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肝癌相关基因CYP2E1在急性肝损伤的乙肝病毒转基因小鼠中的表达

Liver cancer-related gene CYP2E1 expression in HBV transgenic mice with acute liver injury.

作者信息

Zhang Chun, Wei Qin, Jiang Tao, Shou Xi, Li Zhi-Qiang, Wen Hao

机构信息

Xinjiang Key Laboratory for Medical Animal Model Research, First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushan Road, Urumqi, Xinjiang, 830054, China.

出版信息

Tumour Biol. 2014 Apr;35(4):3671-7. doi: 10.1007/s13277-013-1486-4. Epub 2013 Dec 8.

Abstract

The objective of this research was to study the CYP2E1 gene expression in carbon tetrachloride (CCl4)-induced acute liver injury in hepatitis B virus (HBV) transgenic mice. Twenty-four HBV(-) and 24 HBV(+) transgenic mice aged 8 to 10 weeks were selected for the present study. Intraperitoneal injection of 1.0 μL/g of CCl4 (1:4 dissolved in olive oil) to mice was performed to induce acute liver injury model. Eight normal clean-grade C57BL/6 mice were taken as the control group. The control group received saline intraperitoneally. The mice in each group were killed 3, 6, 12, 24, 48, and 72 h after injection. The liver tissue samples of mice were collected. The liver histological changes at different time points in each group were observed under light microscope. The quantitative PCR methods were utilized to measure the relative mRNA levels of CYP2E1 gene in liver tissues. Immunohistochemistry and Western blot techniques were used to observe tissue expression levels of CYP2E1 in each group. Compared with that of the control group, mRNA and protein expression levels of CYP2E1 significantly increased both in the HBV(-) group and in the HBV(+) group after the CCl4 induced the acute liver injury, and it reached the peak at 72h after the CCl4 injection. Compared with the HBV(-) group, the mice in the HBV(+) group had severe liver damage and significantly increased CYP2E1 gene and protein expression levels. In the CCl4-induced acute liver injury of HBV transgenic mice, the CYP2E1 gene expression significantly increased. The results provided evidence for the HBV-induced liver damage and liver cancer pathogenesis.

摘要

本研究的目的是探讨细胞色素P450 2E1(CYP2E1)基因在四氯化碳(CCl4)诱导的乙型肝炎病毒(HBV)转基因小鼠急性肝损伤中的表达情况。本研究选取了24只8至10周龄的HBV(-)转基因小鼠和24只HBV(+)转基因小鼠。通过腹腔注射1.0 μL/g的CCl4(1:4溶于橄榄油)诱导小鼠急性肝损伤模型。选取8只正常清洁级C57BL/6小鼠作为对照组,对照组小鼠腹腔注射生理盐水。每组小鼠在注射后3、6、12、24、48和72小时处死。收集小鼠肝脏组织样本。在光学显微镜下观察每组不同时间点的肝脏组织学变化。采用定量PCR方法检测肝脏组织中CYP2E1基因的相对mRNA水平。利用免疫组织化学和蛋白质印迹技术观察每组中CYP2E1的组织表达水平。与对照组相比,CCl4诱导急性肝损伤后,HBV(-)组和HBV(+)组中CYP2E1的mRNA和蛋白表达水平均显著升高,并在CCl4注射后72小时达到峰值。与HBV(-)组相比,HBV(+)组小鼠肝损伤更严重,CYP2E1基因和蛋白表达水平显著升高。在CCl4诱导的HBV转基因小鼠急性肝损伤中,CYP2E1基因表达显著增加。该结果为HBV诱导的肝损伤和肝癌发病机制提供了证据。

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