依曲替酸(R_O10-1670)对培养的正常人角质形成细胞Fas/Fasl系统表达及凋亡的研究

目的　通过研究依曲替酸作用于培养的正常人KC前后Fas/Fasl的表达及其与凋亡的关系 ,进一步探讨其治疗银屑病的作用机理。方法　依曲替酸作用培养的正常人KC后 ,进行免疫细胞化学研究 ,观察其对KC表达Fas/Fasl蛋白的影响。用流式细胞仪 (FACS)对依曲替酸处理后的KC进行凋亡检测。结果　①正常人KC几乎不表达Fas和Fasl ;②依曲替酸作用 16h时KC的Fasl表达最强 ,40h时表达Fas最强 ;相同条件下 ,KC表达Fasl比Fas弱 ;③依曲替酸刺激后引起KC凋亡。结论　培养的正常人KC中Fas/Fasl系统不参与其凋亡 ;依曲替酸作用于培养的正常人KC后 ,上调Fas/Fasl系统表达 ,并促进KC凋亡 ,拮抗KC良性增生 ,Fas/Fasl介导的凋亡可能是维甲酸治疗银屑病的重要原因。

Investigation of the Effect of Etretin on the Expression of Fas/Fasl Ligand and Apoptosis in Cultured Human Keratinocytes

Objective To illuminate a possible mechanism of Fas/Fasl in the treatment of psoriasis,the expression of it and apoptosis of KC were investigated.Methods With cell culture,immunocytochemistry,the expression of Fas/Fasl protein after the treatment with etretin were observed in cultured human normal keratinocytes.Then,the state of apoptosis in cultured keratinocyte after stimulation with etretin was detected with FACS.Results ①There was no expression of Fas/Fasl protein in the cultured normal human KC.②After the treatment with etretin, the strongest expression of Fasl protein appeared after 16h,so did Fas after 40h.Under the same conditions,the expression of Fas was stronger than that of Fasl.③Keratinocytes' apoptosis occurred after stimulation with etretin.Conclusion Fas/Fasl system isn't involved in apoptosis in cultured human normol keratinocytes.But during limited period,the apoptosis of KC could be induced by etretin,thus it can antagonize benign hyperplasia of keratinocytes.Our data showed up-regulation of the expression of Fas/Fasl system and apoptosis in cultured human keratinocytes stimulated by etretin,and its function was involved in the therapeutic machanism of psoriasis.