation of collagen.On the other hand,diabetes induces the over expression of TGF-?1,promotes the production of miR-21 and inhibits the expression of Smad7,thereby weakening the inhibition of Smad7 on TGF-?1/Smad signaling pathway,reducing the inhibition of collagen synthesis,and promoting the process of myocardial fibrosis.(3)Eight-week aerobic exercise can promote the expression of miR-133a on the one hand,inhibiting the TGF-?1/Smad signaling pathway,increasing the expression of miR-29,effectively reducing the synthesis of collagen,and preventing the occurrence of myocardial fibrosis in rats.On the other hand,8 weeks of aerobic exercise can reduce the expression of miR-21 by inhibiting the expression of TGF-?,thereby promoting the expression of Smad7,further inhibiting the TGF-?1/Smad signaling pathway,effectively reducing the synthesis of collagen and preventing the development of myocardial fibrosis.