AIM To study sex disparity in susceptibility to hepatocellular carcinoma(HCC), we created a transgenic mouse model that expressed the full hepatitis B virus(HBV) genome with the W4P mutation.METHODS Transgenic mice we...AIM To study sex disparity in susceptibility to hepatocellular carcinoma(HCC), we created a transgenic mouse model that expressed the full hepatitis B virus(HBV) genome with the W4P mutation.METHODS Transgenic mice were generated by transferring the p HY92-1.1 x-HBV-full genome plasmid(genotype A2) into C57 Bl/6 N mice. We compared serum levels of hepatitis B surface antigen(HBs Ag), interleukin(IL)-6, and the liver enzymes alanine aminotransferase(ALT) and aspartate transaminase(AST), as well as liver histopathological features in male and female transgenic(W4PTG) mice and in nontransgenic littermates of 10 mo of age. RESULTS W4PTG males exhibited more pronounced hepatomegaly, significantly increased granule generation in liver tissue, elevated HBs Ag expression in the liver and serum, and higher serum ALT and IL-6 levels compared to W4PTG females or littermate control groups. CONCLUSION Together, our data indicate that the W4 P mutation in pre S1 may contribute to sex disparity in susceptibility to HCC by causing increased HBV virion replication and enhanced IL-6-mediated inflammation in male individuals. Additionally, our transgenic mouse model that expresses full HBV genome with the W4 P mutation in pre S1 could be effectively used for the studies of the progression of liver diseases, including HCC.展开更多
文摘【目的】研究连翘叶提取物(Forsythia suspensa leaves extract,FSLE)对孕马血清促性腺激素(pregnant mare serum gonadotropin,PMSG)在肝脏中代谢的影响,改善在畜牧生产中因PMSG代谢缓慢而造成的氧化应激。【方法】采用半仿生酶醇法提取连翘叶有效成分,给予昆明雌鼠不同含量的FSLE进行动物体内试验;收集小鼠血清,进行酶联免疫吸附试验,检测各组小鼠血清中PMSG的质量浓度;采集小鼠肝脏组织,检测氧化应激指标谷胱甘肽、超氧化物歧化酶、丙二醛和过氧化氢的水平;采用Western-blot检测小鼠肝脏组织孕烷X受体(pregnane X receptor,PXR)和细胞色素酶P45017A1(cytochrome P45017A1,CYP17A1)蛋白的表达水平。【结果】FSLE可显著降低小鼠血清中PMSG的质量浓度,且可以减缓PMSG代谢引起的氧化应激。Western-blot结果显示:FSLE可显著下调小鼠肝组织中PXR和CYP17A1蛋白的表达。【结论】连翘叶提取物可能是通过下调肝脏中PXR和CYP17A1的表达减缓PMSG代谢引起的氧化应激。
基金Supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute and the Ministry of Health and Welfare,South Korea,No.HI14C0955
文摘AIM To study sex disparity in susceptibility to hepatocellular carcinoma(HCC), we created a transgenic mouse model that expressed the full hepatitis B virus(HBV) genome with the W4P mutation.METHODS Transgenic mice were generated by transferring the p HY92-1.1 x-HBV-full genome plasmid(genotype A2) into C57 Bl/6 N mice. We compared serum levels of hepatitis B surface antigen(HBs Ag), interleukin(IL)-6, and the liver enzymes alanine aminotransferase(ALT) and aspartate transaminase(AST), as well as liver histopathological features in male and female transgenic(W4PTG) mice and in nontransgenic littermates of 10 mo of age. RESULTS W4PTG males exhibited more pronounced hepatomegaly, significantly increased granule generation in liver tissue, elevated HBs Ag expression in the liver and serum, and higher serum ALT and IL-6 levels compared to W4PTG females or littermate control groups. CONCLUSION Together, our data indicate that the W4 P mutation in pre S1 may contribute to sex disparity in susceptibility to HCC by causing increased HBV virion replication and enhanced IL-6-mediated inflammation in male individuals. Additionally, our transgenic mouse model that expresses full HBV genome with the W4 P mutation in pre S1 could be effectively used for the studies of the progression of liver diseases, including HCC.
