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目的 研究普罗布考对2型糖尿病患者外周血单核细胞Toll样受体4/核因子kB信号转导通路的影响,以进一步探讨普罗布考抗动脉粥样硬化机制.方法 选择85例2型糖尿病合并冠心病患者,随机分为对照组和治疗组:对照组按常规治疗,治疗组在常规治疗基础上加用普罗布考0.375 g,每天2次,口服,总疗程为24周.运用Real-time PCR、Western blotting方法分别测定治疗前后外周血单核细胞Toll样受体4、核因子kB mRNA和蛋白表达水平;ELISA检测外周血血清中白细胞介素1β的表达水平.结果 普罗布考显著降低2型糖尿病合并冠心痛患者总胆固醇、甘油三酯、低密度脂蛋白胆固醇和氧化型低密度脂蛋白水平,显著下调外周血单核细胞Toll样受体4 mRNA和蛋白的表达(P<0.05),明显减少核因子kB蛋白的表达,且显著抑制白细胞介素1β的生成(P<0.05).结论 普罗布考抗动脉粥样硬化除了降脂作用外,抑制外周血单核细胞Toll样受体4/核因子kB信号转导通路的激活,也可能是其抗炎、抗动脉粥样硬化的重要机制之一,提示普罗布考对防治2型糖尿病并发动脉粥样硬化这类患者有一定的作用.“,”Aim To study the influence of probucol on the Toll-like receptor 4 (TLR4)/nuclear factor-kB (NF-kB) signaling pathway of peripheral blood mononuclear cells in type 2 diabetic mellitus patients with coronary heart dis-ease, so as to further investigate the anti-atherosclerosis mechanism of probucol. Methods 85 patients with type 2 di-abetes and carotid atherosclerosis were divided into two groups : probucol treatment group (n = 43), and control group (n = 42). The treatment group were treated with probucol 0. 375 g, 2 times a day for 24 weeks. The effect of probucol on TLR4, NF-kB expression of peripheral blood monouclear cells was detected by Real-time PCR and Western blotting analy-sis before and after probucol treatment. The expression of interleukin-1β (IL-β) was detected by ELISA. Results Probucol obviously decreased levels of total cholesterol (TC), triglyceride (TG), low density iipoprotein cholesterol (LD-LC) and oxidized low density lipoprotein (ox-LDL) in plasma of type 2 diabetes. The expressions of TLR4, NF-kB and IL-β of peripheral blood mononuclear cells were significantly lower in probucol treatment group than that in control (P < 0.05). Conclusions Probucol can not only regulate serum lipids, but also has the action of anti-atherosclerosis through inhibiting TLR4/NF-kB expression, which indicate that probucol might have the preventive and treatment role in patients with type 2 diabetes and atherosclerosis.