【摘要】：目的:探討miRNA-122在異煙肼致大鼠肝損傷中的調(diào)控機(jī)制。方法:采用異煙肼55 mg·kg-1·d-1連續(xù)灌胃3,7,10,14,21,28 d建立肝損傷大鼠模型,對照組給予等容積純化水灌胃。全自動生化分析儀檢測血清丙氨酸氨基轉(zhuǎn)移酶(ALT)、門冬氨酸轉(zhuǎn)移酶(AST)活性;比色法檢測肝組織中MDA含量和SOD酶活力,實時熒光定量PCR(RT-PCR)方法檢測肝組織中miRNA-122、pri-miRNA-122、HNF4α、C/EBPα、Cycling G1、CAT-1表達(dá)水平;酶聯(lián)免疫吸附法(ELISA)檢測Cycling G1、CAT-1蛋白表達(dá)水平。結(jié)果:與對照組比較,肝組織病理變化在7 d表現(xiàn)為肝損傷;血漿ALT、AST的水平呈升高趨勢(均P0.01),且均在10 d發(fā)生明顯上升(P0.05);各用藥組肝組織MDA含量逐漸升高,SOD活力卻逐漸下降,miRNA-122表達(dá)水平整體呈下降趨勢(P0.01),其上游pri-miRNA-122及轉(zhuǎn)錄因子HNF4α、C/EBPαmRNA表達(dá)水平整體呈下降趨勢(均P0.01),其下游靶基因CyclingG1、CAT-1的mRNA及蛋白表達(dá)水平均呈上升趨勢(均P0.01)。結(jié)論:轉(zhuǎn)錄因子HNF-4α、C/EBPα調(diào)控miRNA-122低表達(dá),miRNA-122低表達(dá)進(jìn)一步調(diào)控其下游靶基因Cycling G1、CAT-1參與異煙肼致肝損傷的過程。
[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 偽, C/EBP 偽, 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 偽 and C/EBP 偽 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 偽 and C/EBP 偽 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.
【作者單位】： 華北理工大學(xué)公共衛(wèi)生學(xué)院河北省煤礦衛(wèi)生與安全重點實驗室;
【基金】：唐山市重點實驗室資助項目(編號:08150201A-1-8)
【分類號】：R965

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