阿托伐他汀对大鼠急性心肌缺血再灌注无复流现象的影响及其机制

Effects and mechanism of atorvastatin on no-reflow phenomenon after acute myocardial ischemia-reperfusion in rats

目的探讨阿托伐他汀预处理对大鼠急性心肌缺血再灌注后无复流现象和前炎症因子白介素17(IL-17)表达的影响、相关机制及IL-17在其中的作用。方法健康雄性Wistar大鼠18只,按体质量从大到小排序,然后采用随机数字表法将大鼠分成3组:假手术组、损伤组、预处理组,每组6只。预处理组给予阿托伐他汀2mg·kg^(-1)·d^(-1),另外两组给予等量生理盐水,每天1次,共7 d。损伤组和预处理组予冠状动脉结扎60 min、再灌注15min,建立大鼠急性心肌缺血再灌注模型,假手术组只穿线不结扎。大鼠冠状动脉结扎前,结扎后15、30min和45min、再灌注15min时查心电图。再灌注15min后取血及心脏。形态学方法观察建模后是否存在无复流现象以及他汀类药物对无复流现象的影响。用酶联免疫吸附法(ELISA)测血清IL-17、IL-6水平。结果大鼠急性心肌缺血再灌注后存在无复流现象。与损伤组相比,预处理组无复流面积明显减小[(21.37%±3.35%)比(48.96%±6.94%),P<0.01],血清IL-17[(90.45±11.63)ng/L比(151.67±11.19)ng/L,P<0.05]和IL-6[(112.47±10.40)ng/L比(167.89±5.13)ng/L,P<0.05]显著降低。结论他汀类药物可减少无复流心肌范围,并且可减轻IL-17和炎症因子IL-6的表达,这可能是其减轻炎症、减少大鼠急性心肌缺血再灌注后无复流的机制之一。

Objective To evaluate the effects and mechanism of atorvastatin on no-reflow phenomenon and expression of serum interleukin-17 （IL-17）. Methods Eighteen healthy male Wistar rats were randomly divided into 3 groups： sham operation group （ n = 6） , injury group （ n = 6） and preconditioning of atorvastatin group （ n = 6）. The preconditioning group was given atorvastatin （2 mg·kg-1· d-1 ） and other two groups were given the same volume of saline for 7 days. Twenty-four hours after the last administration, acute myocardial ischemia-reperfusion model was established by ligating the left anterior descending coronary artery for 60 minutes then opening for 15 minutes in injury and preconditioning group. Morphological method was used to observe whether no-reflow phenomenon existed after acute myocardial ischemiareperfusion. Serum level of IL-17 and IL-6 was detected by ELISA. Results No-rellow phenomenon existed after acute myocardial ischemla-reperfusion. Compared with injury group, no-reflow area was significantly reduced in preconditioning group [（21.37% ± 3.35% ） vs. （48.96%± 6.94% ）, P 〈 0. 01 ]. Serum level of IL-17 [（90. 45 ± 11.63 ） ng/L vs. （151.67 ±11.19） ng/L,P 〈0.05] and lL-6 [（ 112.47 ± 10.40） ng/L vs. （167.89±5.13） ng/L,P 〈0.05] were significantly lower in preconditioning group than in injury group. Conclusions Atorvastatin can inhibit the expressions of 1L-17 and IL-6 and reduce no-reflow area in rat acute myocardial ischemia-reperfusion model.