首页> 中文期刊>中华放射肿瘤学杂志 >978-1对小鼠放射性脑损伤的作用及分子机制

978-1对小鼠放射性脑损伤的作用及分子机制

摘要

Objective To evaluate the traditional Chinese medicine destagnation and renal invigoration (987-1) in the prevention and treatment of impaired ability of learning and memory in radiation injury as studied by subependymal cells (SEC) and correlative gene expression.  Methods Mice were randomly assigned into three groups: radiation plus 978-1, radiation alone and control. Step down method was used to measure the average error number, incubation period of mice after irradiation. The number of SEC, apoptotic index and expression of p53, C-jun and C-fos of mice after radiation with and without 978-1 were counted.  Results Twenty-four hours after anaesthesia and irradiation, the survival rate of mice were 64.7% for radiation plus 978-1, 47.6% for radiation alone and 85.3% for control, respectively. From week 12 after irradiation, the difference in body weight between mice with or without 978-1 increased gradually. From week 48 after radiation, the body weight of mice with and without 978-1 were 46.7%±4.6% and 39.0%±2.4% (P=0.03). After radiation, the SEC cellularity of mice with 978-1 become more than that of mice without 978-1. Six hours after irradiation, the apoptotic index of SEC in mice with and without 978-1 were 3.4% and 8.1%, respectively (P=0.00), and the apoptotic index in both groups peaked in hour 24 (17.1% vs 37.1%, P=0.00). The C-fos expression of SEC of mice with and without 978-1 were 12.6% and 30.5% (P=0.00), both peaked in hour 2 after irradiation. The C-jun expression of SEC of the mice with and without 978-1 were 16.8% and 46.5%, respectively (P= 0.00), both peaked in hour 6 after irradiation. The p53 expression of SEC in mice with and without 978-1 were 28.7% and 66.6%, respectively (P= 0.00), both peaked in hour 24 after irradiation.  Conclusions  Traditional Chinese medicine of destagnation and renal invigoration (978-1) is useful to prevent or treat the damage of learning and memory ability caused by irradiation in mice. It is able to prevent or treat radiation-induced SEC damage by down-regulation of p53 and C-jun expression and inhibition of apoptosis.%目的 研究活血化淤配伍补肾中药978-1对放射性脑损伤的作用及其分子机制。方法  以20?Gy的电子线(10?MeV)照射小鼠全脑建立动物模型;随机分为中药+照射组、单纯照射组、对照组;采用跳台法测定小鼠平均错误数、第1次受电击的潜伏期;制作鼠脑病理切片,采用HE染色和免疫组织化学染色研究鼠大脑室管膜下区细胞(SEC)数、细胞凋亡指数和p53、C-jun、C-fos基因表达率。结果 ①小鼠麻醉、受照射后均在24?h内苏醒,中药+照射组、单纯照射组、对照组生存率分别为64.7%、47.6%、85.3%(χ2=2.6,P=0.09); ②12周之后中药+照射组、单纯照射组体重之间的差异逐渐增大,48周时中药+照射组体重明显高于单纯照射组(F=7.3,P=0.03);③照射后不同时间中药+照射组昆明鼠的SEC数均高于单纯照射组;④中药+照射组、单纯照射组照射后6?h昆明鼠大脑SEC凋亡率分别为3.4%和8.1%(F=20.6,P=0.00),24?h达到高峰,分别为17.1%和37.0%(F=62.6,P=0.00);⑤照射后2?h C-fos表达率达到高峰,中药+照射组低于单纯照射组,分别为12.6%和30.5%(F=52.5,P=0.00);⑥照射后6?h C-jun表达率达到高峰,中药+照射组低于单纯照射组,分别为16.8%和46.5%(F=166.7,P=0.00);⑦照射后24?h p53表达率达到高峰,中药+照射组也低于单纯照射组分别为28.7%和66.6%(F=100.6,P=0.00)。结论 ①活血化淤配伍补肾中药978-1具有防治学习记忆力放射性损伤的作用。②活血化淤配伍补肾中药能防治SEC放射性损伤,其作用机制与下调p53、C-jun基因表达进而抑制细胞凋亡有关。

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