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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 expression of Wnt5a and β-catenin in obesity combined with hepatocellular carcinoma. Methods Six-week-old C57BL / 6J mice were fed with normal diet and high-fat diet for 14 weeks (a total of 8 weeks) respectively. Hepa 1-6 hepatocarcinoma cell lines (control group) were injected with tail vein injection Normal saline) were inoculated in normal weight mice and obese mice, respectively, at the age of 18 weeks, mice were sacrificed, orbital blood analysis of serum-related indicators of liver tissue was taken under anesthesia HE staining observed liver steatosis and hepatocellular carcinoma colonization The expression of Wnt5a and β-catenin were observed by immunohistochemistry. Results At 18 weeks of age, fatty degeneration was observed in liver cells of obese mice fed with high-fat diet. Inoculated hepatoma cells, tumor cell mass was observed in liver tissues of both normal and obese mice. In obese mice inoculated with hepatoma cells Visible liver tissue necrosis. The differences of serum total protein, aspartate aminotransferase, alanine aminotransferase, cholesterol and alpha-fetoprotein in different treatment groups were statistically significant (P <0.05). The results of immunohistochemistry showed that the relative expression of Wnt5a in normal liver tissue> liver tissue of obese mice> hepatoma cells inoculated with hepatoma cells> the liver tissue of normal mice> the liver tissue of obese mice after inoculation of hepatoma cells (P <0.05) ; The relative expression amount of β-catenin was liver tissue> normal liver tissue> normal liver tissue (> 0.05) of the liver tissue of the obese mice and the liver tissues of the obese mice after inoculation of the liver cancer cells. Conclusion The down-regulation of Wnt5a and the abnormal accumulation of β-catenin in obese mice may be closely related to the formation and progression of hepatocellular carcinoma.