雷帕霉素对Yap1-β-连环蛋白诱导儿童肝母细胞瘤抑制作用的研究  

Effect of rapamycin on Yap1-β-Catenin induced hepatoblastoma in children

作　　者：任慧[1] 赵天娇 张娟 陈秀珍 刘锋[1] 牛会忠[1] REN Hui;ZHAO Tianjiao;ZHANG Juan;CHEN Xiuzhen;LIU Feng;NIU Huizhong(Department of General Surgery,Children's Hospital of Hebei Province,Shijiazhuang 050000,China)

机构地区：[1]河北省儿童医院普外科,河北石家庄050000

出　　处：《新疆医科大学学报》2021年第3期310-314,共5页Journal of Xinjiang Medical University

基　　金：2019年度河北省医学科学研究课题计划(20190132)。

摘　　要：目的探讨哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)抑制剂雷帕霉素(rapamycin,RAPA)影响转录共刺激因子-Yes相关蛋白(yes-associated protein,YAP)1-β-连环蛋白(β-catenin)诱导的儿童肝母细胞瘤(Hepatoblastoma,HB)生长发育的影响。方法采用尾静脉高压注射法制作Yap1-β-连环蛋白诱导HB小鼠模型,随机分为对照组和观察组。采用超声检测小鼠肝脏体积和HB肿瘤数量、直径,采用苏木精-伊红染色法(hematoxylin-eosin staining,HE染色)观察组织学变化。结果在注射后第4周时2组小鼠的肝脏体积[(783.7±48.2)mm^(3)vs(805.3±59.6)mm^(3)]、肿瘤数量[(0.3±0.9)个vs(0.5±0.8)个]和肿瘤直径[(0.5±2.6)mm vs(0.9±3.1)mm]差异均无统计学意义,在注射第10周末RAPA饮食组小鼠肝脏体积[(5963.7±1423.5)mm^(3)vs(1492.3±483.5)mm^(3)]、肿瘤数量[(19.4±11.2)个vs(40.3±8.5)个]和肿瘤直径[(179.3±34.6)mm vs(45.8±23.2)mm]均显著降低(P<0.05),TIR为72.69%。大体形态观察显示,对照组小鼠肝脏体积显著高于对照组。HE染色显示,对照组表现为低分化或未分化HB,观察组表现类似于高良好HB。免疫组化染色显示,观察组myc标签蛋白阳性HB结节数量明显减少。结论RAPA可抑制HB增殖,促使HB向分化良好的组织学形态发展。Objective To observe the effect of mammalian target of rapamycin(mTOR)inhibitor rapamycin(RAPA)on the growth and development of childhood hepatoblastoma(HB)induced by yAP-1-β-Catenin.Methods The model of HB mice induced by Yap1-β-Catenin was established by high pressure injection through tail vein,and the mice were randomly divided into control group and observation group.The volume of liver and the number and diameter of HB tumor were detected by ultrasound,and the histological changes were observed by hematoxylin eosin staining(HE staining).Results At 4 weeks after injection,there was no significant difference in liver volume[(783.7±48.2)mm^(3) vs(805.3±59.6)mm^(3)],tumor number[(0.3±0.9)tumors vs(0.5±0.8)tumors]and tumor diameter[(0.5±2.6)mm vs(0.9±3.1)mm]between the two groups.At the end of the 10 th week,the liver volume[(5963.7±1423.5)mm^(3) vs(1492.3±483.5)mm^(3)],tumor number[(19.4±11.2)tumors vs(40.3±8.5)tumors]and tumor diameter[(179.3±34.6)mm vs(45.8±23.2)mm]were significantly decreased in RAPA diet group.The TIR was 72.69%.Gross observation showed that the liver volume of the control group was significantly higher than that of the control group.HE staining showed that the control group showed poorly differentiated or undifferentiated HB,and the observation group was similar to high and good HB.Immunohistochemical staining showed that the number of myc tag protein positive HB nodules in the observation group was significantly reduced.Conclusion RAPA can inhibit the proliferation of HB and promote the development of well differentiated histological morphology of HB.

关 键 词：肝母细胞瘤 连环蛋白 哺乳动物雷帕霉素靶蛋白 雷帕霉素 

分 类 号：R735.7[医药卫生—肿瘤]