| Background:Myocardial fibrosis is the key part of ventricular remodeling after myocardial infarction.Fibrosis after myocardial infarctioncan increase the myocardial stiffness,reduce the systolic and diastolic function of ventricular,cause arrhythmia,and even can cause sudden death in severe cases,which is an important factor causing heart failure.Therefore,early prevention and reversal of myocardial fibrosis is of great significance.The timely and effective regulation of myocardial fibrosis is directly related to the prognosis of myocardial infarction.At present,there are no effective drugs for the treatment of anti-myocardial fibrosis,and the mode of overall regulation and syndrome differentiation of traditional Chinese medicines has certain advantages and features in the prevention and treatment of cardiovascular diseases.Therefore,to explore the effect of Yiqihuoxue Chinese medicine on myocardial fibrosis after myocardial infarction and the related mechanisms are expected to provide new clinical treatment ideas and drug treatment targets for the prevention and treatment of myocardial fibrosis.Objectives:Explore the possible mechanism of improving myocardial fibrosis by observing the effect of Yiqihuoxue drug on fibrosis after myocardial infarction in rats.Methods:An animal model of acute myocardial infarction was established by ligaturing the left anterior descending coronary artery of rats.The male SD rats were randomly divided into three groups:the myocardial infarction group,the Yiqihuoxue group,the perindopril group and an another set of sham operation group(only open the chest and thread the string without ligation).There are two observation time points:the 7thday and 28thday.All groups of rats were given intragastric administration 24 hours after surgery.The structural and functional changes of the heart of rats in each group were detected by echocardiogram;the effects of the drugs on Pathological changes in myocardial tissue were observed by HE staining;the ultrastructural changes in the heart was observed by transmission electron microscope;the arrangement of myocardial collagen fiber were evaluated by masson staining;the distribution of fibers and the proliferation of collagen was observed by immunohistochemical staining;the protein expression levels of collagen I,collagen III,transforming growth factor(TGF-(31)and connective tissue growth factor(CTGF),β-catenin protein was tested by western blot;the gene expression levels of TGF-β1,CTGF,β-catenin was tested by RT-PCR.Results:Experiment 1:1.The results of cardiac structure and function changes in rats:at the 7th day after myocardial infarction,LVIDd,LVIDs,LV Vol d,LV Vol s in the model group were higher(P<0.01,P<0.01,P<0.01,P<0.01),LVFS and LVEF were significantly lower than those in the sham operation group(P<0.01,P<0.01),indicating that the cardiac function decreased seriously after myocardial infarction;after treatment of Yiqihuoxue drugs,LVIDd,LVIDs,LV Vol d,LV Vol s showed a downward trend,but there was no statistical difference between Yiqihuoxue group and the model group in LVIDdLVIDs(P>0.05,P>0.05),LVFS、LVEF of rats in Yiqihuoxue group were significantly higher than those of the model group((P<0.01,P<0.01).At the 28th day after myocardial infarction,the indices of cardiac function in the model group were similar to those of the 7th(P<0.01,P<0.01,P<0.01,P<0.01),LVIDd、LVIDs、LV Vol d、LV Vol s of rats in Yiqihuoxue group decreased compared with the model group.But there was no statistical difference between Yiqihuoxue group and the model group in LVIDs(P>0.05).LVFS、LVEF of rats in Yiqihuoxue group were significantly higher than those of the model group and the differences were statistically significant(P<0.05,P<0.01),indicating that the improvement of cardiac function of Yiqihuoxue group is obvious.2.The results ofpathological changes in myocardial tissue in rats:at the 7 th and 28 th day after myocardial infarction,under the optical microscope,the shape of myocardial fibrosis in the infarct margin of the model group was abnormal,indicating that the myocardial structure was severely damaged after myocardial infarction;after treatment,the pathological changes of myocardial structure in twodrug groups were alleviatedto varying degrees,and the degree of myocardial structural damage was greatly improved compared with the model group.Under the transmission electron microscope,myocardial sarcomere broke down,part of the mitochondria swelled and deformed,a large amount of collagen was seen around the blood vessels and at the fracture,fibroblasts proliferated,and mitochondria became severely damaged in infarct margin of the model group.The ultrastructural damage of heart in the twodrug groups were alleviated compared with the model group.3.The results of changes in collagen fibers of myocardial tissue in rats:at the 7th and 28th day after myocardial infarction,rats in model group showed extensive distribution of collagen fibers,connective tissue hyperplasia,severe fibrosis;the degree of collagen hyperplasia in the two drug groups was significantly reduced compared with the model group,and the extent of myocardial fibrosis was also greatly reduced.4.The results of expression of collagen I and collagen III of myocardial tissue in rats:at the7 th and 28 th day after myocardial infarction,in infarct area and infarct margin of the model group,dense dark brown granules with large areas were observed,the positive expression of collagen Ⅰ and collagen Ⅲ was significantly higher than that of the sham operation group,which indicated that the deposition of collagen Ⅰ and collagen Ⅲ was significantly increased after myocardial infarction.Compared with the model group,the infiltration range of positive expression particles of collagen Ⅰ and collagen Ⅲ was reduced to a certain extent in the two drug groups,indicating that Yiqihuoxue drugs could inhibit myocardial fibrosis by reducing the deposition of collagen Ⅰ and collagen Ⅲ.Experiment 2:1.The protein expression of collagen Ⅰ,collagen Ⅲ,TGF-β1 CTGF and β-catenin of myocardial tissue in rats:at the7 th and 28 th day after myocardial infarction,compared with the sham group,the protein expression of collagen Ⅰ,collagen Ⅲ,TGF-β1,CTGF of the model group were all increased greatly(P<0.01,P<0.01,P<0.01,P<0.01),the protein expression of β-catenin was also significantly upregulated(P<0.01,P<0.05),However,the expression of fibrogenic factors and β-catenin proteins in the Yiqihuoxue group generally showed a downward trend,of which the reduction of the protein expression of collagenⅢ and CTGF is more obvious.2.The mRNA expression of TGF-β1,CTGF and β-catenin of myocardial tissue in rats:at the7 th and 28 th day after myocardial infarction,the results of gene expression of the three indices of myocardial tissue in each group were generally consistent with the protein expression results,indicating that Yiqihuoxue Pills could inhibit the development of myocardial fibrosis at the molecular level.Conclusions:1.Combined with a series of pathological changes of myocardial tissue after myocardial infarction in rats at the 1th and 4th week after infarction,it was confirmed that the rats showed obvious fibrosis after myocardial infarction,and Yiqihuoxue drugs could improve myocardial fibrosis of rats at pathological morphology.2.After treatment,the expression of fibrosis-related factors of myocardial tissue in ratscollagen Ⅰ,collagen Ⅲ,TGF-β1,and CTGF decreased,indicating that Yiqihuoxue drugs can improve myocardial fibrosis at the molecular level.3.Yiqihuoxue drugs can delay the progression of myocardial fibrosis in myocardial ischemic rats by down-regulating the expression of β-catenin,and provide a possible therapeutic target for clinical treatment of myocardial fibrosis. |
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