| Background: With the change of national life style, the aging of population and the acceleration of urbanization, the prevalence rate of cardiovascular disease in China is in a rising phase, and the prevalence of heart failure is increasing year by year.Previous studies have demonstrated that, heart failure is a clinical syndrome,caused by series of complex pathophysiological mechanisms, including inflammation.Persistent presence of inflammatory response can damage myocardial cells.Both apoptosis and autophagy could be observed in cardiac myocytes of heart failure.However, the role of autophagy in the heart which is protective or harmful has not yet been concluded. In Clinical observations,trimetazidine and rosuvastatin can reduce the level of the inflammatory factors and improve heart function in patients with heart failure. However, the application in heart failure is lack of evidence, and there are few studies on the effects of myocardial apoptosis and autophagy.Objects:To study the level of Inflammatory factors, cardiac function, apoptosis and autophagy in cardiac myocytes and the impact of these indicators after using trimetazidine or rosuvastatin after stimulating by LPS in heart failure rats after myocardial infarction.To investigate the effect of autophagy on the heart and the effect of inflammatory factors on the level of apoptosis and autophagy in rats with myocardial infarction.Methods:This experiment prepare 40 heart failure models after myocardial infarction model by ligating Left Anterior Decending of Wistar adult male rats and raise four weeks,sham operation group(sham group, n = 10)(without ligation of the left anterior descending and the remaining steps). We randomly selected 30 given intraperitoneal injection of LPS(lipopolysaccharide) as a stimulus in the successful preparation of heart failure rat model 40, and another 10 as model group(model group). According to whether the drug was given,given LPS stimulated rats were randomly divided to without treatment group(model+LPS group), trimetazidine group(QMTQ group) and rosuvastatin group(RSFTT group). After 4 weeks of treatment,evaluating cardiac function by echocardiography and hemodynamics,testing the level of NT-pro BNP, hs-Tn T, IL-6, hs-CRP, TNF-? by ELISA method. After left ventricular sampling, performing HE staining,Masson staining, TUNEL and DAPI staining to observe myocardial pathological changes, myocardial fibrosis and the level of apoptosis. Sampling from Left ventricular infarction edge area, detecting the expression of autophagy related protein LC3 B, P62 by Western-Blot, detecting the levels of autophagy related genes Beclin1, Atg5, Atg7, Atg14 m RNA expression by RTQ-PCR.Results:1.After the experiment,rats in each group were alive; compared with sham group,body weight of the rats in the model group decreased significantly(P<0.05).The difference between other groups was no statistical significance.The cardiac index reflecting theventricular remodeling and the lung indexand reflecting the severity of heart failure were increasing in the model group and decraesingthe in the two medication groups, but the difference was not statistically significant.2.The levels of IL-6, hs-CRP, TNF-?,NT-pro BNP, hs-Tn T were measured by ELISA method:Compared with sham group, the levels of inflammatory factors and hs-Tn T in the model group were significantly higher(P<0.01).Compared with the model group, the model+LPS group had no changed. Compared with the model+LPS group, the levels of inflammatory factors and hs-Tn T, NT-pro BNP were significantly lower than those of the two medication groups(P<0.05 or P<0.01).3.Cardiac function by echocardiography and hemodynamic showed that the cardiac function of model group was significantly decreased compared with the model group, the model+LPS group had no changed.Compared with the model+LPS group, the cardiac function was significantly improved in the two medication groups.4.HE staining and Masson staining: In the model group, the myocardial cells arranged in disorder, myocardial cell swelling and myocardial and vascular side visible large amounts of collagen fibers. Model+LPS group compared with the model group had no changed.Compared with model+LPS group,in the two medication groups,the myocardial cell disorders and cell swelling was improving,and collagen fibers in cells and perivascular was reducing.5.The results of TUNEL and DAPI staining showed that the level of apoptosis in the model group was up, and there was no change in the model+LPS group compared with the model group, and the apoptosis level of the two groups was decreased compared with the model+LPS group.6.Western-Blot and RTQ-PCR results indicate that the synthesizing of autophagosome in model group were reducing and the level of autophagy was declining comparing with the model group. No change in the level of autophagy between model+LPS group and the model group.Compared with model+LPS group,in the two medication groups,the synthesizing of autophagosome was increasing, the flow of autophagy was smoothing and level of autophagy raised.Conclusions:1.For heart failure rats after myocardial infarction,myocardial injury induced by inflammation can make heart failure worse.The mechanism may be related to the increasing of myocardial apoptosis and the decreasing of autophagy mediating by inflammatory reaction.2.Trimetazidine and rosuvastatin indirectly regulate the level of myocardial apoptosis and autophagy,reducing apoptosis and increasing autophagyby inhibiting the inflammatory response,to delay the progressive of haert failure after myocardial infarction baseing on the protection on the myocardial cells.3.Speculating that autophagy in myocardial cells has a protective effect in the heart. |
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