Wnt5a在肥胖合并肝细胞癌中表达的初步研究

Preliminary Study on the Wnt5a Expression in Obese Mice with Hepatocellular Carcinoma

目的探讨肥胖合并肝细胞癌中Wnt5a和β-连环蛋白(β-catenin)的表达情况。方法6周龄C57BL/6J小鼠分别给予普通饲料和高脂饲料喂养至14周龄(共8周),肥胖模型造模成功后采用尾静脉注射法将Hepa1-6肝癌细胞株(对照组注射生理盐水)分别接种于体质量正常小鼠和肥胖小鼠,18周龄时处死小鼠,眼眶取血分析相关血清学指标,麻醉下取肝组织后HE染色观察肝脏脂肪变性和肝细胞癌定植情况,免疫组化染色观察Wnt5a和β-catenin的表达情况。结果 18周龄时,高脂饲料喂养的肥胖小鼠肝脏细胞发生脂肪变性;接种肝癌细胞、体质量正常和肥胖小鼠肝组织中均查见肿瘤细胞团,在接种肝癌细胞的肥胖小鼠中可见肝组织灶状坏死。不同处理组小鼠血清总蛋白、天冬氨酸氨基转移酶、谷丙转氨酶、胆固醇和甲胎蛋白差异均有统计学意义(P<0.05)。免疫组化染色结果显示,Wnt5a相对表达量为正常肝组织>肥胖小鼠肝组织>接种肝癌细胞后的体质量正常小鼠肝组织>接种肝癌细胞后的肥胖小鼠肝组织(P<0.05);β-catenin的相对表达量为接种肝癌细胞后的肥胖小鼠肝组织>肥胖小鼠肝组织和接种肝癌细胞后的体质量正常小鼠肝组织>正常肝组织(P<0.05)。结论在肥胖小鼠中Wnt5a的表达下调,β-catenin异常蓄积,可能与肝细胞癌的形成和进展密切相关。

Objective To investigate the Wnt5a expression in obese mice with hepatocellular carcinoma. Methods Two groups of 6-week C57BL/6J mice were fed with chow-diet and high-fat-diet for 8 weeks respectively, to establish obesity model in the latter group. Mice in Hepal-6 group （including normal-body mass mice and obese mice） were injected with Hepal-6 hepatocarcinoma cell lines through caudal vein, while the controls were given NS. Serum and tissue samples were taken at the age of 18 weeks for serological and morphological study. The expression of WntSa and β-catenin in liver were examined by immunohistochemistry. Results At the age of 18-week, ratty degeneration was observed in the livers of obese control mice. Tumor cell masses were found in the livers of both obese and （including normal-body mass mice and obese mice） control mice by inoculation with Hepal-6, while focal necrosis was only observed in the obese＋Hepal-6 group. The levels of serum transaminases, cholesterol and alpha- fetoprotein （AFP） were significantly different between groups （P〈0.05）. The immunohistochemistry showed that the highest expression of Wnt5a was observed in liver tissues of normal control group, followed in sequence by obese control group, normal＋Hepal-6 group, and obese＋Hepal-6 group （P〈0.05）. The expression of β-catenin was just opposite （P〈0.05）. Conclusion The expression of WntSa was decreased, and the β-catenin was abnormal accumulation. It may be closely related to the formation and progression of hepatocellular carcinoma.