益气活血化瘀法对大鼠肝癌前病变癌基因c-myc、N-ras mRNA表达的影响

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[目的]研究益气活血化瘀法对大鼠肝癌前病变基因c-myc、N-ras mRNA表达水平的影响,从分子生物学水平揭示益气活血化瘀法治疗肝癌前病变的机制及其效果。[方法]将160只Wistar雄性大鼠随机分为4组:正常对照(正常)组、模型组、益气活血化瘀方高剂量(YHHⅠ)组及低剂量(YHHⅡ)组,每组40只。除正常组外,其他组以化学致癌物二乙基亚硝胺(DEN)诱导大鼠建立肝细胞癌(HCC)模型,应用不同剂量益气活血化瘀法中药复方对其诱癌过程实施全程干预。各组在实验的4、8、12、16周时相点取材,利用RT-PCR检测技术与光学显微镜分别对肝细胞增殖相关基因c-myc、N-ras mRNA表达、肝组织病理形态学变化进行动态观察。[结果]在诱癌的不同阶段,YHHⅠ、YHHⅡ组大鼠肝脏病变均明显轻于模型组,且大鼠HCC变进展较模型组明显减缓。与正常组相比,模型组诱癌各期肝组织c-myc、N-ras基因mRNA表达水平明显增高(P<0.05)。诱癌8、12、16周时YHHⅠ、YHHⅡ组c-myc、N-ras基因mRNA表达水平均明显少于模型组(P<0.05);YHHⅠ组与YHHⅡ组比较差异有统计学意义(P<0.05)。[结论]益气活血化瘀法对肝癌前病变癌基因有一定的抑制作用,其机制可能与调控肝细胞增殖基因c-myc、N-ras mRNA表达水平有关 [Objective] To study the effect of Yiqi Huoxue Huayu method on mRNA expression of c-myc and N-ras mRNA in rats with precancerous lesions of liver, and to reveal the mechanism of Yiqi Huoxue Huayu Decoction in treating precancerous lesions of liver cancer from molecular biology level effect. [Methods] 160 Wistar male rats were randomly divided into 4 groups: normal control group, model group, YHH Ⅰ group and low dose YHH Ⅱ group, 40 rats in each group . In addition to the normal group, other groups induced hepatocellular carcinoma (HCC) model by chemical carcinogen diethylnitrosamine (DEN) in rats, and applied different doses of traditional Chinese medicine compound prescription of Qi, Intervention. The groups were taken at 4, 8, 12 and 16 weeks of the experiment. The expression of c-myc and N-ras mRNA and the histopathological changes of liver tissue were detected by RT-PCR and optical microscopy respectively. Dynamic observation. [Result] The liver lesions of rats in YHHⅠ and YHHⅡgroups were obviously lighter than those in model group at different stages of cancer induction, and the progression of HCC in rats was slower than that in model group. Compared with the normal group, the expression of c-myc and N-ras mRNA in the liver tissue of the model group was significantly increased (P <0.05). The mRNA expression levels of c-myc and N-ras in YHHⅠand YHHⅡgroup were significantly less than those in model group at 8th, 12th and 16th week (P <0.05). There was significant difference between YHHⅠgroup and YHHⅡgroup (P < 0.05). [Conclusion] Yiqi Huoxue Huayu method can inhibit the oncogene of precancerous lesions of hepatocellular carcinoma, the mechanism may be related to the regulation of mRNA expressions of c-myc and N-ras in hepatocytes
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