ADLI大鼠肝组织DNA羟甲基化变化及其机制

发布时间：2018-04-19 18:37

本文选题：药物性肝损伤 + 异烟肼　；参考：《山东医药》2017年40期

【摘要】：目的探讨抗结核药物性肝损伤(ADLI)形成过程中DNA羟甲基化变化及其机制。方法选择SD大鼠96只,随机分为异烟肼组、对照组各48只。异烟肼组给予异烟肼55 mg/(kg·d)灌胃,对照组给予等体积蒸馏水灌胃。两组分别于灌胃3、7、10、14、21、28天各随机取8只,麻醉后心脏取血,检测血浆ALT、AST;处死后留取肝组织,HE染色,观察肝组织病理变化;采用RT-PCR法检测肝组织谷胱甘肽S-转移酶P1(GSTP1)基因C、甲基胞嘧啶(5m C)、氧化成羟甲基胞嘧啶(5hm C)含量;采用ELISA法检测肝组织10-11易位蛋白1(TET1)蛋白表达,RT-PCR法检测TET1 mRNA表达。结果随着给药时间延长,异烟肼组肝损伤程度逐渐加重;其GSTP1基因C含量随着肝损伤程度加重呈下降趋势,而5m C含量先上升,至灌胃14天略有回落,随后继续上升;5hm C含量呈现下降趋势,至灌胃21天降至最低,灌胃28天时略有回升;而TET1蛋白水平及其mRNA表达与5hm C含量变化基本一致。结论 DNA羟甲基化可能参与了ADLI的发生。
[Abstract]:Objective to investigate the changes and mechanism of DNA hydroxymethylation during the formation of anti-tuberculosis drug induced liver injury (ADLI). Methods 96 SD rats were randomly divided into isoniazid group (n = 48) and control group (n = 48). Isoniazid group was given isoniazid for 55 mg/(kg d, while the control group was given equal volume distilled water. The rats in the two groups were randomly divided into two groups: 8 rats were randomly selected for 28 days after intragastric perfusion. Blood was taken from the heart after anesthesia and plasma alt AST was detected, and liver tissue was taken for HE staining and pathological changes of liver tissue were observed after death. The content of glutathione S-transferase (GSTP1) gene C, methylcytosine 5 m C ~ (1) was detected by RT-PCR, and the expression of 10 ~ (11) translocation protein (1T _ (T1)) was detected by ELISA method. TET1 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). Results with the prolongation of administration time, the degree of liver injury in isoniazid group was gradually aggravated, the content of GSTP1 gene C in isoniazid group decreased with the severity of liver injury, while the content of 5m C increased first, and decreased slightly at 14 days after administration of isoniazid. The content of 5hm C decreased to the lowest on the 21st day of gastric perfusion, and increased slightly on the 28th day, while the level of TET1 protein and the expression of mRNA were basically consistent with the change of 5hm C content. Conclusion DNA hydroxymethylation may be involved in the pathogenesis of ADLI.
【作者单位】：华北理工大学公共卫生学院;
【分类号】：R575

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