4-甲基伞形酮对瘢痕疙瘩成纤维细胞的抗炎作用及机制研究

The Study on Anti-inflammatory Effect and Mechanisms of 4-methylumbelliferone in Keloid Fibroblasts

目的:探讨4-甲基伞形酮(4-methylumbelliferone,4MU)对瘢痕疙瘩成纤维细胞的作用及机制研究。方法:体外培养的原代瘢痕疙瘩成纤维细胞(KFs)分别用浓度为0、0.2、0.4、0.8mM的4MU处理,采用CCK-8法和细胞划痕实验检测4MU对KFs细胞增殖和迁移能力的影响,通过ELISA、qPCR、免疫荧光染色和Western-bloting技术检测4MU对KFs炎症相关因子表达的影响。结果:4MU不仅抑制KFs细胞增殖迁移,而且可减少KFs对IL-6和IL-8的分泌,同时抑制HAS2和HAS3 mRNA的表达及α-SMA、TLR4、CD44、NF-κB1、P65蛋白的合成。结论:4MU可以抑制KFs增殖和迁移,并可通过抑制NF-κB通路相关基因的表达,减少KFs炎症因子分泌,因此,4MU有可能成为治疗瘢痕疙瘩的新药物。

Objective To investigate the effect of 4-methylumbelliferone(4MU)on keloid fibroblasts(KFs).Methods Primary keloid fibroblasts were respectively treated with 4MU at concentrations of 0,0.2,0.4,and 0.8 mM.The proliferation and migration ability of KFs were detected by CCK-8 assay and cell migration assay.ELISA,qPCR,immunofluorescence and Western-bloting techniques were applied to study the effects of 4MU on the expression of inflammation-related genes in KFs.Results 4MU not only inhibited the proliferation and migration of KFs,but also inhibited the secretion of IL-6 and IL-8.Additionally,4MU inhibited the expression of HAS2 and HAS3,and reduced the synthesis ofα-SMA,TLR4,CD44,NF-κB1 and P65 proteins in KFs.Conclusion 4MU treatment can not only inhibit the activity of KFs,but also decrease the secretion of inflammatory by downregulating the expression of NF-κB signal pathway.Therefore,4MU has the potential to be a new drug for the cure of keloids.