miRNA-122在异烟肼肝损伤大鼠中的调控机制

发布时间：2018-10-24 16:10

【摘要】：目的:探讨miRNA-122在异烟肼致大鼠肝损伤中的调控机制。方法:采用异烟肼55 mg·kg-1·d-1连续灌胃3,7,10,14,21,28 d建立肝损伤大鼠模型,对照组给予等容积纯化水灌胃。全自动生化分析仪检测血清丙氨酸氨基转移酶(ALT)、门冬氨酸转移酶(AST)活性;比色法检测肝组织中MDA含量和SOD酶活力,实时荧光定量PCR(RT-PCR)方法检测肝组织中miRNA-122、pri-miRNA-122、HNF4α、C/EBPα、Cycling G1、CAT-1表达水平;酶联免疫吸附法(ELISA)检测Cycling G1、CAT-1蛋白表达水平。结果:与对照组比较,肝组织病理变化在7 d表现为肝损伤;血浆ALT、AST的水平呈升高趋势(均P0.01),且均在10 d发生明显上升(P0.05);各用药组肝组织MDA含量逐渐升高,SOD活力却逐渐下降,miRNA-122表达水平整体呈下降趋势(P0.01),其上游pri-miRNA-122及转录因子HNF4α、C/EBPαmRNA表达水平整体呈下降趋势(均P0.01),其下游靶基因CyclingG1、CAT-1的mRNA及蛋白表达水平均呈上升趋势(均P0.01)。结论:转录因子HNF-4α、C/EBPα调控miRNA-122低表达,miRNA-122低表达进一步调控其下游靶基因Cycling G1、CAT-1参与异烟肼致肝损伤的过程。
[Abstract]:Objective: to investigate the regulatory mechanism of miRNA-122 in rat liver injury induced by isoniazid. Methods: isoniazid 55 mg kg-1 d-1 was used to establish the rat model of liver injury for 28 days. The control group was treated with purified water in the same volume. The activity of serum alanine aminotransferase (ALT),) aspartate transferase (AST) was detected by automatic biochemical analyzer, the content of MDA and the activity of SOD in liver tissue were detected by colorimetry, and the expression levels of miRNA-122,pri-miRNA-122,HNF4 伪, C/EBP 伪, Cycling G1 CAT-1 in liver tissue were detected by real-time quantitative PCR (RT-PCR) method. The expression of Cycling G 1 and CAT 1 protein was detected by enzyme linked immunosorbent assay (ELISA). Results: compared with the control group, the pathological changes of liver tissue showed liver injury at 7 days. The level of plasma ALT,AST increased (P0.01), and increased significantly on the 10th day (P0.05), the content of MDA in liver tissue increased gradually, the activity of SOD decreased gradually, the expression of miRNA-122 decreased gradually (P0.01), and the upstream pri-miRNA-122 and transcription factors in all groups were decreased (P0.01). The expression of HNF4 伪 and C/EBP 伪 mRNA decreased (all P0.01), and the mRNA and protein expression of CyclingG1,CAT-1 in the downstream gene showed an upward trend (P0.01). Conclusion: the transcription factors HNF-4 伪 and C/EBP 伪 regulate the low expression of miRNA-122, and the low expression of miRNA-122 further regulates the downstream target gene Cycling G1, CAT-1, which is involved in the process of isoniazid induced liver injury.
【作者单位】：华北理工大学公共卫生学院河北省煤矿卫生与安全重点实验室;
【基金】：唐山市重点实验室资助项目(编号:08150201A-1-8)
【分类号】：R965

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