还原型辅酶Ⅰ(NADH)对PC12细胞鱼藤酮损伤的分子调控

为探讨NADH对PC12细胞线粒体鱼藤酮损伤的修复机制，采用细胞毒实验、免疫荧光和流式细胞仪检测细胞在鱼藤酮损伤前后细胞增殖基因（c-myc、c-erbB-2）、抗凋亡基因（bcl－2）、抑癌基因（p53）、细胞快反应基因（c-fos）相关蛋白和细胞增殖核抗原（PCNA）的表达。结果表明，鱼藤酮能明显抑制PC12细胞增殖，下调c-erbB-2、c-myc、bcl-2和p53基因的表达；NADH可以抑制鱼藤酮对PC12细胞线粒体的毒性作用，上调细胞bcl-2c、c-myc、c-erbB－2基因和PCR的表达，提示鱼藤酮可能通过控线粒体磷酸化过程和下调细胞增殖基因（c-rebB-2、c－myc）、抗凋亡基因（bcl-2），上调快反应基因(c-fos）表达致使细胞损伤，NADH抑制鱼藤酮对PC12细胞的损伤可能与bcl-2、c-myc、c-erbB-2和p53表达调控有关。

EFFECTS OF REDUCED COENZYME Ⅰ ON REGULATION OF GENE EXPRESSION IN PC12 CELLS DAMAGED BY ROTENONE

To elucidate the mechanism of mitochondrial damage induced by rotenone and the possible biological function of NADH in repairing mitochondrial damage of PC12 cells, cytotoxicity test, immunocytofluorescence and flow cytometric analysis were used to investigate the changes of cell proliferation genes (c myc, c erbB 2), apoptosis inhibition genes bcl 2, p53 tumor suppressor protein, cell immediate early gene (c fos) and proliferating cell nuclear antigen (PCNA) in PC12 cells before and after exposure to rotenone. The results showed that rotenone could significantly inhibit the proliferation rate of PC12 cells and expression of c erbB 2, c myc, p53, and bcl 2 in PC12 cells, NADH could restore the proliferation activity of PC12 cell damaged by rotenone by gene regulation. It is suggested that rotenone could induce PC12 cells apoptosis not only by regulating mitochondria phosphorylation process, but also by down regulating the expression of oncogene proteins (C erbB 2, c myc), anti apoptotic gene protein (bcl 2), p53 tumor suppressor gene protein, and upregulating the expression of the immediate early gene c fos. Regulation of bcl 2, c myc, c erbB 2 and p53 might be involved in the repair of mitochondrial damage of PC12 cells.