扶正化瘀方抗肝癌前病变的分子机理研究

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目的:研究扶正化瘀方对大鼠肝癌前病变细胞周期调控因子CyclinD1、CDK4蛋白以及癌基因c-myc mRNA表达的影响,从分子水平揭示扶正化瘀方治疗肝癌前病变的机制及其效果。方法:将80只清洁级SD雄性大鼠随机分为空白组、单纯致癌组、扶正化瘀方组、苦参素组,每组20只。除空白组外,其他组以二乙基亚硝胺(DEN)诱导大鼠肝癌前病变模型,应用扶正化瘀方、苦参素对其诱癌过程实施全程干预,共17周。各组大鼠在饲养18周后取材,利用RT-PCR技术与免疫组化对癌基因c-myc mRNA水平、CyclinD1、CDK4蛋白表达及肝组织病理形态学进行观察。结果:扶正化瘀方组、苦参素组大鼠肝脏病变均明显轻于单纯致癌组,与空白组相比,单纯致癌组大鼠肝组织c-myc mRNA水平、CyclinD1、CDK4蛋白表达明显增高(P<0.05)。扶正化瘀方组、苦参素组c-myc mRNA水平、CyclinD1、CDK4蛋白表达均明显少于模型组(P<0.05);扶正化瘀方组与苦参素组比较有统计学意义(P<0.05)。结论:扶正化瘀方对肝癌前病变有一定的抑制作用,其机理可能与调控肝细胞癌基因c-myc mRNA水平以及细胞周期调控因子CyclinD1、CDK4蛋白表达有关。 Objective: To study the effect of Fuzheng Huayu Recipe on the expression of CyclinD1, CDK4 protein and oncogene c-myc mRNA in rat precancerous lesion and to reveal the mechanism and effect of Fuzheng Huayu Recipe in treating precancerous lesion of liver. Methods: Eighty clean SD male rats were randomly divided into blank group, simple carcinogenic group, Fuzhenghuayufang group and oxymatrine group, with 20 rats in each group. Except for the blank group, the other groups were given diethylnitrosamine (DEN) to induce the model of precancerous lesions of liver in rats, and Fuzhenghuayufang and oxymatrine were used to make the whole course of their cancer-inducing process for 17 weeks. The rats in each group were taken for 18 weeks. RT-PCR and immunohistochemistry were used to detect the expression of c-myc mRNA, the expression of CyclinD1 and CDK4 and the histopathology of liver. Results: Compared with the blank group, the liver lesions in the Fuzhenghuayufang group and the matrine group were significantly lighter than those in the blank group. Compared with the blank group, the expression of c-myc mRNA and the expressions of CyclinD1 and CDK4 in the liver of the simple carcinogen group were significantly increased (P <0.05). The levels of c-myc mRNA, CyclinD1, CDK4 in Fuzhenghuayufang and oxymatrine groups were significantly lower than those in model group (P <0.05), while those in Fuzhenghuayufutang and matrine groups were statistically significant (P <0.05). Conclusion: Fuzhenghuayu Recipe can inhibit the precancerous lesions of hepatocellular carcinoma. The mechanism may be related to the regulation of the expression of c-myc mRNA and the expression of CyclinD1 and CDK4.
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