Abstract: Objective To investigate how the infection factors affect the activation and biologic function of dermal fibroblasts by regulating the activation phenotype of macrophages. Methods The activation phenotype of macrophages was assessed by flow cytometry ；the interaction between macrophages and fibroblasts was established by a transwell co- culture system ；the proliferation of dermal fibroblasts was determined by MTT assay；the expression of α-SMA in fibroblasts was detected by cell immunofluorescence；the secretion of type Ⅰ and type Ⅲ collagen was detected by ELISA；the mRNA expression of MMP9 and MM913 was detected by q-PCR. Results The M2 macrophages activated by IL-4 could significantly induced the expression of α-SMA，promoted the proliferation and secretion of type Ⅰ and type Ⅲ collagen of dermal fibroblasts. However，LPS could significantly induce macrophages activating to M1 phenotype and macrophages activated by LPS could dramatically inhibit the secretion of type Ⅰ and type Ⅲ collagen of dermal fibroblasts and promote the expression of MMP9 and MMP13. Conclusion Infection factors could affect the activation and biological function of dermal fibroblasts by regulating the activation phenotype of macrophages. We expected that people could improve wound healing by regulating the activated phenotype of macrophages in the wound area in the future.

Key words: macrophage, infection, fibroblast, wound healing

摘要： 目的 观察感染因素（细菌脂多糖，LPS）如何通过调控巨噬细胞表型变化影响皮肤成纤维细胞的活化状态和功能。方法 运用流式细胞技术检测巨噬细胞的活化表型；应用transwell共培养体系建立巨噬细胞和成纤维细胞共培养的模型；用MTT实验检测成纤维细胞的增殖情况；用细胞免疫荧光技术检测成纤维细胞α-SMA的表达；用ELISA实验检测细胞培养上清中Ⅰ型、Ⅲ型胶原蛋白的分泌；用q-PCR检测成纤维细胞中MMP9，MMP13的mRNA表达情况。结果IL4诱导的M2型激活的巨噬细胞能够显著诱导皮肤成纤维细胞（HFF）高表达活化标志物α-SMA，促进成纤维细胞增殖并分泌大量Ⅰ型及Ⅲ型胶原蛋白。而感染因素LPS则能显著诱导巨噬细胞向M1表型活化，而这种活化的巨噬细胞与成纤维细胞共培养能显著抑制成纤维细胞胶原蛋白的分泌并促进基质金属蛋白酶的表达。结论 感染因素能够通过调控巨噬细胞表型影响成纤维细胞的活化和功能，调控巨噬细胞的活化表型有望改善伤口愈合不良。

关键词: 巨噬细胞, 成纤维细胞, 感染, 伤口愈合