Study On The Protective Effect Of R-spondin3 On Myocardial Ischemia Reperfusion Injury

Background:Acute myocardial infarction(AMI)is one of the diseases with the highest morbidity and mortality in the world.Timely restoration of ischemic myocardial perfusion is the primary therapeutic principle for acute myocardial infarction.However,reperfusion injury may further aggravate the death of myocardial cells,which is known as myocardial ischemia reperfusion injury(MIRI).It reduces the benefits of reperfusion.Therefore,how to reduce reperfusion injury has naturally become the focus of research.The mechanism by which MIRI occurs is not fully understood.Excessive inflammatory response is one of the main mechanisms of myocardial ischemia reperfusion injury.Pro-inflammatory cytokines such as tumor necrosis factor a(TNF-a)and interleukin 6(IL-6)were significantly expressed and dominated.With percutaneous coronary intervention(PCI)popularization and development of the technology,more and more patients with myocardial infarction can receive PCI.But in the course of that treatment,the necessity of the application of antiplatelet and anticoagulant drugs is often emphasized.However,the use of drugs that inhibit inflammatory cytokines and reduce reperfusion injury is often neglected.Studies have shown that specific Roof plate-specific spondin(RSPO)is the secreted activator of Wnt/?-catenin signal.They potently enhance WNT signals by binding leucine-rich repeat-containing G protein-coupled receptors(LGRs)and increasing the availability of WNT receptors.They play a variety of roles in embryonic patterns and organ development.Of particular interest is R-spondin3(Rspo3),which plays an important role in the anti-overreaction of I/R inflammation.Method:SD rats were used to establish the MIRI model,to observe the dynamic changes and correlation of cytokines(TNF-a,IL-10 and IL-6)in the myocardial group and serum of early MIRI,and Rspo3was used to observe the effects on cytokine expression,myocardial infarction area and left ventricular function,and to explore the mechanism of action.Results:Our experiment proved that TNF-??IL-10 and IL-6 were significantly expressed in the myocardial tissue and serum of rats at the early stage of MIRI,and showed a dynamic change trend.The values of TNF-??IL-10 and IL-6 gradually increased for 2-4h after reperfusion,and then gradually decreased.After Rspo3 treatment,the expression of inflammatory factors was inhibited,the degree of cardiac fibrosis was improved,the infarct area was reduced,and the cardiac function of rats was improved.Conclusion:In summary,Rspo3 plays an obvious cardioprotective role in heart I/R.Therefore,we believe that Rspo3 is a promising clinical drug for the treatment of ischemic heart disease.