| Purpose:to establish a rat model of myocardial infarction with high-dose isoproterenol（ISO）and investigate whether exogenous H2S can inhibit apoptosis through regulating Yap1/Taz pathway,so as to improve myocardial fibrosis after myocardial infarction in rats and its underlying mechanism.Method:Forty one male adult SD rats were divided into control group（n=10）,model group（n=13）,H2S blank group（n=6）and H2S intervention group（n=12）.The model group and hydrogen sulfide intervention group were given intraperitoneal injection of ISO（50mg/kg/d）for 2 days,once a day.The control group and H2S blank group given equal dose of normal saline injections of 2 d.The electrocardiogram and troponin of the four groups of rats were detected to observe the building success or not.A week later,H2S blank group and H2S intervention group were treated with Na HS in the same way（equipped with 56μmol/kg/d）,while control group and model group were treated with 0.9%Na Cl in the same way.The experiment for 6weeks,and color Doppler ultrasonography was performed.Anesthesia and kill the rats,and test the heart weight,and Calculate the heart weight index.The collection of myocardial collagen was observed by masson staining;HE dyed view the myocardial pathological form.Cell apoptosis was observed by Tunnel staining.The levels of Yap1,Taz,Bax,Bcl-2,Caspase9,MMP3,TIMP2,TGF-βand GAPDH were detected by WB method.Results:1.Compared with control group,H2S intervention group and model group the second lead ST segment and troponin T were significantly increased,in order to confirm the successful preparation of rat myocardial infarction model.2.Compared with the control group,the heart weight index increased in the model group and the H2S intervention group.And contrast model group,H2S blank group and H2S intervention group cardiac weight index decreased.3.Color Doppler ultrasound:compared with the normal group,the left ventricular end systolic diameter increased,the left ventricular end diastolic diameter and left ventricular short axis rate decreased in the model group,and the cardiac function also decreased significantly in the model group;compared with the model group,the left ventricular end systolic diameter decreased,the left ventricular end diastolic diameter and left ventricular short axis rate increased in the H2S intervention group（P<0.05）,And cardiac function also improved significantly.4.Masson staining:compared with control group,model group not only considerably increase the myocardial collagen fibers,and obvious myocardial cells in chaos;And contrast model group,H2S blank group and H2S intervention group not only myocardial cell arrangement is neat,and number of myocardial interstitial collagen fibers also fell.5.HE staining:Compared with the control group,the myocardial tissue in the model group showed significant fibrosis,vascular endothelial cell shedding etc.And contrast model group,H2S blank group and H2S intervention group above conditions pathological changes appear to be improved significantly.6.Tunnel staining:compared with control group,model group of myocardial cell shape is irregular,the number of brown stained nuclei increased significantly;Compared with model group,H2S intervention group myocardial cell shape is neat,The number of brown stained nuclei decreased significantly.7.WB detection:Compared with control group,the protein levels of Yap1,Taz,Bax,Caspase9,MMP3 and TGF-βin model group were increased（P<0.05）,while the protein levels of Bcl-2and TIMP2 were decreased（P<0.05）.Compared with the model group,the protein levels of Yap1,Taz,Bax,Caspase9,MMP3 and TGF-βdecreased in the H2S intervention group（P<0.05）,while the protein levels of Bcl-2 and TIMP2 increased（P<0.05）.Conclusions:Exogenous H2S can improve myocardial fibrosis induced by isoproterenol in rats after myocardial infarction,and its mechanism may be related to down regulating Yap1/Taz signaling pathway and inhibiting apoptosis. |
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