The Mechanism Study For The Treatment Of Myocardial Infarction Through Mechanical Loading

BackgroundMyocardial infarction(MI)is a myocardial necrosis caused by acute and persistent ischemia and hypoxia in coronary arteries.A series of complex changes after MI such as intense inflammatory reaction,cardiomyocyte apoptosis,necrosis and fibrosis,can cause abnormal ventricular remodeling,which seriously affects heart function and ultimately leads to heart failure.In addition to regular medicine and interventional therapy,exercise rehabilitation is a key point in cardiac rehabilitation.A physical rehabilitation treatment instrument-pulsed joint mechanical loading can simulate the active movement of the human body.Previous studies have shown that mechanical loading achieved the physical activity by mechanical stress on the synovial joints,and it has been confirmed that it can reduce the inflammatory response.However,the role of mechanical loading in improving myocardial injury in MI rats has not been reported.ObjectivesIn this study,male Wistar rats were used to establish a MI model by ligation of the left anterior descending coronary artery.Inflammatory response plays an important role in the development of MI.It is hypothesized that as a new type of physical rehabilitation therapy,mechanical loading can reduce the abnormal inflammatory response and restrict cardiac remodeling by down-regulating NF?B and MMP signaling pathways.MethodsThe experiment was divided into three groups: sham operation group(Sham),myocardial infarction model group(MI)and mechanical loading treatment group(MI+Loading).The loading conditions were 15 Hz,5 N,6 min/day,3 min per side,5 d/week,continuous loading for 2,4 and 8 weeks,respectively.Changes in body weight of the rats were recorded every 3 days.At the end of the treatment time,the rats were sacrificed.The electrocardiogram of the rats was detected before sacrifice.To observe the effects of mechanical loading on inflammatory response and ventricular remodeling in MI rats,rat hearts were isolated and detected by HE staining,TTC staining,Masson staining and immunohistochemical staining.Results Compared with the Sham group,MI resulted in a significant decrease in the survival rate in MI group,and loading treatment significantly improved the survival rate.Loading significantly reduced the infarct size caused by myocardial infarction.The Lead II ST-segment in MI group was significantly decreased(p < 0.05),but significantly improved after loading treatment(p < 0.05).The heart mass index and ventricular index of the rats significantly increased in MI group(both p < 0.05),and after mechanical loading they significantly decreased(both p < 0.05).The left ventricular wall thickness in MI group was significantly reduced(p < 0.05),but it was significantly improved after loading treatment(p < 0.05).Histologic staining results showed that MI caused inflammatory reaction and fibrosis in myocardial tissue.After loading therapy,the number of inflammatory cells and collagen volume fraction were significantly improved(both p < 0.05).Immunohistochemical analysis showed that MI resulted in increased expression of NF-?B p65,IL-6 and MMP-9,and mechanical loading inhibited the expression of them(all p < 0.05).Correlation analysis showed that there was a significant positive correlation between NF-?B p65 and IL-6,NF-?B p65 and MMP-9,and IL-6 and MMP-9(all p < 0.01).Conclusions Mechanical loading relieves inflammatory response after MI by reducing the expression of NF-?B p65 and IL-6.Meanwhile,it can alleviate ventricular remodeling by reducing MMP-9 expression.In summary,mechanical loading can significantly improve myocardial injury in MI rats,which may be related to reduce inflammation and inhibit ventricular remodeling.