| Myocardial fibrosis is a common pathological change in the development of various cardiovascular diseases to a certain stage,the main feature of cardiac fibrosis is the accumulation of extracellular matrix proteins.It is a high risk factor in the prognosis of heart disease.Therefore,the prevention and reversal of myocardial fibrosis has been one of the focuses of clinical prevention and treatment of cardiovascular diseases.The main components of Fuzheng Huayu capsule include Salvia miltiorrhiza,peach kernel,pine pollen,Schisandra,Gynostemma pentaphyllum,and Cordyceps mycelium.Previous studies have confirmed that Fuzheng Huayu capsule has an improved effect on myocardial fibrosis,but its specific mechanism is not clear.TGF-?/Smads signaling pathway is closely related to myocardial fibrosis,and it has promoting effect on myocardial fibrosis.Based on this,this study intends to make rat acute myocardial infarction model,observe the effects of Fuzheng Huayu capsule on myocardial fibrosis and TGF-?1/Smads signaling pathway in model rats,and to explore the possible mechanism of Fuzheng Huayu Capsule in anti myocardial fibrosis.Objective To explore the effects of Fuzheng Huayu Capsule on myocardial fibrosis and its possible mechanism through the perspective of regulating TGF-?1/Smads signaling pathway.Methods Acute myocardial infarction?Acute Myocardial Infarction,AMI?model in rats was established by ligating the left anterior descending coronary artery,24 hours after the model was established,the model was randomly divided into several groups,including the model groupwithout drug intervention,the Fuzheng Huayu group,the captopril group and the sham-operation group.the sham-operation group was only threaded without ligatd.Fuzheng Huayu capsules(0.4g·kg-1·d-1)and captopril tablets(2.25mg·kg-1·d-1)were intragastrically administered to the Fuzheng Huayu group and the captopril group.The model group and sham-operation group were administered with the drug group and equal volume of deionized water,once daily,for 8 weeks.A small animal ultrasound imaging system was used to examine the changes of cardiac function and structure in rats:Tissues around the myocardial infarction were stained with HE and Masson's trichrome staining to detect the pathological changes of myocardial tissue:The expression of?-SMA and TGF-?1 was detected by immunohistochemistry.The expressions of smad3,p-smad3,samd4 and smad7 protein were detected by Western blotting.The mRNA expressions of TGF-?1,smad3,smad4 and smad7were detected by real-time fluorescence quantitative PCR.Results?1?Compared with the sham-operation group,the systolic function of the left ventricle in the model group was weakened or even disappeared,and the left ventricular volume was significantly increased;IVSd and IVSs became thinner,LVIDs and LVIDd increased,and LVEF and LVFS decreased significantly?P<0.05?.Compared with the model group,the ventricular wall contraction of the Fuzheng Huayu group and captopril group was improved,the level of left ventricular systole weakened,and the LVEF and LVFS were significantly higher?P<0.05?;the IVSs in the Fuzheng Huayu group were thickened.LVIDs became smaller?P<0.05?,IVSd became thicker and LVIDd decreased,but there was no statistical difference.In the captopril group,IVSd and IVSs became thicker and LVIDs decreased?P<0.05?.?2?HE pathological staining results showed that the sham-operation group had a well-ordered structure of myocardial fiberosis,the size and shape of the nucleus were relatively uniform.In the model group,typical myocardial infarction symptoms could be seen.The infarcted myocardium disappeared,the myocardial fibrinolysis was broken,the myocardial cells were broken,the nuclei contracted and deformed,and the original structure was lost.The non-infarcted myocardium fiberosiswere arranged relatively neatly.Compared with the model group,the arrangement of myocardial fiberosis in the Fuzheng Huayufang group and captopril group were neat,the degree of damage to the myocardial striae was also reduced,and the degree of contraction of the cell nucleus was also weak,but the situation was slightly worse than the sham-operation group.?3?Compared with the sham-operation group,the level of collagen in the border zone of the myocardial infarction was increased in the model group?P<0.01?.Compared with the model group,the Fuzheng Huayu group and the captopril group Collagen levels were decreased?P<0.01?.Compared with the sham-operation group,the?-SMA protein level of the myocardial infarct margin was increased in the model group?P<0.01?.Compared with the model group,the level of?-SMA protein in the Fuzheng Huayu group and the captopril group were decreased.?P<0.01?.?4?Compared with the sham-operation group,the expression of TGF-?1 protein in the infarct marginal zone of the model group was significantly higher than that in the sham-operation group?P<0.05?.The expressions of TGF-?1 protein in the Fuzheng Huayu group and captopril group were significantly reduced?P<0.05?.?5?Compared with the sham-operation group,the expression of smad3 in the model group increased,but the expression of p-smad3 protein increased?P<0.01?.Compared with the model group,the expression of smad3 in the Fuzheng Huayu group had a tendency to decrease,the expression of p-smad3 protein was significantly decreased?P<0.01?.?6?Compared with the sham-operation group,the expression of smad4 protein in the model group increased,while the smad7 protein expression decreased.Compared with the model group,the smad4 protein expression in Fuzheng Huayu group and captopril group was significantly decreased,the expression of smad7 protein showed an increasing trend,and only the captopril group was significantly different from the model group?P<0.05?.?7?Compared with the sham-operation group,the expression of smad3 and smad4 mRNA in the peripheral region of myocardial infarction in the model group increased?P<0.05?,the expression of smad7 mRNA decreased?P<0.05?.Compared with the model group,smad3 and smad4 mRNA in Fuzheng Huayu group and captopril group decreased?P<0.05?,the mRNA level of smad7 increased?P<0.05?.Conclusion Fuzheng Huayu capsule can improve myocardial fibrosis after myocardial infarction to a certain extent,its mechanism may be related to the effects of regulating TGF-?1/Smads signaling pathway,down-regulating the expressions of TGF-?1,smad3,smad4 and their mRNA and up-regulating samd7 and its mRNA. |
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