论文部分内容阅读
背景:促红细胞生成素产生肝细胞受体(erythropoietin-producing hepatocyte receptor,Eph受体)及其ephrin配体极有可能成为疾病治疗的药物靶标。目的:探讨EphA5在先天性甲状腺功能减低大鼠脑中的表达情况及DNA甲基化调控。方法:取交配后的孕C57BL/6大鼠,随机分为甲减组、T4治疗组和对照组。甲减组和T4治疗组从G9开始给予母鼠含0.02%甲巯咪唑的清洁饮用水直至仔鼠全部处死。对照组大鼠一直给予清洁饮用水。T4治疗组从P7开始每日对仔鼠实施腹腔皮下注射T4(0.02μg/g)。结果与结论:在先天性甲状腺功能减低大鼠脑中,EphA5基因和蛋白水平均下调;EphA5基因和蛋白的表达水平在甲减组海马、大脑皮质及小脑中均显著低于对照组(P<0.05),甲减组、治疗组、对照组的EphA5基因和蛋白的表达水平在海马最高、大脑皮质其次、小脑最低,且在甲减组的海马中表达水平下降幅度最大;先天性甲状腺功能减低大鼠海马神经元中,EphA 5启动子CPG岛DNA甲基化水平均显著高于对照组,差异有统计学意义,P<0.05,经相关性分析,发现与EphA5 m RNA表达水平均呈明显负相关(r=-0.937;P<0.05)。提示EphA5信号通道可能参与了先天性甲状腺功能减低大鼠神经元的突触发生障碍;DNA甲基化参与了先天性甲状腺功能减低大鼠海马中EphA5表达的调控,去甲基化治疗可上调先天性甲状腺功能减低大鼠海马神经元中EphA5的表达。
BACKGROUND: Erythropoietin produces an erythropoietin-producing hepatocyte receptor (EphR) and its ephrin ligands are highly likely to be drug targets for disease treatment. Objective: To investigate the expression of EphA5 and the regulation of DNA methylation in congenital hypothyroidism rats. Methods: The pregnant C57BL / 6 rats were randomly divided into hypothyroidism group, T4 treatment group and control group. The hypothyroidism group and the T4 treatment group were given clean drinking water containing 0.02% methimazole from G9 until the rats were sacrificed. Control rats were given clean drinking water. T4 group received intraperitoneal subcutaneous injection of T4 (0.02 μg / g) daily from P7 on a daily basis. RESULTS AND CONCLUSION: EphA5 gene and protein levels were down-regulated in congenital hypothyroidism rats. The expression of EphA5 gene and protein in hippocampus, cerebral cortex and cerebellum of hypothyroidism group was significantly lower than that of control group (P < 0.05). The expression levels of EphA5 gene and protein in the hypothyroidism, treatment and control groups were the highest in the hippocampus, followed by the cerebral cortex, the lowest in the cerebellum, and the highest in the hippocampus in the hypothyroidism group. The congenital hypothyroidism The level of DNA methylation in EphA 5 promoter CPG island was significantly higher in hippocampal neurons of rats than that in control group, the difference was statistically significant (P <0.05). Correlation analysis showed that the expression level of EphA5 mRNA was significantly Negative correlation (r = -0.937; P <0.05). Suggesting that EphA5 signaling pathway may be involved in congenital hypothyroidism in rats neuronal synaptogenesis disorders; DNA methylation involved in congenital hypothyroidism in rats hippocampus EphA5 expression regulation, demethylation therapy may be congenital Expression of EphA5 in Hippocampal Neurons of Hypothyroidism Rats.