双苯氟嗪抑制FasL分子表达的基因转录机制(英文)

Repression of FasL expression by dipfluzine involves a mechanism of inhibition of NFATc transactivation

研究双苯氟嗪对Fas配体分子表达抑制的基因转录机制的影响。通过四血管阻断法建立大鼠全脑缺血再灌注损伤模型,所有实验动物缺血15 min,再灌注72 h。实验大鼠随机分为4组:假手术组、缺血再灌注组、双苯氟嗪组及环孢素A组。药物干预于再灌注后2 h内给药,每日1次,连续3 d。双苯氟嗪按20 mg·kg-1灌胃给药,环孢素A 10 mg·kg-1腹腔注射。应用蛋白质印迹和电泳迁移率改变分析技术检测海马CAI区Fas配体(FasL)、转录因子NFATc、I-κB-α、phospho-I-κB-α蛋白表达以及测定FasL分子启动子远端及FasL分子启动子近端NFATFasL-DNA结合活性。结果表明,双苯氟嗪明显降低FasL、NFATc的蛋白表达并显著减少FasL分子启动子远端及FasL分子启动子近端NFAT结合位点的NFAT-DNA结合活性。各组之间I-κB-α蛋白表达无显著区别。未观察到各组phospho-I-κB-α蛋白表达。由此可见,双苯氟嗪通过降低转录因子NFATc的FasL分子的基因转录功能,从而抑制FasL分子的基因表达。

Previous studies showed that dipfluzine （Dip）, a L-type calcium channel blocker, had neuroproteetive effect on the hippocampal CA1 region neurons subjected to transient forebrain isehemia through inhibiting the Fas ligand （FasL）-induced death signaling transduction pathway. However, the molecular basis of Dip-mediated repression of FasL gene expression was not clear.