| BackgroundAcute Myocardial Infarction(AMI)is the leading cause of death in coronary heart disease.More and more studies have found that sympathetic excitability is an important compensatory mechanism for cardiac function reduction after myocardial infarction.Sympathetic nerve distribution abnormalities are closely related to arrhythmia and disease prognosis.At the same time,sympathetic remodeling is associated with sympathetic activity.Norepinephrine is the major neurotransmitter used in the sympathetic nervous system.Cardiac sympathetic nerve activity increases after MI,and chronic changes in NE transmission lead to electrical remodeling and ventricular arrhythmias.Yiqi Huoxue drugs is based on the classic prescription of Danggui Buxue Decoction.After years of extensive research in our research group,Yiqi Huoxue drugs have been confirmed by animal experiments and cell experiments that it can effectively inhibit the secretion of inflammatory factors and protect the myocardial structure of myocardial tissue after myocardial infarction.At the same time,through network pharmacology research to screen its effective target,and the pharmacological composition analysis of active ingredients,to more clearly define its mechanism of action.ObjectivesTo establish a rat model of myocardial infarction,and to observe the evaluation of the morphological structure,function,sympathetic nerve remodeling and the expression of sympathetic neurotransmitters norepinephrine and related transporters and receptors in Yiqi Huoxue.The mechanism of action of Yiqi Huoxue by regulating sympathetic nerve activity.MethodsA myocardial infarction model was established in a clean-grade(Sprague-Dawley)male healthy rat using a left anterior descending coronary artery(LAD)ligation.Rats with successful modeling were divided into model group,Yiqi Huoxue group,metoprolol tartrate group and sham operation group according to random number table method.It is divided into three time points:3th d,7th d,and 28th d.The corresponding dose of the drug or distilled water was administered to the stomach the next day after surgery.The structure and function of the heart were collected by animal ultrasound system.The pathological changes of myocardial morphology were observed by HE staining.The plasma and myocardial norepinephrine content were detected by ELISA.The stellate ganglion NET mRNA and the myocardial infarction zone β1 were detected by RT-PCR.-AR mRNA content;Western blot was used to detect the expression of NET,TH and NGF protein in the marginal zone of stellate ganglion;the expression of TH and NGF in the heart was observed by immunohistochemistry.To explore the effect of Yiqihuoxue on norepinephrine in rats after myocardial infarctionResultsExperiment 1:Observing the improvement of heart function and sympathetic nerve remodeling related factors after Yishen Huoxue medicine after myocardial infarction:1.Compared with the sham operation group,LVID,s and LVID,d in the model group were significantly increased at three time points(P<0.01).Compared with the model group,at the three time points,the LVID,s of the YQHX group and the Mt group were significantly reduced,with statistical significance(P<0.001 or<0.05),while the LVID,d of the two groups were reduced,without statistical significance.At three time points,LVEF and LVFS of the model group were significantly lower than those of the sham group(P<0.01).Compared with the model group,LVEF and LVFS in the YQHX group were significantly increased,both of which were statistically significant(P<0.01).2.HE staining:compared with the model group,on the third and 28th after the postoperative administration,the two groups had smaller inflammatory infiltration area and less exudation Compared with the model group,on the 28th day after the postoperative administration,the two groups had smaller myocardial fibrosis area and less scarring.3.At the three time points,TH and NGF proteins were significantly increased in the model group compared with the sham group(P<0.01).Compared with the model group,TH and NGF proteins,markers of sympathetic nerve,decreased significantly in the two groups(P<0.01 or P<0.05).Experiment 2:The effects of Yiqihuoxue drugs on norepinephrine,norepinephrine transporter and pi-AR after myocardial infarction in rats were observed.On the 28th d after postoperative administration,the expression of NE in the model Egroup decreased significantly(P<0.01).Compared with the model group,the content of plasma NE and myocardial NE in the two groups was significantly decreased on both 3th d and 7th d after the postoperative administration,with statistical significance(P<0.01 or P<0.05),and the content of plasma NE and myocardial NE in the two groups was significantly increased on the 28th d after the postoperative administration,with statistical signific.ance(P<0.01).2.Compared with the sham operation group,NET mRNA and NET protein expression in the infarct marginal area of the stellate ganglion in the model group were significantly decreased at three time points(P<0.01).Compared with the model group,NET mRNA and NET protein expressions in the stellate ganglion and the infarct marginal area were increased in the two groups at three time points,with statistical significance(P<0.01 or P<0.05).3.Compared with the sham group,the expression of β1-AR in the model group increased significantly on both 3th d and 7th d after postoperative adninistration,and decreased significantly on 28th d after postoperative administration(P<0.01).Compared with the model group,the expression of 1-ar gene in the YQHX group continued to decrease on both 3th d and 7th d after the postoperative administration,and the expression of β1-AR gene increased and approached the normal level on the 28th d after the postoperative administration(P<0.05).Conclusion1.Yiqihuoxue drugs improves left ventricular systolic and diastolic function and effectively inhibits the expression of sympathetic remodeling markers TH and NGF.2.Yiqihuoxue drugs can effectively regulate the content of myocardial and plasma NE after myocardial infarction at three time points after myocardial infarction,so as to balance the activity of sympathetic nerve.3.Yiqihuoxue drugs increased the expression of stellate ganglion and myocardial NET and myocardial β1-AR after myocardial infarction,further illustrating the regulation mechanism of norepinephrine after myocardial infarction. |
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