葛花解酲方对乙醇性HBV转基因小鼠肝癌前病变GST-Pi和PCNA表达及Wnt/β-catenin信号通路的影响  

Effects of Gehua Jiecheng decoction on expression of GST-Pi and PCNA and Wnt/β-catenin signaling pathway in precancerous lesions of ethanol-induced HBV transgenic mice

作　　者：吴文宇 杨柱 龙奉玺 罗莉 魏显鳗 税会利 唐东昕 WU Wen-Yu;YANG Zhu;LONG Feng-Xi;LUO Li;WEI Xian-Man;SHUI Hui-Li;TANG Dong-Xin(Department of Oncology,First Affiliated Hospital of Chinese University of Traditional Chinese Medicine,Guiyang 550001,China)

机构地区：[1]贵州中医药大学第一附属医院肿瘤科,贵阳550001 [2]贵州中医药大学,贵阳550025 [3]贵航贵阳医院肿瘤科,贵阳550009

出　　处：《中国免疫学杂志》2020年第1期36-41,共6页Chinese Journal of Immunology

基　　金：国家自然科学基金项目(81160417)

摘　　要：目的:探讨葛花解酲方对乙醇性乙型肝炎病毒(HBV)转基因小鼠肝癌前病变谷胱甘肽-S转移酶(GST-Pi)和增殖细胞核抗原(PCNA)表达及Wnt/β-连环蛋白(β-catenin)信号通路的影响。方法:将100只HBV转基因小鼠根据随机数字法分为对照组、模型组、葛花解酲方组和葛花解酲方+氧化锂(LiCl)组,每组25只。红星二锅头灌胃建立肝癌癌前病变小鼠模型,葛花解酲方水煎剂(40 g/kg)灌胃干预肝癌癌前病变,Wnt/β-catenin激动剂LiCl[1 mEq/(kg·d)]灌胃干预Wnt/β-catenin信号通路,共20周。伊红-苏木素(HE)染色观察肝脏病理学变化,免疫组化染色测定肝脏GST-Pi和PCNA表达,Western blot测定肝脏组织中Wnt-1、β-catenin蛋白水平。结果:与对照组比较,模型组小鼠肝脏重量、肝脏指数、GST-Pi IDO、PCNA IDO、Wnt-1和β-catenin蛋白升高(P<0.05);与模型组比较,葛花解酲方组小鼠肝脏重量、肝脏指数、GST-Pi IDO、PCNA IDO、Wnt-1和β-catenin蛋白降低(P<0.05);与葛花解酲方组比较,葛花解酲方+LiCl组小鼠肝脏重量、肝脏指数、GST-Pi IDO、PCNA IDO、Wnt-1和β-catenin蛋白升高(P<0.05)。HE染色:对照组小鼠肝脏结构和形态正常;模型组小鼠肝细胞变质和结节性增生明显,可见典型的假小叶,炎症细胞浸润明显,胆管上皮增生并具有异型性;葛花解酲方组小鼠肝细胞变质、结节性增生、炎症细胞浸润、胆管上皮增生及异型性较轻;葛花解酲方+LiCl组小鼠肝细胞变质、结节性增生、炎症细胞浸润、胆管上皮增生及异型性介于模型组和葛花解酲方组之间。结论:葛花解酲方可能通过抑制Wnt/β-catenin信号通路降低肝组织GST-Pi和PCNA表达逆转乙醇性HBV转基因小鼠肝癌前病变的发生。Objective:To investigate the effects of Gehua Jiecheng decoction on expression of glutathione-S transferase(GST-Pi)and proliferating cell nuclear antigen(PCNA)and Wnt/β-catenin signaling pathway in hepatocellular carcinoma precancerous lesions of ethanol-type hepatitis B virus(HBV)transgenic mice.Methods:100 HBV transgenic mice were divided into control group,model group,Gehua Jiecheng group and Gehua Jiecheng+lithium oxide(LiCl)group accorded to random number method,with 25 rats in each group.Red star Erguotou was intragastric administration to establish the mouse model of hepatocellular carcinoma precancerous lesions.Gehua Jiecheng decoction(40 g/kg)was intragastric administration to intervene hepatocellular carcinoma precancerous lesions.Wnt/β-catenin agonist LiCl[1 mEq/(kg·d)]was intragastrically administered to intervene the Wnt/β-catenin signaling pathway,for 20 weeks.Hematoxylin-Eosin(HE)staining was used to observe liver pathological changes.Immunohistochemical staining was used to measure the expression of GST-Pi and PCNA in liver.The levels of Wnt-1 andβ-catenin in liver tissues were determined by Western blot.Results:Compared with the control group,the liver weight,liver index,GST-Pi IDO,PCNA IDO,the protein levels of Wnt-1 andβ-catenin in the model group were increased(P<0.05).Compared with the model group,the liver weight,liver index,GST-Pi IDO,PCNA IDO,the protein levels of Wnt-1 andβ-catenin were decreased in the Gehua Jiecheng group(P<0.05).Compared with Gehua Jiecheng group,the liver weight,liver index,GST-Pi IDO,PCNA IDO,the protein levels of Wnt-1 andβ-catenin were increased in Gehua Jiecheng+LiCl group(P<0.05).HE staining:in the control group,the liver structure and morphology of mice were normal;in the model group,the hepatic cell metamorphism and nodular hyperplasia were obvious,the typical pseudolobules were observed,inflammatory cell infiltration was obvious,the bile duct epithelial was hyperplasia and heterosexuality;in the Gehua Jiecheng group,the hepatocyte metamorphism,nodular

关 键 词：葛花解酲方 乙醇 乙型肝炎病毒 转基因小鼠 肝癌前病变 Wnt/β-连环蛋白 谷胱甘肽-S转移酶 增殖细胞核抗原 

分 类 号：R285.5[医药卫生—中药学]