中文摘要：

本文研究了丝裂原活化蛋白激酶（mitogen activated protein kinases,MAPKs）信号通路在组蛋白去乙酰化酶抑制剂（histone deacetylase inhibitors,HDACis）曲古抑菌素A（trichostatin A,TSA）抑制间充质干细胞（mesenchymal stem cells,MSCs）C3H10T1/2成脂分化中的调节机制.首先利用MTT法检测TSA对其增殖活性的影响;Western印迹法首先检测MAPKs信号通路中pERK和p-p38蛋白在间充质干细胞C3H10T1/2成脂分化过程中的表达情况,以及不同浓度、不同时间TSA处理对pERK和p-p38蛋白差异变化情况;其次再用Western印迹检测TSA对成脂分化过程中间充质干细胞pERK和p-p38蛋白表达的影响.MTT结果显示,TSA浓度在1 nmol/L～100 nmol/L范围内抑制C3H10T1/2细胞的增殖活性,且TSA浓度约为60 nmol/L时即抑制一半以上的C3H10T1/2细胞增殖活性.Western印迹结果显示,TSA处理5 min～80 min,及浓度在1 nmol/L～100 nmol/L范围内激活MAPK信号通路中pERK和p-p38蛋白的表达;C3H10T1/2细胞成脂分化过程中,胞内pERK和p-p38蛋白的表达呈现下调趋势;而TSA抑制了成脂分化过程中C3H10T1/2细胞内pERK和p-p38蛋白的表达变化.本研究结果提示,在C3H10T1/2细胞成脂分化过程中,MAPK信号途径分子pERK和p-p38表达下调;TSA可能是通过活化pERK和p-p38进而抑制间充质干细胞C3H10T1/2成脂分化.

英文摘要：

This paper was involved in the regulatory mechanism of mitogen activated protein kinases（MAPKs） signaling pathways in the inhibition effect of trichostatin A（TSA） on adipogenic differentiation in mesenchymal stem cells（MSCs）.C3H10T1/2 cells were used as a suitable model for this study.The proliferation of cells treated by TSA was detected by MTT method.Western blotting was first applied to detect the expression of pERK and p-p38 proteins after C3H10T1/2 cells treated with TSA or adipogenic differentiation medium（ADM）,and then to detect the expression of pERK and p-p38 proteins in the adipogenic progress of MSCs after C3H10T1/2 cells treated with TSA.Cells proliferation was inhibited with TSA and inhibition ratio was reached 50% at 60 nmol/L.Western blotting showed that TSA activated pERK and p-p38 proteins in the MAPKs signaling pathways and the expression of pERK and p-p38 proteins were down-regulated in the adipogenic progress.TSA inhibited the expression of pERK and p-p38 proteins in the adipogenic progress were also found in this study.Our results demonstrate that TSA inhibited adipogenic differentiation by activating pERK and p-p38.