目的 探讨维药异常黑胆质成熟剂在异常黑胆质型肝癌病证大鼠模型中的抗肝癌作用.方法 90只清洁级雄性Wistar大鼠按随机数字表法分成正常组、对照肝癌组、异黑肝癌组和成熟剂高、中、低剂量组6组,每组各15只.正常组正常饲养,对照肝癌组正常饲养21 d后给予二乙基亚硝胺(DEN)20周诱导肝癌.异黑肝癌组和成熟剂高、中、低剂量组大鼠通过干寒属性饲料、干寒气候环境、足底电刺激,夹尾以及强迫游泳等多因素复合作用21d建立异常黑胆质证载体动物模型,再加用DEN20周诱导建立异常黑胆质型肝癌病证模型;DEN诱导的同时,成熟剂高、中、低剂量组用异常黑胆质成熟剂按高、中、低(6.0、3.0、1.5 g/kg)剂量进行干预.提取肝组织中mRNA,利用基因芯片技术筛选出的大鼠肝脏差异表达的Id4和p21候选基因并用RT-qPCR法验证.结果 与正常组比较,对照肝癌组肝组织Id4基因表达下调(P＜ 0.01);与对照肝癌组比较,异黑肝癌组肝组织Id4基因表达下调(P＜ 0.01);与异黑肝癌组相比,成熟剂高、中、低剂量肝组织Id4基因表达均上调,其中成熟剂高、中剂量组升高显著(P＜0.01).与正常组相比,对照肝癌组肝组织p21基因表达上调(P＜0.01);与对照肝癌组比较,异黑肝癌组肝组织p21基因表达上调(P＜0.05);与异黑肝癌组相比,成熟剂高、中、低剂量肝组织p21基因表达均下调,其中成熟剂中、低剂量组下降明显(P＜0.01).结论 异常黑胆质成熟剂可影响异常黑胆质型肝癌病证模型大鼠肝脏Id4和p21基因的mRNA表达水平.%Objective To investigate the anticancer role of Uyghur medicine Abnormal Savda Munziq (ASM) in abnormal savda hepatocellular carcinoma rat models.Methods 90 male Wistar rats were divided into 6 groups,including normal group,control hepatic carcinoma group,abnormal savda hepatocellular carcinoma group and ASM high,middle and low dosage group by random number table,with 15 cases in each group.The normal group rats were placed in normative feeding environment.After 21 days of feeding in laboratory environment,the control hepatic carcinoma group rats were induced by diethylnitrosamine (DEN) 20 weeks to establish the liver cancer rat model.The rats in the abnormal savda hepatocellular carcinoma group,ASM high,middle and low dosage group were established abnormal black bile models,through dry cold property feed,dry cold climate environment,plantar electrical stimulation,tail and forced swimming,etc;after 21 days they were induced by DEN for 20 weeks to establish the abnormal savda hepatocellular carcinoma models.At the same time,the rats in the ASM high,middle and low dosage group were intervened by 6.0,3.0,1.5 g/kg of ASM.The mRNA was extracted from liver tissue and Id4,p21 gene were verified by RT-qPCR after screened by gene chip technology.Results The Id4 gene expression in liver tissue was down-regulated in control hepatic carcinoma group,compared with the normal control group (P ＜ 0.01).The Id4 gene expression in liver tissue was down-regulated in abnormal savda syndromeliver cancer group,compared with the control hepatic carcinoma group (P ＜ 0.01).Compared with the abnormal savda hepatocellular carcinoma group,the expression of Id4 gene in liver tissue was up-regulated all in ASM high,middle and low dosage group,the high and middle dosage groups were obviously up-regulated (P ＜ 0.01).Compared with the normal group,the liver tissue p21 gene expression was up-regulated in control hepatic carcinoma group (P ＜ 0.01).The p21 gene expression in liver tissue wasup-regulated in abnormal savda syndromeliver cancer group,compared with the control hepatic carcinoma group (P ＜ 0.05).Compared with the abnormal savda hepatocellular carcinoma group,the expressions of p21 gene were down-regulated all in ASM high,middle and low dosage group,the middle and low dosages group were dramatic decline (P ＜ 0.01).Conclusion The ASM could have an impact on mRNA expressions of Id4 and p21 gene in abnormal savda hepatocellular carcinoma rat models.
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