葛花解酲方对乙醇性HBV转基因小鼠肝癌癌前病变细胞周期调控因子表达的影响

目的观察葛花解酲方对乙醇性HBV转基因小鼠肝癌癌前病变细胞周期蛋白D1(Cyclin D1)、周期蛋白依赖性激酶4(CDK4)及p27细胞周期调控因子蛋白表达的影响,探讨葛花解酲方阻断肝癌癌前病变的作用机制。方法将24只HBV转基因小鼠适应性饲养1周后,随机分为对照组、模型组、治疗组,每组8只。各组小鼠于22周末进行取材光镜观察肝组织病理学改变并用免疫组织化学法检测Cyclin D1、CDK4及p27KIP1蛋白的表达。结果与模型组比较,给药组肝组织病理形态学得到明显改善;与对照组比较,模型组Cyclin D1和CDK4阳性表达率显著升高(P0.05);与模型组比较,治疗组Cyclin D1和CDK4阳性表达率显著下降(P0.05);与对照组比较,模型组p27KIP1阳性表达率显著降低(P0.05),与模型组比较,治疗组p27KIP1阳性表达率显著升高(P0.05)。结论葛花解酲方可以通过下调癌基因Cyclin D1和CDK4的表达,上调抑癌基因p27KIP1的表达,从而达到保护肝脏损害、逆转肝癌癌前病变的作用。

Effects of Gehua Jiecheng decoction on regulation factors of cell cycle in ethanol-type HBV transgenic mice with hepatocellular carcinoma precan-cerous lesions

Objective To study the effect and mechanism of Gehua Jiecheng decoction (GHJCD),a tra-ditional Chinese herbal medicine compound,on cell cycle regulation factors-Cyclin D1,CDK4 and p27 KIP1 in HBV transgenic mice with hepatocellular carcinoma (HCC)precancerous lesions induced by alcohol.Methods Altogether 24 HBV transgenic mice were randomly divided into normal group,model group and GHJCD group(each n =8).All the mice were sacrificed at the end of the 22 th week,then their livers were dissected.Pathohistological changes of liver were observed by using HE staining,and the expression of CyclinD1,CDK4 and p27 KIP1 protein in hepatic tissue were detected by using immuno-histochemistrical methods.Results Compared with the normal group,the positive expressions of Cy-clinD1 and CDK4 increased and that of p27 KIP1 decreased significantly (P <0.05)in the model group. Compared with the model group,restoration of injured liver tissue was occurred in GHJCD group,and the position expressions of CyclinD1 and CDK4 decreased significantly (P <0.05 )and the expression of p27 KIP1 increased significantly (P <0.05).Conclusion The protective effects of GHJCD on liver injures and HCC precancerous lesions took effects by downregulation of genes of CyclinD1 and CDK4 and upreg-ulation of gene of p27 KIP1 .