PI3K/Akt通路在中子和γ线致大鼠肠上皮细胞损伤中的变化及IL-11的调控作用  

Changes of PI3K /Akt pathway and regulation 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》2014年第2期196-203,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：目的复制中子和叫线致肠道损伤的体外模型，探讨P13K／Akt通路的变化规律及IL-11对其调控作用，为阐明中子和γ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／mt的rhIL-11，采用Westernblot和图像分析技术检测IEC-6细胞P13K、PDKl、PTEN和Akt表达及活化的变化。结果^y射线照射后6h，IEC-6细胞P13K表达和Akt活化减弱，Akt表达、PDKl及PTEN活化增加；IL-11处理组P13K表达和Akt活化增加，Akt表达、PDKl及PTEN活化减弱。中子照后6h，IEC-6细胞P13K表达减少，24h恢复；照后6-24h，PDKl及trFEN活化增加，Akt活化减弱，程度较γ线更重；IL-11处理组照后6-24h，P13K表达和Akt活化增强，PDKl和ＰＴEN活化减弱，但效果不如在．γ线时显著。结论中子射线对肠上皮细胞P13K／Akt通路活化作用较γ射线更重，且IL-11对抗P13K／Akt通路抑制效果不如γ线时显著。这可能是中子和γ线致伤差异的分子机制，也是中子辐射防护更难的原因。Objective To explore the changes of PI3K/Akt signaling pathway in and protective effect of IL- 11 on neutron and γ-irradiation -induced intestinal epithelial injury, and to provide a molecular base of the neutron and γ - irradiation and explore potential new therapeutics. Methods Intestinal epi- thelium cell line IEC - 6 cells were exposed to 4 Gy neutron or 10 Gy γ- irradiation and treated with 100 ng/ml rhIL- 11 at 12 h prior to or immediately after irradiation. Western Blot and image analysis were used to detect the expressions and activities of PI3K, PDK1, PTEN and Akt. Results At 6 h after -irradiation, the expression of PI3K and activation of Akt in the IEC -6 cells was decreased while the expression of Akt and activities of PDK1 and PTEN were increased. IL - 11 treatment increased the ex- pression of PI3K and activation of Akt, and decreased the expression of Akt and activities of PDK1 and PTEN. The expression of PI3K was decreased at 6 h and recovered at 24 h after 4 Gy neutron irradiation. The activation of PDK1 and PTEN was enhanced, meanwhile the activation of Akt was reduced in 6 - 24 h. Neutron irradiation brought more severe inhibition of PI3 K/Akt than γ- irradiation did. IL - 11 up - regulated the expression of PI3K and activation of Akt, and down - regulated the activation of PDK1 and PTEN in the IEC - 6 cells after neutron irradiation, but it wasn＇ t as effective as in γ- irradiation. Con- clusions Inhibition of PI3K/Akt signaling pathway by neutron irradiation is more severe than that by γ- irradiation, and the protective effect of IL - 11 against PI3 K/Akt signaling pathway activation is less effec- tive than that induced by γ- irradiation. It might be the molecular mechanism of the difference of injury responses induced by neutron and γ - irradiation, tect the body from neutron irradiation. and is also helpful to explain why it is more hard to pro-tect the body from neutron irradiation.

关 键 词：中子 γ射线 肠上皮细胞 大鼠 IL-11 PI3K/AKT 

分 类 号：R818[医药卫生—放射医学]