动脉粥样硬化中Toll样受体3上调β型干扰素的表达

摘要

目的 观察动脉粥样硬化病变中Toll样受体3(TLR3)与β型干扰素(IFN-β)表达的关系及影响.方法 下肢动脉硬化性闭塞症(ASO)患者20例,健康对照组20例,通过流式细胞术检测外周血单核细胞TLR3及IFN-β的表达.高脂饮食喂养ApoE(-/-)小鼠,实验组使用聚肌胞苷酸Poly(I:C)腹腔注射,对照组注射等剂量生理盐水.两日注射一次,经10周后,生化分析仪检测血浆中低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、三酰甘油、总胆固醇、葡萄糖(Glu)水平,ELISA法检测血浆及动脉中TLR3、干扰素调节因子3(IRF3)、IFN-β及白介素-1β(IL-1β)水平.结果 下肢ASO患者外周血单核细胞TLR3及IFN-β在ASO组的表达阳性率均显著高于对照组;ApoE(-/-)小鼠中,实验组血浆中Glu水平较对照组显著降低;实验组血浆及动脉中TLR3、IRF3、IFN-β水平较对照组显著增加,IL-1β水平较对照组显著降低.结论 动脉粥样硬化病变中TLR3表达的增加诱导IFN-β,并通过下调IL-1β水平达到抗动脉粥样硬化的作用.%Objective To investigate the relationship and influence of Toll-like receptor 3 (TLR3) and interferon-β(IFN-β) expression in atherosclerotic lesions.Methods In human subject,40 subjects were enrolled.All subjects were divided into two groups:patients with arteriosclerosis obliterans(ASO) (n =20),control group(n =20).The positive rates of TLR3 and IFN-β in human peripheral blood monocytes were measured by flow cytometry.ApoE(-/-) mice were fed in high-fat diet.The mice in experimental group were injected intraperitoneal(ip) by Poly (I:C),The mice in control group were injected ip by normal saline.Every dose was injected once every two days for 10 weeks.Levels of high-density lipoprotein-cholesterol (HDL-C),low-density lipoprotein-cholesterol (LDL-C),triglyceride (TG),total cholesterol(TC),glucose (Glu) in plasma were tested by biochemical analyzer.Levels of TLR3,IRF3,IFN-β and interleukin-1β(IL-1β) in plasma and aorta were tested by ELISA method.Results The expression rates of TLR3 and IFN-β in ASO group were significantly higher than those in control group.In ApoE(-/-) mice,level of Glu in plasma in experimental group was significantly lower than that in control group,level of TLR3,IRF3,IFN-β in plasma and aorta in experimental group were significantly higher than those in control group,level of IL-1β in plasma and aorta in experimental group was significantly lower than that in control group.Conclusion The increased expression of TLR3 in as induced expression of IFN-β,which achieved the role of antiarteriosclerosis by down-regulating the level of IL-1β.