Preventive effect of Toll-like receptor 4 agonist LPS on myocardial ischemia-reperfusion injury in rats and its mechanism
Objective To investigate the preventive effect of Toll-like receptor 4(TLR4)agonist Lipopolysaccha-rides(LPS)on myocardial ischemia-reperfusion injury(MIRI)in rats and its mechanism.Methods Sixty rats were di-vided into the LPS intervention group(0.1 mg/kg,0.5 mg/kg,1 mg/kg,all were small doses),verapamil intervention group,model group and sham operation group,with 15 rats in each group.At 7 days before the establishment of MIRI models,rats in the LPS intervention group were given intraperitoneal injection of 0.1 mg/kg,0.5 mg/kg and 1 mg/kg LPS,rats in the verapamil intervention group were given intraperitoneal injection of 2.5%verapamil(2 mg/kg),rats in the sham operation group and model group were given intraperitoneal injection of equal volume normal saline.All were per-formed once a day.Then,except for the sham operation group,rats in the other groups underwent ischemia-reperfusion treatment.At 72 h after treatment,the cardiac function of rats in each group was detected by ultrasound,the myocardial histopathological changes were observed by hematoxylin-eosin(HE)staining,and the myocardial infarction size was ob-served by 2,3,5-triphenyltetrazolium chloride(TTC)staining.The proteins of forkhead box proteinO3a(FoxO3a),phos-pho-forkhead box protein O3a(pFoxO3aS253),Beclin-1 and LC in rat myocardial tissues were detected by Western blot-ting.Results Compared with the sham operation group,left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)decreased(both P<0.05),myocardial injury was more serious and the percentage of myocar-dial infarction area increased(both P<0.05),the relative expression of pFoxO3aS253 protein in the myocardial tissues de-creased(P<0.05),and the relative expression levels of FoxO3a,Beclin-1,and LC proteins increased in the model group(all P<0.05).Compared with the model group,LVEF and LVFS increased in the verapamil intervention group and LPS intervention group(both P<0.05);there was no obvious improvement in cardiomyopathy in the 0.1 mg/kg and 0.5 mg/kg LPS intervention groups,and the degree of myocardial fibrosis edema,fracture,necrosis and inflammatory cell infiltration were reduced in the verapamil intervention group and 1 mg/kg LPS intervention group;the percentage of myocardial infarc-tion area decreased(all P<0.05),the relative expression level of pFoxO3aS253 protein increased(P<0.05),and the rela-tive expression levels of FoxO3a,Beclin-1 and LC proteins decreased in the verapamil intervention group and LPS interven-tion group(all P<0.05).Conclusion Low-dose TLR4 agonist LPS can prevent MIRI in rats,and its mechanism may be related to promoting phosphorylation of FoxO3a and inhibiting activation of Beclin-1 and LC.
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