BDNF对全脑放疗后NFAT3／c4介导的信号通路相关因子作用研究

Effect of brain-derived neurotrophic factor on the NFAT3/c4 signaling pathway after whole brain radiotherapy

目的 观察不同剂量电离辐射对NFAT3/c4信号通路表达的影响以及外源性的BDNF对该通路的改善作用。方法 选用1个月龄SD大鼠分成4个组分别接受单次0、2、10、20 Gy照射,照后3 d进行双侧海马立体定向注射外源性的BDNF。后取脑部海马组织进行蛋白印迹法及PCR技术观察NFAT3/c4相关蛋白表达情况。结果 蛋白印迹法及PCR结果表明电离辐射后NFAT3/c4的表达水平明显下降并呈剂量及时间依赖性。IR＋BDNF组较单纯照射组相比,随着照射剂量增加及时间延长NFAT3/c4和CaN表达水平明显升高。结论 全脑放疗抑制了CaN/NFAT3/c4信号通路,外源性BDNF能促进NFAT依赖的转录,从而改善认知功能的下降。

Objective To explore the effects of various radiation doses on the NFAT3/c4 signaling pathway and the improvement effect of exogenous brain-derived neurotrophic factor （BDNF） on this pathway. Methods Four groups of one-month-old Sprague-Dawley rats received radiation doses of 0, 2, 10, and 20 Gy, respectively, in a single radiation. At three days after radiation, exogenous BDNF was injected stereotaxically into the bilateral hippocampus. Western blotting and RT-PCR were used to assess the levels of NFAT3/c4-related proteins in the hippocampus. Results The results of Western blotting and RT-PCR showed that the level of NFAT3/c4 was reduced in a dose-and time-dependent manner after ionizing radiation. Compared with the radiation alone group, the ionizing radiation plus BDNF group had significantly increased levels of NFAT3/c4 and CaN with increases in radiation dose and time. Conclusions Whole brain radiotherapy inhibits the CaN/NFAT3/c4 signaling pathway. Exogenous BDNF can promote the NFAT-dependent transcription and then improve the cognitive function.