中文摘要：

增生性瘢痕是机体在创伤后过度修复的表现形式之一，其发病机制并不十分明确．最近有证据显示，成纤维细胞能在脂多糖（1ipopolysaccharide，LPS）的作用下，激活toll样受体4（toll like receptor-4，TLR-4），参与调节免疫／炎症反应．因此，探索了TLR-4在增生性瘢痕的产生中可能起到的作用．利用荧光定量PCR检测证实，在体外培养的原代增生性瘢痕成纤维细胞（hyperplastic scar fibroblast，HSFB）中TLR－4和骨髓分化因子88（myeloid differentiation factor88，MyD88）的表达高于正常皮肤成纤维细胞（normal skin fibroblast，NFB）．用LPS处理NFB和HSFB24h，发现TLR-4、MyD88和转化生长因子B1（transforming growth factor-beta，TGF-β1）、I型前胶原在mRNA和蛋白质水平的表达均上调．MTT也证实LPS促进体外培养的HSFB的增殖效应强于NFB．然而，在HSFB中采用siRNA干扰MyD88后，再用LPS处理，与干扰对照组相比，MyD88、TGF-β1和I型前胶原的表达均明显减弱．结果表明，在皮肤成纤维细胞激活TLR-4信号通路，能引起促炎细胞因子TGF-β1的产生，同时促进细胞增殖，而干扰MyD88，能抑制LPS刺激后这些细胞因子的表达．

英文摘要：

Hyperplastic scar, a fibroproliferative disorder, complicates wound healing. Although the pathogenesis is not well understood, prolonged inflammation is a known contributing factor. Emerging evidence suggests that fibroblasts regulate immune/inflammatory responses through toll-like receptor 4 （TLR-4） activated by lipopolysaccharide （LPS）, leading to nuclear factor-KB （NF-KB） and mitogen-activated protein kinases （MAPK） activation, cytokine gene transcription and co-stimulatory molecule expression and resulting in inflammation. So the possible roles of TLR-4 in hyperplastic scar formation need to be explored. Paired normal and hyperplastic scar tissue was collected and dermal fibroblasts isolated and cultured. Quantitative RT-PCR of pairs of fibroblasts demonstrated mRNA levels for TLR4 and its legend myeloid differentiation factor 88 （MyD88） in hyperplastic scar fibroblasts （HSFB） were increased significantly compared with normal fibroblasts （NFB）. When paired normal and HSFB were stimulated with LPS, significant increases in mRNA and protein levels for TLR-4, MyD88, transforming growth factor-betal （TGF-β1） and I procollagen were detected. However, when transfected with MyD88 small interfering RNA （siRNA） in HSFB, then stimulated with LPS, a significant decrease in mRNA and protein levels for these molecules compared to only LPS-stimulated fibroblasts was detected. In comparison, a scramble siRNA transfection did not affect mRNA or protein levels for these molecules. Results demonstrate LPS stimulates proinflammatory cytokine expression in dermal fibroblasts and MyD88 siRNA eliminates the expression. Therefore, controlling inflammation and manipulating TLR signaling in skin cells may result in novel treatment strategies for hyperplastic scar.