Objective To investigate the effect of ophiopogonin D on myocardial in rats with ischemia-reperfusion injury (MIRI) by regulating the sphingosine kinase 1 (SphK1)/sphingosine 1-phosphate (S1P)/sphingosine 1-phosphate receptor 1 (S1PR1) pathway. Methods Rats were randomly separated into MIRI group,ophiopogonin D group,SphK1 activator (K6PC-5)group,ophiopogonin D+K6PC-5 group,and sham group,with 12 rats in each group. Except for the sham group,MIRI models were constructed by ligating the left anterior descending coronary artery of rats in all other groups. After successful modeling,medication treatment was carried out immediately,once a day for 2 weeks. The ultrasound imaging system was applied to evaluate changes in left ventricular ejection fraction (LVEF) and left ventricular fractional shortening(LVFS)in rats. HE staining was applied to detect the pathology of myocardial tissue. ELISA was applied to detect levels of creatine kinase isoenzyme (CK-MB),lactate dehydrogenase (LDH),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)in myocardial tissue. TUNEL staining was applied to detect myocardial cell apoptosis in myocardial tissue. Immunohistochemical staining was applied to detect the proportions of Bim and Caspase-3 positive cells in myocardial tissue. Western Blot was applied to detect S1P,SphK1,and S1PR1 proteins in myocardial tissue. Results Compared with the sham group,rats in the MIRI group showed myocardial structural damage,disordered fiber arrangement,decreased myocardial cells,nuclear pyknosis,and a large number of inflammatory cell infiltration. The LVFS and LVEF decreased,the levels of CK-MB,LDH,IL-1β,TNF-α,myocardial cell apoptosis rate,proportions of Bim and Caspase-3 positive cells,and S1P,SphK1,and S1PR1 proteins in myocardial tissue were elevated (P<0.05). Compared with the MIRI group,the rats in the ophiopogonin D group showed relief of above-mentioned phenomenon,including myocardial structural damage,disordered fiber arrangement,decreased myocardial cells,nuclear pyknosis,and infiltration of a large number of inflammatory cells. The LVFS and LVEF increased,the levels of CK-MB,LDH,IL-1β,TNF-α,myocardial cell apoptosis rate,proportions of Bim and Caspase-3 positive cells,and S1P,SphK1,and S1PR1 proteins in myocardial tissue decreased (P<0.05). K6PC-5 reversed the effects of ophiopogonin D on cardiac dysfunction,myocarditis,and myocardial cell apoptosis in MIRI rats. Conclusion The mechanism by which ophiopogonin D inhibits myocarditis and myocardial cell apoptosis in MIRI rats may be related to the inhibition of the SphK1/S1P/S1PR1 pathway.
维普
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