ERK通路在中子和γ线致IEC-6细胞损伤中的变化及IL-11的调控作用  

Changes of ERK pathway and regulatory effect of interleukin-11 in intestinal epithelial injury induced by neutron and γ irradiation

作　　者：王瑞娟[1,2] 彭瑞云[2] 高亚兵[2] 常公民[2] 徐新萍[2] 李杨[2] 

机构地区：[1]北京军区总医院附属八一儿童医院,北京100700 [2]军事医学科学院放射与辐射医学研究所,北京100850

出　　处：《中国体视学与图像分析》2013年第4期372-379,共8页Chinese Journal of Stereology and Image Analysis

基　　金：国家自然科学基金资助项目(30700197;81170603)

摘　　要：目的复制中子和γ线致肠道损伤的体外模型，探讨ERK通路的变化规律及IL-11对其调控作用，为阐明中子和1线致伤差异的分子机制并寻找有效的防治措施提供依据。方法采用4Gy中子和10Gy1射线照射IEC-6大鼠肠上皮细胞，并于照射前12h或照射后即刻给予100ng／ml的rhIL-11，采用流式细胞术、Westernblot和图像分析技术，分别检测IEC-6细胞凋亡和坏死率以及Raf-1、MEK1／2、ERK1／2表达及活化的变化。结果中子和叫线均可造成IEC-6细胞损伤，且前者损伤更重；应用IL-11后，二组凋亡率和坏死率均出现下降。1射线照射后6～24h，IEC．6细胞Raf-1表达和活化及MEK1／2活化升高，ERK1／2活化减弱，IL-11处理组于照射后5～15min可增加Raf-1和MEK1／2活性，照射后6h抑制ERK1／2活化。中子照后6～24h，Raf-1表达和活化及MEK1／2活化无明显变化，ERK1／2表达和活化升高，与照射组比较，IL-11处理后6h，Raf-1表达变化不明显，照射后6～24h，MEK1／2活化升高，IL-11在照射后6h抑制ERKl／2活化，照后24h增加ERK1／2表达及活化。结论中子照射造成IEC-6细胞ERK1／2活化，而γ射线照射则表现为抑制作用；IL-11通过调控ERK通路对二者造成的肠损伤具有防护作用。Objective To explore the changes of ERK signaling pathway and protective effect of IL-11 on intestinal epithelial injury induced by neutron and y irradiation, and to provide a molecular basis for dif- ferent effects of neutron and y irradiation and development of new potential therapeutics. Methods Intestinal epithelium cell line No. 6 （IEC-6） cells were exposed to 4 Gyneutron or 10 Gy y irradiation and treated with 100 ng/ml rhIL-11 12 h prior to or immediately after irradiation. Flow cytometry, western blot and image analysis were used to detect the cell death and expression and activity of Raf-1, MEK1/2 and ERK1/2. Results Both neutron and ＂,/ irradiation, especially neutron irradiation, could damage IEC-6 cells. After IL-11 treatment the rate of apoptosis and activity of Raf-1 and MEK1/2 activity were and necrosis of IEC-6 cells was reduced. The expression increased, however, ERK1/2 activity decreased at 6- 24 h after γ irradiation. In the IL-11-treated group, the activities of Raf-1 and MEK1/2 were increased at 5 - 15 min after irradiation, and ERK1/2 activity inhibited at 6 h after irradiation. The expression and ac- tivity of Raf-1 and MEK1/2 showed no significant changes at 6 -24 h after neutron irradiation, while the expression and activity of ERK1/2 increased. Compared with the irradiation group, the Raf-1 expression was not significantly changed at 6 h after IL-11 treatment,and MEK1/2 activity was increased at 6 -24 h after IL-11 treatment. IL-11 treatment inhibited the ERK1/2 activity at 6 h after irradiation, and in- creased the ERK1/2 expression and activity at 6 - 24 h after irradiation. Conclusions ERK1/2 in IEC-6 cells is continuously activated by neutron irradiation,while inhibited by y irradiation. IL-11 may confer protective effects to the IEC-6 cells from neutron and y radiation injury via ERK pathway

关 键 词：中子γ射线 IEC-6细胞 IL 11 ERK 

分 类 号：R363[医药卫生—病理学]