Role of interelenkin-17, -6 and endothelin-1 in statins attenuated no-reflow phenomenon of rat acute myocardial infarction and reperfusion

Abstract

Objective To study the relevant effect of proinflammatory cytokines interelenkin-17(IL-17), -6 and endothelin-1 (ET-1) on statins attenuating no-reflow phenomenon after myocardial ischemia-reperfusion in rats.Methods Eighteen healthy male Wistar rats were randomly divided into 3 groups according to body weight: sham operation, injury, preconditioning groups. The preconditioning group was given atorvastatin 2 mg·kg-1 ·d-1 and the other two groups were given the same volume of saline once. After 7 days, the rats were anesthetized with an intraperitoneal injection of chloral hydrate, and then the thoracic cavity was opened. The coronary artery of injury group and preconditioning group were ligated for 60 minutes, and then opened for 15 minutes, to establish the rat acute myocardial ischemia-reperfusion model. The sham operation group was was treated with a seam through the coronary artery without ligation. Eleetrocardiogram was checked before ligation, and ligation was carried out for 15, 30, 45 minutes and then reperfusion for 15 minutes. After reperfusion for 15 minutes, the thioflavine S and Even's were injected from femoral venous, then the heart and blood were obtained(keeping left ventricular only). Hearts were flushed with saline and sliced transversely into five to seven sections. Finally, observed at 365 nm wave length the existence of non-fluorescent areas, which was no-reflow zone. The level of serum IL-17, IL-6 and ET-1 was detected by ELISA. Results The electrocardiogram confirmed that the sham operation group had no ischemic damage and the model of myocardial ischemia- reperfusion was established in preconditioning group and injury group. The noreflow phenomenon could be observed under 365 nm wave length in preconditioning group and injury group. The ligated area[LA％, (57.34 ± 11.49)％, (53.08 ± 8.66)％] of injury group and preconditioning group was higher than that of sham operation group(0, all P ＜ 0.05); the area of no-reflow[ANF％, (48.96 ± 6.94)％, (21.37 ±3.35)％] of injury group and preconditioning group was higher than that of sham operation group(0, all P ＜ 0.05),and the ANF％ of preconditioning group was lower than that of injury group(P ＜ 0.05) ; the level of serum IL-17,IL-6 and ET-1[(151.67 ± 11.19) × 10-9, (167.89 ± 5.13) × 10-9, (322.37 ± 19.08) × 10-9 g/L] of injury group was higher than those of sham group and preconditioning operation group[(49.75 ± 14.06) × 10-9, (59.32 ± 5.26) ×10-9, (109.9 ± 12.12) × 10-9, (90.45 ± 11.63) × 10-9, (112.47 ± 10.40) × 10-9 and(198.91 ± 27.88) × 10-9 g/L,P ＜ 0.05], the level of serum IL-17, IL-6 and ET-1 of preconditioning group was higher than those of sham operation group(P＜ 0.05). Conclusions no-reflow phenomenon is related with IL-17 and ET-1 which can promote the expression of IL-6, statins decreases the expression of IL-17 and ET-1, and then decreases the on-reflow phenomenon. Key words: Interleukins; Endothelins; Reperfusion injury; Cystatins