探讨白介素18结合蛋白对球囊损伤后内膜增殖的影响及其机制

Effect of interleukin18 binding protein on neointimal proliferation after balloon injury and its possible mechanism

目的:观察白介素18结合蛋白(Interleukin 18 binding protein,IL-18BP)对高脂饮食兔髂总动脉球囊损伤后动脉内膜增殖的影响,并探讨可能的机制。方法:将48只雄性新西兰大白兔随机分为4组:对照组、模型组、低剂量治疗组和高剂量治疗组,高脂饮食3周后行球囊损伤术。术时低剂量及高剂量组在夹闭近端髂总动脉之前分别给予5、10μg IL-18BP快速耳缘静脉注射,对照组与模型组给予等体积的生理盐水静脉注射。术后继续高脂饮食,分别在球囊损伤后2周和4周将兔处死,最终共有43只雄性新西兰大白兔纳入实验。取髂总动脉,行HE染色,观察髂总动脉病理变化及内膜增殖情况,免疫组织化学染色检测核因子κB(Nuclear factor kappa B,NF-κB)在血管内膜中的表达,Western blot检测NF-κB蛋白的半定量表达。结果:模型组动脉血管内膜明显增生,内膜下和中膜可见大量泡沫细胞堆积,有明显的粥样硬化斑块形成;与模型组相比,治疗组均有内膜增厚明显减轻,内膜下有少量泡沫细胞形成(P<0.05);免疫组化和Western blot结果显示治疗组NF-κB阳性表达率均明显低于模型组(P<0.01)。结论:IL-18BP可明显抑制血管内膜过度增生,其机制可能与其抑制血管内膜NF-κB表达,从而减轻炎症反应有关。

Objective：To investigate the effect and mechanism of interleukin 18 binding protein（IL-18BP） on neointimal proliferation of rabbit common iliac artery after balloon injury.Methods： New Zealand white male rabbits（n=48）were randomly divided into four groups：the control group,model group,low-dose treatment group and high-dose treatment group.All the rabbits were fed with hypercholesterol diet for 3 weeks,then IL-18BP was given to the rabbits in low-dose treatment group（5 μg） and high-dose treatment group（10 μg） by intravenous bolus injection during surgery,while the other two groups were treated with saline at the same volume.The rabbits were killed at 2 weeks and 4 weeks after balloon-injury.A total of 43 rabbits were used for this study.The common iliac artery was assayed by hematoxylin and eosin（HE） staining to investigate artery morphology and the thickness of arterial intima and media;the location and quantity of nuclear factor kappa B（NF-κB） were detected by immunohistochemistry and Western blot.Results： Compared with the control group,foam cells and intimal thickness in the model group were significantly increased;and those in low-dose treatment group and high-dose treatment group were decreased compared with the model group（P0.05）;compared with model group,the expression of NF-κB in low-dose and high-dose group was reduced significantly（P0.01）.Conclusion： IL-18BP can significantly decrease arterial neointimal hyperplasia after balloon-injury and the mechanism may be related to its inhibition of the expression of NF-κB.