Objectives To investigate the protective effect and mechanism of triggering receptor expressed on myeloid cells 1(TREM1)inhibitory peptide LR12 on myocardial ischemia-reperfusion injury(MIRI)in rats.Methods Forty-eight SD rats were randomly divided into sham operation group(sham group),ischemia reperfusion group(I/R group),LR12-scrambled group(LR12-scr group),and LR12 group,with 12 rats in each group.Rat models of MIRI were established and intraperitoneal injection of LR12 and LR12-scrambled intervention were performed 5 min before reperfu-sion.After modeling,the cardiac function of rats was detected by small animal ultrasonography.The myocardial injury was observed by hematoxylin-eosin(HE)staining.The myocardial infarction area was measured by TTC staining.Serum concentrations of cardiac troponin I(cTnI),creatine kinase isoenzyme(CK-MB),myoglobin(MB),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β)were determined by enzyme-linked immunosor bent assay(ELISA).Toll-like receptor 4(TLR-4),myeloid differentiation factor 88(MyD88),nuclear factor kappa-B(NF-κB p65),NF-κB inhibitor α(IκBα)and TREM1 protein expression levels in myocardial tissues were detected by Western blot.Results Compared with sham group,the pathological damage of myocardial tissue in I/R group was serious,the cardiac function was abnormal,and the area of myocardial infarction was significantly increased(P<0.05),the serum concentrations of cTnI,CK-MB,MB,TNF-α,IL-6 and IL-1β were significantly increased(P<0.05),meanwhile,the expression levels of TLR-4,MyD88,NF-κB p65 and TREM1 in myocardial tissue were significantly increased(P<0.05),while the expression level of IκBα protein was significantly decreased(P<0.05).Compared with I/R group,the patho-logical injury of myocardial tissue and cardiac function were significantly improved in LR12 group,and the area of myocar-dial infarction was significantly decreased(P<0.05),the serum concentrations of cTnI,CK-MB,MB,TNF-α,IL-6 and IL-1β were significantly decreased(P<0.05),meanwhile,the expression levels of TLR-4,MyD88,NF-κB p65 and TREM1 in myocardial tissue were significantly decreased(P<0.05),while the expression level of IκBα protein was signifi-cantly increased(P<0.05),thus there were no significant differences in the above indexes between LR12-scr group and I/R group(P>0.05).Conclusions TREM1 inhibitory peptide LR12 can alleviate the inflammatory response by blocking the TLR-4/NF-κB signaling pathway,and thus improve myocardial ischemia-reperfusion injury.
维普
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