Studies On The Mechanism Of Early Extracorporeal Cardiac Shock Wave Therapy To Relieve Myocardial Fibrosis By Inhibiting TGF-β1-Smad2/3-MMP-9 Signaling Pathways

Background: Ischemic heart disease(IHD)is a major cause of death worldwide and poses a great threat to human life and health.Cardiac shock wave therapy(CSWT)is a safe,non-invasive vascular regeneration therapy that can improve myocardial blood flow and improve cardiac function.This study further explored the role of CSWT in anti-myocardial fibrosis,reverse ventricular remodeling and improve the prognosis of IHD patients through the TGF-β1-Smad2/3-MMP-9signaling pathway.Objectives: To investigate whether early CSWT relieve s myocardial fibrosis by inhibiting the TGF-β1-Smad2/3-MMP-9 signaling pathway,and to provide a basis for the clinical application of CSWT against IHD ventricular remodeling.Methods: Rats were divided into sham group(sham group),acute myocardial infarction group(AMI group),acute myocardial infarction + extracorporeal cardiac shock wave treatment group(AMI + CSWT group),acute myocardial infarction +TGF-β1 receptor inhibitor group(AMI + SB431542 group)and acute myocardial infarction + extracorporeal cardiac shock wave treatment + TGF-β1 receptor inhibitor group(AMI + SB431542 group).+SB431542+CSWT group),6 in each group.Each group underwent echocardiography on day 4 after AMI,and the AMI + SB431542 and AMI + SB431542 + CSWT groups received SB431542 intervention at the end of echocardiography for 3 consecutive days,and CSWT treatment was started on day 7after surgery in the AMI + CSWT and AMI + SB431542 + CSWT groups for The treatment was continued for one month,and the groups continued to be observed for one month after the end of CSWT treatment,and echocardiography was performed again at the end of observation.After the examination of each group,HE staining and Masson staining were used to detect the degree of fibrosis,and Western blot was used to detect the changes of protein expression related to TGF-β1-Smad2/3-MMP-9signaling pathway and COL-I and COL-III protein expression levels.Results:1.Day 4 echocardiography results showed that the left ventricular cavity was significantly enlarged(p < 0.05)and cardiac function was significantly decreased(p <0.05)in the AMI group,AMI + CSWT group,AMI + SB431542 + CSWT group,and AMI + SB431542 group compared with the sham group.2.Day 62 echocardiography results showed that EF and FS were significantly lower(p < 0.05)and LVEDV and LVESV were significantly higher(p < 0.05)in the AMI group compared with the sham group;EF and FS were significantly higher(p <0.05)and LVEDV and LVESV were significantly lower in the AMI+CSWT group compared with the AMI and sham groups(p < 0.05);compared with the AMI+CSWT group,there were no significant differences in EF,FS,LVEDV,and LVESV in the AMI+SB431542+CSWT group(p > 0.05).3.HE staining results showed that myocardial fibers were disordered and inflammatory cells were increased in the AMI group compared with the sham group,and myocardial cells were more neatly arranged and inflammatory cells were reduced in the AMI+CSWT group compared with the AMI group.4.Masson staining showed that collagen fibers were significantly increased and CVF was significantly higher in the AMI group compared with the sham group(p <0.05);the percentage of collagen was significantly lower in the AMI+CSWT group compared with the AMI group(p < 0.05);and the degree of fibrosis was increased in the AMI+SB431542+CSWT group compared with the AMI+CSWT group,but no significant difference(p > 0.05).5.Western blot assay showed that hat the expression levels of TGF-β1,Smad3,MMP-9,COL-I and COL-III were significantly higher in the AMI group compared with the sham group(p < 0.05),and Smad2 content tended to increase,but there was no significant statistical difference(p > 0.05);compared with the sham and AMI groups,the expression levels of TGF-β1,Smad2,Smad3,MMP-9,COL-I and COL-III were significantly lower in the AMI+CSWT group(p < 0.05);compared with the sham and TGF-β1,Smad2,Smad3,MMP-9,COL-I and COL-III expression levels were significantly lower in the AMI+CSWT group compared with the sham and AMI groups(p < 0.05);compared with the AMI+CSWT group,the relative protein levels of TGF-β1,Smad2,Smad3 and MMP-9 were significantly lower in the AMI+SB431542+CSWT group(p < 0.05),and COL-I and COL-III protein contents were increased(p < 0.05).Conclusions:1.Early CSWT improves cardiac function,inhibits myocardial fibrosis and intervenes in ventricular remodeling.2.Early CSWT relieves myocardial fibrosis associated with the TGF-β1-Smad2/3-MMP-9 signaling pathway.