| Background and objective: The recently studies demonstrated that many cytokines participated in myocardial ischemia reperfusion injury(l/R). As a potent proinflammatory cytokine, Interleukin (IL)-18 plays a central role in orchestrating the cascade and accelerates atherosclerosis, but it still remains poorly understood in myocardial I/R. In this study we assessed the influence of methylprednisolone on IL-18 and the plasma concentrations of IL-18 in myocardial I/R model in rat. Meanwhile, we examined the relation between plasma concentrations of IL-18 and the clinical instability of coronary artery disease and investigated the plasm concentrations of IL-18 before and after percutaneous transluminal coronary angioplasty(PTCA).Methods:Basic study: All studies were performed on 63 healthy male Wistar rats, which were randomly divided into three groups: sham groud(n=21), I/R groud(n=21) and Mehtylprednisolone group(n=21). Every groups include ischemia 30min subgroud (Isomin, n=7), reperfusion 30min subgroud(l/R30min, n=7) and reperfusion 2h subgroud (l/R2h, n=7). Rats were pretreated by methylprednisolone (30mg/kg, methylprednisolone group) or saline (0.75ml/kg, sham and control groud) before ischemia. Plasma IL-18, CK-MB(creatine phosphokinase-KB), myocardium myeloperoxidase (MPO) weremeasured and myocardia infarct size were analysis at respective time points.Clinical study: We studied 31 patients with coronary heart disease (CHD) (20 male) admitted in hospital and 5 healthy persons. Patients were classified as stable angina pectoris group(n=18), unstable angina pectoris group(n=13) and control group(n=5). All patients were performed coronary angiography and plasma concentrations of IL-18 were measured. In stable angina pectoris group, 11 patients were performed PTCA. Plasma concentration of IL-18 were measured before and after PTCA.Result:Basic study: Serum concentration of CK-MB started to increase gradually (p<0.05) , and was significantly increased at 2 hours after reperfusion (p<0.01) , while IL-18 was significantly increased at 2 hours after reperfusion (p<0.01) . Meantime myocardial MPO was also significantly increased gradually at 30min after ischemia. In the methylprednisolone treated group, the increase of CKMB, MPO and IL-18 were delayed and the level were significantly lower than those of ischemia and reperfusion group at 2 hours after reperfusion (p<0.05) . In addition, the expression of IL-18 positively correlated with CKMB and MPO. (p<0.01) .Clinical study: Plasma concentrations of IL-18 are not significant difference in patients with stable angina pectoris and healthy persons, but they are significantly increased in patients with unstable angina pectoris(p<0.01). Plasma concentrations of IL-18are correlated with LDL and left ventricular ejection fraction. In PTCA group, plasma concentrations of IL-18 were significantly increased after PTCA and the elevation of IL-18 were correlated well with the extent of ischemia.Conclusion: 1.During myocardial ischemia/reperfusion, IL-18 was produced and increased gradually.2. Methylprednisolone can inhibit the product of IL-18 in myocardial ischemia/reperfusion and this perhaps is one of its mechanism reducing the myocardial inflammatory injury.3. Plasma concentrations of IL-18 were significantly increased after PTCA and were correlated well with the extent of ischemia.4.IL-18 is not only a marker of inflammatory in atherosclerosis, but also a sensitive marker of the early inflammatory response after PTCA.
|
PDF Full Text Request