线粒体动态学改变在DEHP致大鼠子代神经损伤中的作用

摘要

Objective To investigate the role of mitochondrial dynamic changes in DEHP-induced nerve injury of rat offspring.Methods The pregnant mice were administered with different concentrations of DEHP.Positioning naviga-tion and space exploration experiments was used to detect the neural behavior of 6 months old offspring rats.Enzyme-linked immunosorbent method (PCR)method and immune protein (Western blot)assay was used to detected the mR-NA and protein levels of mitochondrial fusion genes Mfn1 and fission genes Drp1.Results In the offspring rats of DE-HP intrauterine exposure,Latency for seeking submarine platform was significantly prolonged(P < 0.05 ),and the length of the swimming route was increased(P <0.05).The ratio of time/ (length)and total length (length)of the platform is obviously decreased (P <0.05).The mRNA and protein levels of the fusion gene Mfn1 were significantly decreased (P <0.05),while the expression levels of mRNA and protein in the Drp1 were significantly increased (P <0.05).Conclusion Intrauterine exposure to DEHP can induce nerve injury in rats,and the changes of neural behavior may be caused by the imbalance of mitochondrial dynamics.%目的：探讨线粒体动态学改变是否在邻苯二甲酸二乙基己酯（DEHP）损伤子代大鼠神经细胞过程中发挥作用。方法用不同浓度的 DEHP 对妊娠期母鼠进行灌胃，待子鼠出生6周后，利用水迷宫定位航行和空间探索实验检测动物的神经行为学指标，利用酶联免疫吸附法（PCR）法和免疫蛋白（Western blot）法检测子鼠海马细胞线粒体融合基因 Mfn1和分裂基因 Drp1的 mRNA 和蛋白表达的变化。结果DEHP 宫内暴露的子代大鼠寻找平台潜伏期明显延长（P ＜0．05）、游泳路线长度增加（P ＜0．05），平台所在象限游泳的时间／（长度）与总时间（长度）的比明显下降（P ＜0．05），融合基因 Mfn1的 mRNA 和蛋白水平明显下降（P ＜0．05），而分裂基因 Drp1的 mRNA 和蛋白表达水平明显上升。结论宫内暴露 DEHP 可致子代大鼠神经损伤，使神经行为发生改变，而线粒体动态失衡可能是 DEHP改变大鼠神经行为的机制之一。