| Objective:Myocardial ischemia/reperfusion injury(MI/RI)is a myocardial ischemia-hypoxic disease induced by coronary artery disease.It has a rapid onset,short course of disease and high mortality.The clinical treatments and drugs often used are not effective,and there are some problems such as cardiotoxicity,insufficient intravenous administration or immature technology.The mortality rate of MI/RI patients is still high.Therefore,looking for a more efficient therapeutic drug has a very important effect on alleviating ischemia and improving the survival rate of patients.Naringin(Nar)has a significant mitigation effect on alleviating MI/RI,and it has the effects of anti-inflammatory,inhibiting cell apoptosis,reducing oxidative stress and other effects.It has been proven to be effective in a variety of diseases,and its cardioprotective effect is also very significant.In addition,naringin also has good drug-making properties,among which antitussive and expectorant effects are particularly good.Naringin tablets have been approved for use in antitussive and phlegm drugs to enter Phase I clinical trials.Compared with the drugs currently used in clinical treatment of MI/RI,naringin has the advantages of abundant sources,no serious adverse reactions,convenient access,and low cost.However,naringin in the treatment of MI/RI has not yet been clinically applied.The reason is that the specific mechanism of naringin in the treatment of MI/RI has not yet been elucidated,and most studies are pretreatment administration.Can not explain its therapeutic effect.This subject is based on the above research,and plans to carry out research on the treatment and mechanism of naringin on MI/RI rats.Methods:1.To Verify the protective effect of naringin on MI/RI in vitro,and simulate MI/RI by establishing hypoxia/reoxygenation(H/R)injury of rat H9c2 cardiomyocytes.Use cell viability detection and myocardial injury marker detection to determine the success of the model,and verify its effect based on the effects of different concentrations of naringin on the cell viability and myocardial injury markers of rat H9c2 cardiomyocytes after H/R injury.2.After the in vitro verification is effective,the in vivo verification and preliminary study of the mechanism are carried out.The key to the in vivo experiment lies in modeling.At present,the commonly used methods are all surgical modeling,which are mainly two methods: the rapid heart compression ligation under the chest without a ventilator,and the open chest ligation under the ventilator.This subject uses the latter to establish the MI/RI model.The results show that compared with the model without a ventilator,the mortality of rats during the modeling process can be effectively reduced when the ventilator is connected,and the postoperative recovery is faster and better,the modeling success rate is higher.Subsequently,Evans Blue-2,3,5-triphenyltetrazolium chloride(TTC)counterstaining,ECG monitoring,and myocardial injury marker detection were used to evaluate the success of the model.Real-time ECG monitoring is an important reference for subsequent experimental operations.3.In order to explore the mechanism by which naringin regulates the mitigation of MI/RI rat heart damage,drug intervention was carried out at the cellular level,and pyroptosis activator was added to H9c2 cells,and it was found that the H/R damage of the cells was aggravated,the inflammatory response was aggravated,and the expression of inflammasomes was significantly increased.Therefore,it is believed that MI/RI rat myocardial injury can induce cell pyrolysis,which in turn induces excessive activation of inflammasomes,and naringin can be used as an inhibitor of pyrolysis to inhibit MI/RI.The excessive outburst of inflammation in rats and the over-activated inflammasomes alleviate the pyrolysis induced by heart injury in rats and relieve the symptoms of myocardial injury.Results:1.Hypoxia for 8 hours and reoxygenation for 2 hours can successfully construct the H/R injury model of rat H9c2 cells.2.80μM naringin treatment for 4h is the best concentration and time.3.Naringin can reduce the damage of myocardial cells in rats with H/R injury.4.Through ECG monitoring,pathological changes and detection of related injury factors,it is judged that the MI/RI rat model can be successfully constructed after 30 minutes of ischemia and 2 hours of reperfusion.5.Naringin can reduce myocardial injury in MI/RI rats,improve pathological myocardium,and change the activity of myocardial injury markers.6.Naringin can reduce the production of inflammatory factors and reduce the expression of pyrolysis-related proteins.7.LPS and nigericin can effectively induce the pyrolysis of rat H9c2 cardiomyocytes.8.Nar can inhibit the damage of cardiomyocytes caused by H/R,LPS and nigericin.9.Nar can inhibit H/R,LPS and nigericin-induced pyrolysis and inflammation.Conclusion:In summary,naringin reduces pyrolysis by inhibiting inflammasomes,thereby alleviating heart damage in MI/RI rats. |
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