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目的探讨替吉奥对二乙基亚硝胺(Diethylinitrosamine DEN)诱导大鼠原发性肝癌的作用,并探讨其机制。方法采用CCl4增敏、DEN诱导的方法制备大鼠肝癌模型,给药组给予替吉奥灌胃。观察大鼠体重、肝重、肝指数;测定血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)及谷胱甘肽转移酶(r-GT)水平;用苏木素-伊红(HE)染色处理肝脏组织切片,光镜观察病理学改变。免疫组化方法检测PCNA表达。结果模型组有3只动物死亡,替吉奥组动物没有死亡;模型组肝脏湿重及肝脏指数明显大于空白组,替吉奥组明显低于模型组;模型组所有动物均可见肝组织癌变,替吉奥组可见4只动物肝组织癌变,其余8只可见坏死后肝硬化(尚未发生癌变),癌变发生率明显低于模型组;造模动物血清ALT、AST、ALP、γ-GT升高明显,替吉奥明显降低血清ALT、AST、ALP、γ-GT水平。替吉奥组肝硬化及肝癌组织中PCNA蛋白的表达显著低于模型组。结论替吉奥对二乙基亚硝胺诱导的大鼠原发性肝癌有明显的抑制和延缓作用,部分机制可能通过抑制肝癌大鼠肝组织中PCNA蛋白的表达,抑制肝癌细胞过度增殖,从而阻止或延缓大鼠肝癌的发生和发展。
Objective To investigate the effect of tegaserod on rat primary hepatocarcinoma induced by diethylnitrosamine DEN and its mechanism. Methods CCl4-sensitized and DEN-induced rat liver cancer model was established, and the administration group was given gavage. The body weight, liver weight and liver index were observed. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and glutathione transferase r-GT). Liver sections were stained with hematoxylin-eosin (HE) and pathological changes were observed by light microscope. Immunohistochemistry was used to detect PCNA expression. Results In the model group, 3 animals died and the animals in the substitute group did not die. The liver wet weight and liver index in the model group were significantly higher than those in the blank group, Four animals were found to be cancerous in the group of rabbits, and the other eight were found to have cirrhosis after necrosis (no carcinogenesis occurred yet). The incidence of carcinogenesis was significantly lower than that in the model group. The levels of serum ALT, AST, ALP and γ-GT in model animals were increased Obviously, for the Gio significantly lower serum ALT, AST, ALP, γ-GT levels. The expression of PCNA protein in liver cirrhosis and hepatocellular carcinoma was significantly lower than that in model group for the treatment group. Conclusion TIG has obvious inhibitory and delaying effects on diethylnitrosamine-induced primary hepatocellular carcinoma in rats. Some mechanisms may inhibit the proliferation of hepatocarcinoma cells by inhibiting the expression of PCNA protein in liver tissues of rats with hepatocellular carcinoma Prevent or delay the occurrence and development of rat liver cancer.