白介素-18促动脉粥样硬化斑块内细胞凋亡的作用

The role of Interleukin-18 in promoting apoptosis of cells in atherosclerotic plaques

目的探索白介素-18(IL-18)促进动脉粥样硬化斑块内细胞凋亡的作用及其机制。方法采用30只老年同龄雄性动脉粥样硬化模型新西兰大白兔制成60个动脉粥样硬化板块标本,采用析因设计,给予IL-18进行刺激,以不同的IL-18刺激时间和刺激浓度组合作为新处理组,将60个动脉粥样硬化斑块标本随机分入新处理组中(n=5),测量在不同刺激时间和刺激浓度下,纤维帽的厚度与脂核横截面厚度的变化,TUNEL法检测斑块内细胞凋亡的改变。结果帽/核比值与斑块内细胞凋亡指数随着IL-18的浓度及刺激天数的改变而变化(P<0.01)。帽/核比值随着IL-18的浓度及刺激天数增加而降低(P<0.01),斑块内细胞凋亡指数随着IL-18的浓度及刺激天数增加而升高(P<0.01);斑块内细胞的凋亡指数与帽/核比值呈显著线性负相关(r=-0.776,P<0.001)。结论 IL-18诱导斑块内细胞凋亡可能是其促易损斑块形成的重要机制。

Objective To explore the role and mechanism of interleukin-18（IL-18） in promoting apoptosis of cells in atherosclerotic plaques.Methods 30 male New Zealand white rabbits were selected and euthanized.The entire length of the aorta was exposed and divided into several segments.Histological assessment of experimental atherosclerosis was evaluated.Rabbits in experimental group were received stimulation of IL-18.New group was established according to work time and concentration of IL-18,the 60 specimens were randomly divided into the new treatment group（n= 5）,the thickness of fibrous cap and nuclear cross section were measured after stimulation of IL-18.At last,apoptosis was detected by TUNEL.Results The cap/core ratio and apoptotic index of plaques were changed according to the concentration and work time of IL-18｜（P〈0.01）,with the concentration and work time of IL-18 increased,the cap/core ratio of plaques reduced（P〈0.01） and apoptotic index of plaques raised inversely（P〈0.01）,apoptotic index of cell in plaques was significantly negatively correlated with the cap/core ratio（r=-0.776,P〈0.001）.Conclusions IL-18 inducing apoptosis in plaque may be the main mechanisms of promoting the formation of vulnerable plaque.