原花青素影响Aβ_(25-35)诱导PC12细胞周期变化与细胞凋亡的可能机制

Possible mechanism of proanthocyanidins on abnormal cell cycle and apoptosis of PC12 cells induced by β-amyloid peptide 25-35(Aβ_(25-35))

目的探讨原花青素（Proanthocyanidins，PAC）对β-淀粉样肽（25—35）[β amyloid peptide-（25—35），Aβ25-35]诱导体外血清饥饿培养的PCI2细胞周期异常与凋亡保护作用的可能机制。方法种人培养瓶或板的PC12细胞贴壁后用常用血清饥饿培养使细胞同步于岛期，30mg／L的PAC预处理血清饥饿培养的PC12细胞，加入终浓度为25μmol／L Aβ25-35处理0～20h，通过RT-PCR和Western blot从mRNA及蛋白水平检测细胞周期蛋白依赖性激酶4（Cyclin—dependent kinase-4，CDK4）、磷酸化的视网膜纤维母细胞瘤蛋白（phosphorylated Retinoblastoma protein，pRb）、腺病毒E2启动子结合因子1（Adenovirus E2 factor-1，E2 F1）、B细胞淋巴瘤／白血病关联X蛋白（B-cell lymphoma／leukemia-2 Associated X protein，bax）基因表达的变化。结果与Aβ25—35诱导组比较，CDK4、E2F1、bax mRNA表达和CDK4、pR6、Bax蛋白表达降低。结论PAC可能通过下调CDK4、pRb、E2F1的表达，从而降低bax的活化，对Aβ25-35诱导的PC12细胞周期异常与凋亡起保护作用的。

Objective To study the possible mechanism of proanthocyanidins （PAC） on abnormal cell cycle and apoptosis of serum-deprived PC12 cells induced by t3-amyloid peptide 25-35 （Aβ25-35）. Methods PC12 cells were synchronized by serum deprivation, and then treated with 30 mg/L PAC and 25μmol/L A1325.35 for 0-24 h. Expression of CDK4, pRb, E2F1 and bax mRNA and protein was detected by RT-PCR and Western-blot, respectively. Results Compared with control group, expression of CDK4, E2F1 and bar mRNA, and CDK4, pRb and Mar protein was downregulated in PAC group. Conclusion PAC may diminish the bax activation via downexpression of CDK4, pRb and E2F1, leading to the protection of cell cycle and apoptosis of PCI2 cells against Aβ25-35 induction.