CAJ | 학술논문

目的：探讨PRX2和AKR1B10在二阶段化学诱发小鼠肝癌形成过程中的表达及意义。方法90只C57BL/6J雄性小鼠随机分为实验组（60只）和正常对照组（30只），用DEN/CCl4/乙醇诱发小鼠肝癌。于第4周、第8周、第12周、第16周和第20周5个时点处死小鼠，观察其肝脏病理组织的改变，应用实时荧光定量PCR法、免疫组化SP法分别检测小鼠肝组织PRX2 mRNA和AKR1B10 mRNA及蛋白质的表达水平。结果①实验诱发小鼠肝癌过程中的第4周见肝细胞肿胀，炎细胞浸润，肝脏呈炎症病变；第8周见肝组织炎症病变加重，出现纤维组织增生及肝细胞再生；第12周见肝组织呈不典型增生；第16周有典型假小叶形成；第20周可见典型的小鼠肝癌病理改变。②化学诱癌的第4周至第20周实验组小鼠肝组织PRX2 mRNA和AKR1B10 mRNA和蛋白质的表达均高于正常对照组（P<0.05），且两者的表达水平随着时间的延长，均呈逐步升高的趋势；至第20周肝癌形成时，实验组两者的表达均显著高于癌前各时间点（P<0.05）。③在二阶段化学诱发小鼠肝癌形成过程中，PRX2 mRNA和AKR1B10 mRNA的表达水平呈正相关（r=0.674，P=0.05）。结论在二阶段化学诱发小鼠肝癌形成过程中PRX2和AKR1B10的高表达是化学诱发小鼠肝癌形成的早期事件，PRX2和AKR1B10可能在化学诱发小鼠肝癌的发生、发展和促进过程中起重要作用。
목적：탐토PRX2화AKR1B10재이계단화학유발소서간암형성과정중적표체급의의。방법90지C57BL/6J웅성소서수궤분위실험조（60지）화정상대조조（30지），용DEN/CCl4/을순유발소서간암。우제4주、제8주、제12주、제16주화제20주5개시점처사소서，관찰기간장병리조직적개변，응용실시형광정량PCR법、면역조화SP법분별검측소서간조직PRX2 mRNA화AKR1B10 mRNA급단백질적표체수평。결과①실험유발소서간암과정중적제4주견간세포종창，염세포침윤，간장정염증병변；제8주견간조직염증병변가중，출현섬유조직증생급간세포재생；제12주견간조직정불전형증생；제16주유전형가소협형성；제20주가견전형적소서간암병리개변。②화학유암적제4주지제20주실험조소서간조직PRX2 mRNA화AKR1B10 mRNA화단백질적표체균고우정상대조조（P<0.05），차량자적표체수평수착시간적연장，균정축보승고적추세；지제20주간암형성시，실험조량자적표체균현저고우암전각시간점（P<0.05）。③재이계단화학유발소서간암형성과정중，PRX2 mRNA화AKR1B10 mRNA적표체수평정정상관（r=0.674，P=0.05）。결론재이계단화학유발소서간암형성과정중PRX2화AKR1B10적고표체시화학유발소서간암형성적조기사건，PRX2화AKR1B10가능재화학유발소서간암적발생、발전화촉진과정중기중요작용。
Objective To explore the expression and significance of PRX2 and AKR1B10 during chemically induced hepatocar-cinogenesis in mice. Methods Primary hepatocellular carcinoma(HCC)was induced in 60 C57BL/6J mice by exposing them to a combination of diethylnitrosamines(DEN),carbon tetrachloride(CCl4)and ethanol. Another group of 30 mice received no drugs and served as a negative control.Mice were killed on weeks 4,8,12,16 and 20 and tissue samples were harvested for staining with hematoxylin and eosin.Samples were also analyzed by QPT-PCR and immunohistochemistry to detect changes in PRX2 and AKR1B10 mRNA and protein. Results In mice with chemically induced HCC,toxic hepatitis and acute hepatocellular necrosis were observed by week 4.By week 8,hepatocellular necrosis had gotten worse and liver fibrosis was detectable.Atypical hyperplasia was observable by week 12,pseudolobule by week 16 and hepatocellular carcinoma by week 20.Expression of PRX2 and AKR1B10 was significantly higher in the HCC animals than in control animals from week 4 to 20(P<0.05),and levels continued to increase with time.Levels were significantly higher in the HCC animals by week 20 than before chemical induction of HCC(P<0.05).Expres-sion of PRX2 mRNA positively correlated with that of AKR1B10 mRNA (r=0.674,P=0.05). Conclusion Overexpression of PRX2 and AKR1B10 may be early events during chemically induced hepatocarcinogenesis in mice and may promote hepatocarcinogenesis.