蛋白激酶C-β/衔接蛋白氧化应激通路介导早产儿氧暴露后体内活性氧簇的产生

摘要

Objective To study the possible mitochondria oxidative stress signal transduction pathway,which probably mediates the production of reactive oxygen species in premature infants exposed to hyperoxia.Methods Hyperoxia group:20 cases of premature infants whose gestational age was below 34 weeks were diagnosed as respiratory failure (treated with exposed to over 400 mL/L oxygen 48-69 h) in Department of Neonatology,the Affiliated Hospital of Luzhou Medical College,from Jul.to Dec.2012.Control group:20 cases of premature infants with the same gestational age were diagnosed as no respiratory failure(exposed to air over 48 h in the same room simultaneously).The expression of protein kinase C-beta (PKC β)/the 66-kDa isoform of the growth factor adaptor Shc (p66Shc)/prolyl isomerase 1 (Pin1)/phosphorylated the 66-kDa isoform of the growth factor adaptor Shc-Ser36 (p66Shc-Ser36) were detected by immunohistochemistry and the production of mitochondrial reactive oxygen was detected by fluorescence microscope in the peripheral blood mononuclear cell of hyperoxia group and control group.Results Compared with the control group,the expressions of PKCβ,p66Shc,Pin1,phosphorylated p66Shc-Ser36 and the production of reactive oxygen in hyperoxia group were significantly increased (t =21.139,5.592,7.476,16.895,10.586,all P ＜ 0.001).There were positive correlations between the production of reactive oxygen and the expressions of PKCβ,p66Shc,Pin1,phosphorylated p66Shc-Ser36 in hyperoxia group(r =0.893,0.795,0.681,0.663,all P ＜ 0.001).Conclusion PKCβ/p66Shc oxidative stress pathway might mediate the production of reactive oxygen species in premature infants exposed to hyperoxia.%目的 研究早产儿氧暴露后体内活性氧簇产生可能的线粒体氧化应激信号传导途径.方法 选择2012年7月至12月胎龄为34周以下在泸州医学院附属医院新生儿科住院诊断为呼吸衰竭需给氧支持治疗的早产儿20例作为高体积分数氧(高氧)组(吸氧体积分数＞400 mL/L,吸氧时间48～69 h),相同时间段置于同一室未用氧的早产儿20例作为对照组,未发生呼吸衰竭,暴露于空气时间＞48 h.用免疫组织化学方法检测高氧组和对照组早产儿外周血单个核细胞内蛋白激酶C-β(PKCβ)、衔接蛋白(p66Shc)、脯氨酰异构酶(Pin1)和胞质磷酸化p66Shc-Ser36蛋白的表达及用荧光显微镜技术检测线粒体活性氧的产生.结果 与对照组相比,高氧组外周血单个核细胞内PKCβ、p66Shc、Pin1和磷酸化p66Shc-Ser36蛋白表达增加及活性氧产生增加,差异均具有统计学意义(t =21.139、5.592、7.476、16.895、10.586,P均＜0.001),且高氧组活性氧的产生与PKCβ、p66Shc、Pinl和磷酸化p66Shc Ser36蛋白表达呈正相关关系(r=0.893、0.795、0.681、0.663,P均＜0.001).结论 PKCβ/p66Shc氧化应激信号通路可能介导早产儿氧暴露后体内活性氧簇的产生.