摘要
目的:研究他克莫司和罗格列酮单独或联合应用对肿瘤坏死因子(TNF)-α诱导的HaCaT细胞细胞周期变化的影响,并初步探讨其机制。方法:体外培养HaCaT细胞,经TNF-α诱导,他克莫司、罗格列酮单独以及联合作用后,流式细胞术检测细胞周期变化;Western blot检测细胞周期蛋白(cyclin)D1、P21的表达。结果:TNF-α诱导后HaCaT细胞G_0～G_1期的细胞比例明显降低(37.91±0.72)%,他克莫司和罗格列酮单独或联合应用可增加停滞在G_0～G_1期的细胞比例,其中联合组的G_0～G_1期的细胞比例分别为(46.47+0.43)%、(48.39±0.71)%,较相应单药组(39.62+0.07)%、(40.99±1.05)%明显升高(P<0.05)。他克莫司和罗格列酮单独或联合应用均可致HaCaT细胞cyclin D1表达下调,P21表达上调,其中他克莫司和罗格列酮联合用药组效应显著高于相应单独用药组,差异有统计学意义(P<0.05)。结论:他克莫司和罗格列酮单独或联合应用可以有效阻滞TNF-α诱导的HaCaT细胞细胞周期进程,且联合用药作用更强,该作用可能与cyclin D1、P21的表达改变有关。
Objective： To study the effect of tacrolimus and rosiglitazone on HaCat cell cycle induced by TNF-alpha and its mechanism. Methods： HaCat cell cycle was induced by TNF-cc The changes of cell cycle were assessed by flow cytometry and cell cycle-related proteins were measured by Western blot after treatment with tacrolimus or rosiglitazone alone, or their combination. Results： Following TNF-α treatment, the percentage of HaCat Cells in G0-G1 phase was significantly decreased （37.91±0.72）%. However,either tacrolimus or rosiglitazone alone, or their combination increased the percentage of HaCat Cells in G0-G1 phase. The percentage of HaCat Cells in G0-G1 phase was significantly higher in combination （46.47±0.43）% than in single agent treatment（39.62±0.07）% and （40.99±1.05）%, （P〈 0.05 vs. combination）. In addition, either tacrolimus or rosigli- tazone alone, or their combination was down regulated cyclin D1 and up regulated P21 expression. This effect was more evi- dent in the combination of tacrolimus and rosiglitazone （P 〈 0.05 for combination vs. single agent）. Conclusion： Tacrolimus and rosiglitazone can suppress TNF-α-induced cell cycle changes and combination of tacrolimus and rosiglitazone has a syn- ergic effect. This may be due to down regulation of cyclin DI and up regulation of P21 expression.
出处
《临床皮肤科杂志》
CAS
CSCD
北大核心
2013年第2期69-71,共3页
Journal of Clinical Dermatology
基金
中华医学会皮肤性病学分会-安斯泰来制药(中国)有限公司皮肤病学研究基金(2010年度)资助项目
