雷公藤内酯醇通过细胞凋亡阻止人T细胞增殖

TRIPTOLIDE INDUCES GROWTH ARREST OF HUMAN T CELLS THROUGH ITS APOPTOTIC EFFECT

目的：通过观察雷公藤内酯醇是否能导致人外周血Ｔ细胞发生细胞凋亡（ａｐｏｐｔｏｓｉｓ），探讨该化合物阻止淋巴细胞增殖的作用机理。方法：选择被ＰＨＡＰ，佛波脂（ＰＭＡ），及白介素２（ＩＬ２）等有丝分裂原刺激的人Ｔ细胞为研究对象，以吖啶橙染色细胞的形态，ＤＮＡ片断的测定，和ＤＮＡ凝胶电泳作为判断细胞出现细胞凋亡的标准。结果：①未发现雷公藤内酯醇能使处于静止状态的Ｔ细胞出现细胞凋亡；②雷公藤内酯醇与有丝分裂原同时作用于Ｔ细胞后，其３ＨＴｄＲ掺入率明显降低的同时，只有少量的Ｔ细胞呈细胞凋亡的表现，ＤＮＡ片断检测也无显著变化；③对已活化的Ｔ细胞，雷公藤内酯醇可使大量Ｔ细胞呈细胞凋亡样变化，此时其ＤＮＡ片断的测定和ＤＮＡ凝胶电泳均证实活化的Ｔ细胞已发生了细胞凋亡；而且，作者还证实活化的Ｔ细胞细胞凋亡的发生与雷公藤内酯醇呈浓度依赖性。活化的Ｔ细胞３ＨＴｄＲ掺入明显减少。

OBJECTIVE Triptolide is a potent immunosuppressive ingredient of diterpenoid from Tripterygium Wilfordii Hook f.(TWHf). In this study, the mechanism by which triptolide exerts the suppressive effect on arrested T lymphocytes was investigated. METHODOLOGY Human peripheral T cells stimulated by mitogen were treated with or without triptolide at different concentrations. Apoptosis of T cells were evaluated and qualified by AO staining and DNA fragmentation assay. Cell proliferation was detected by 3H TdR incorporation. RESULTS Triptolide was found to be able to induce apoptosis in mitogen stimulated active T cells, and arrested growth of these T cells was observed. This effect of triptolide was dose dependent. In addition, there was no evidence for the suppressive effect of triptolide on the proliferation and apoptosis of resting T cell. CONCLUSION The apoptotic effect of triptolide may account for the immunosuppressive action of TWHf.