目的 观察大鼠诱发肝癌过程中Sonic Hedgehog(Shh)信号通路相关基因的表达变化,探讨其在肝癌发生发展过程中的作用.方法 雄性Wistar大鼠48只,随机分成4组,利用二乙基亚硝胺(DEN)制备诱发性大鼠肝癌模型,应用原位核酸杂交技术检测Shh、Ptc、Gli1 mRNA在对照组、模型组(6w)、模型组(14w)、模型组(22w)大鼠肝脏癌变过程中的表达变化.结果 在模型组(6w)大鼠肝脏的肝小叶周边可见嗜酸性、气球样变性等肝细胞损伤的表现,模型组(14w)大鼠肝脏中可见肝假小叶和非典型增生结节,模型组(22w)大鼠肝脏中可见到高分化的肝细胞癌结节.Shh、Ptc、Gli1 mRNA阳性表达细胞主要分布在大鼠肝脏中的肝细胞损伤区、增生结节、癌结节、小叶间胆管上皮和癌旁组织中,Shh、Ptc、Gli1 mRNA在模型组的大鼠肝组织中表达的平均光密度值均高于对照组.结论 Shh信号通路在诱癌过程中异常激活,可能促进肝损伤后的正常修复、异常增殖及肝细胞癌变过程.%Objective To study the expression of genes related to Sonic Hedgehog(Shh) of rat liver cancer model, and to approach their function and significance in the process of liver cancer development. Methods 48 male Wistar rats were divided into 4 groups at random, and the DEN-induced hepatocarcinogenesis model was established. Based on this model, the expressions of Shh, Ptc, Gli1 mRNA were detected with in situ hybridization in the rat liver of the control and model groups (6w, 14w and 22w). Results In the model group (6w), hepatocellular injury including eosinophilic, balloon-like degeneration was observed in the outer edge of hepatic lobules. In the model group (14w) , liver pseudolobules and atypical hy-perplastic nodules were observed. And cancerous nodes of well-differentiated hepatocellular carcinoma were found in the model group (22w). The positive expression cells of Shh, Ptc, Gli1 mRNA were mainly distributed around the zone of liver damage, atypical hyperplastic nodules, cancer nodules, the epithelial of interlobular bile duct and peritumoral tissue. The average optical density of Shh, Ptc, Gli1 mRNA expressions in the model groups was higher than in the contral groups respectively. Conclusion The Shh signal pathway is abnormally activated, which may promote the repair processes after liver damage, the abnormal proliferation, and the hepatocyte canceration.
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