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目的：探讨Toll样受体4（TLR4）在溶血磷脂酸诱导的平滑肌细胞表型转化中的作用。方法建立原代培养的大鼠主动脉平滑肌细胞（ RASMC）模型，分别用3种TLR4特异性小干扰RNA（ siRNA）转染大鼠平滑肌细胞后，经过筛选TLR4－siRNA－2成为最佳RNA干扰序列。用1μmol? L－1溶血磷脂酸处理空白对照组、RASMC组、RASMC＋阴性对照siRNA组、RASMC＋TLR4－siRNA－2转染组4 h，镜下观察各组形态，用RT－PCR、Western法检测SMA－α及骨桥蛋白基因的表达。再用乙酰胆碱分别刺激上述溶血磷脂酸处理的各组RASMC，观察细胞形态变化并照相、用 RT －PCR 法检测 SMA －α及骨桥蛋白的表达。结果溶血磷脂酸诱导RASMC细胞骨桥蛋白基因的上调及SMA－α基因的下调，TLR4－siRNA转染细胞后可显著抑制溶血磷脂酸诱导的RASMC细胞骨桥蛋白基因上调及SMA－α基因下调，但对于RASMC细胞形态没有影响，部分抑制溶血磷脂酸诱导的RASMC细胞表型转化。结论溶血磷脂酸可能部分通过TLR4信号途径，促进细胞表型的转化，阻断TLR4受体，抑制信号通路后的炎症反应及免疫反应，有可能成为干预动脉粥样硬化潜在途径。“,”Objective To investigate the effects of special siRNA target-ting toll like receptor 4 ( TLR4) gene( TLR4-siRNA) on LPA-stimu-lated phenotypic modulation of vascular smooth muscle cells.Methods depressed by TLR4 -siRNA transfection, which held back the down -regulation of SMA -αgene expression, de-pressed up-regulation of osteopontin gene expression induced by lysophosphatidic acid, but there were no cell shape changes as compared with dedifferentiated RASMCs.Conclusion LPA-stimulated phenotypic modulation of VSMC may partly involve TLR4 pathway.Inhibition of inflammatory and immunity reaction might be a potential novel target for therapeutic intervention for arteriosclerosis.