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BH3-only成员参与辐射诱导的小鼠肝细胞凋亡
陈松,冯旭,邹赢锌,栾洁,张术,周意,储智勇*
0
(海军医学研究所防护医学研究室, 上海 200433)
摘要:
目的 研究细胞凋亡及凋亡相关基因的表达在急性肝脏辐射损伤中的作用。方法 采用BALB/c小鼠以60Co γ射线进行全身照射,建立急性肝脏辐射损伤动物模型,光镜和电镜观察病变48 h。然后采用蛋白质印迹分析法检测肝组织中Caspase 3、Caspase 8、Bcl-2、Bcl-xL、Bax、Bad、PUMA和Slug蛋白表达,并采用原位末端标记法(TUNEL染色)检测细胞凋亡。结果 辐照后4 h出现肝细胞变性和凋亡,辐照后12 h出现细胞坏死,辐照后24~48 h 肝细胞凋亡达到峰值并检测到Caspase 3激活;Bcl-2在辐照后4~24 h上调,于辐照后48 h回落;PUMA在辐照后4~48 h上调;Bcl-xL、Bad在辐照后6~48 h上调;Bax、Slug仅在辐照后12 h上调。结论 辐射诱导的PUMA、Bad表达上调与辐辐照后肝细胞凋亡增加有关。
关键词:    辐射损伤  细胞凋亡  依赖p53上调的凋亡调节子  Bad
DOI:10.3724/SP.J.1008.2014.00837
投稿时间:2013-12-18修订日期:2014-05-25
基金项目:海军医学研究所科研基金(12HY23).
BH3-only members are involved in radiation-induced apoptosis in mouse liver
CHEN Song,FENG Xu,ZOU Ying-xin,LUAN Jie,ZHANG Shu,ZHOU Yi,CHU Zhi-yong*
(Department of Radiological Protection, Naval Medical Research Institute, Shanghai 200433, China)
Abstract:
Objective To study the expression of apoptosis-associated genes and the role of apoptosis in acute radiation-induced liver injury. Methods A mouse radiation model, which was irradiated with 60Co γ ray, was established in this study, and the pathological changes were observed by light and electron microscopy for 48 hours. Western blotting analysis was used to measure the expression of some proteins (Caspase 3,Caspase 8, Bcl-2, Bcl-xL, Bax, Bad, PUMA, Slug) and TUNEL assay was employed to examine cell apoptosis in mouse liver. Results Degeneration and apoptosis were found in the liver at 4 h after irradiation and necrosis occurred at 12 h after irradiation. The peak of apoptosis with activation of Caspase 3 in liver was detected during 24-48 h after irradiation. Bcl-2 protein expression was up-regulated during 4-24 h after irradiation, then was down-regulated at 48 h; PUMA protein was up-regulated during 4-48 h after irradiation; Bcl-xL and Bad protein were up-regulated during 6-48 h after irradiation; and Bax and Slug protein were up-regulated only at 12 h after irradiation. Conclusion Up-regulation of BH3-only members (PUMA and Bad) after irradiation may be associated with the increase of apoptotic cells in the liver.
Key words:  liver  radiation injuries  apoptosis  p53 up-regulated modulator of apoptosis  Bad