去唾液酸糖蛋白受体(ASGPR)在N-二硝基亚乙胺诱导原位肝癌模型、原位移植肝癌模型大鼠体内的表达与分布  

Expression and distribution of asialoglycoprotein receptor(ASGPR) in N-dinitroethylamine-induced hepatocellular carcinoma model and orthotopic transplantation tumor mode in rats

作　　者：杨文川 张发斌[1] 胡春晖[1] 孔宪梅 都涛 赵振文 YANG Wenchuan;ZHANG Fabin;HU Chunhui;KONG Xianmei;DU Tao;ZHAO Zhenwen(Medical College of Qinghai University,Xining 810001,China;Center for Molecular Imaging and Translational Medicine,Xiamen University,Xiamen 361000,China)

机构地区：[1]青海大学医学院,青海西宁810001 [2]厦门大学公共卫生学院分子影像暨转化医学研究中心,福建厦门361000

出　　处：《药物评价研究》2024年第2期302-308,共7页Drug Evaluation Research

基　　金：2022年中科院“西部之光”人才培养计划。

摘　　要：目的 测定去唾液酸糖蛋白受体(ASGPR)在N-二硝基亚乙胺(DEN)诱导大鼠原位肝癌模型(DEN-HCC-Rat)和原位移植大鼠肝癌模型(OTT-HCC-Rat)中的表达。方法 DEN-HCC-Rat造模:模型组SD大鼠按照20 mg·kg^(-1) ig 0.25%DEN水溶液,每周1次,0.025%DEN水溶液供动物饮用;对照组每周ig 1次0.9%氯化钠溶液,灭菌水供动物饮用,于造模第4、10、18、22周取材。OTT-HCC-Rat造模:模型组SD大鼠肝叶注射N1-S1细胞,假手术组大鼠麻醉后给予微创缝合处理,于注射后14 d取材。HE染色观察肝组织病变;通过免疫组化、免疫荧光、Western blotting和实时荧光定量PCR(qRT-PCR)实验检测各组ASGPR表达及分布。结果 通过HE染色确定DEN-HCC-Rat和OTT-HCC-Rat造模成功。在DEN-HCC-Rat中,免疫组化、免疫荧光、Western blotting、qRT-PCR结果均显示,与对照组比较,模型组大鼠肝组织ASGPR表达显著上调(P<0.05、0.01),且呈时间相关性;在OTT-HCC-Rat中,免疫组化结果显示模型组ASGPR表达显著高于假手术组(P<0.05),免疫荧光、Western blotting、qRT-PCR结果显示ASGPR在模型组与假手术组之间无显著性差异。结论DEN-HCC-Rat模型更好地模拟肿瘤微环境改变,且ASGPR在肝癌区域表达高于对照组大鼠肝脏,故可利用ASGPR介导肝靶向制剂的转运,提高肝靶向药物治疗效果。Objective To determine the role of asialoglycoprotein receptor(ASGPR) in N-dinitroethylamine(DEN)-induced hepatocellular carcinoma model in rats(DEN-HCC-Rat) and orthotopic transplantation tumor mode in rats(OTT-HCC-Rat).Methods DEN-HCC-Rat modeling:SD rats in the model group were ig given a 0.25% DEN aqueous solution of 20 mg·kg^(-1),once a week,with 0.025% DEN aqueous solution for animal consumption;The control group received 0.9% sodium chloride solution once a week,sterilized water for animal consumption,and samples were taken at weeks 4,10,18,and 22 of modeling.OTT-HCC-Rat modeling:SD rats in the model group were injected with N1-S1 cells into the liver lobes,while rats in the sham surgery group were anesthetized and treated with minimally invasive suturing.Samples were taken 14 days after injection.HE staining was used to observe liver tissue lesions.Immunohistochemistry,immunofluorescence,Western blotting and real-time fluorescent quantitative PCR(qRT-PCR) were used to detect the expression and distribution in the liver tissue of two orthotopic liver cancer rat models and normal rats.Results In DEN-HCC-Rat,immunohistochemistry,immunofluorescence,Western blotting,and qRT-PCR results all showed that compared with the control group,the ASGPR expression in the liver tissue of the model group rats was significantly upregulated(P < 0.05,0.01),and showed a time correlation.In OTT-HCC-Rat,immunohistochemistry results showed that the expression of ASGPR in the model group was significantly higher than that in the sham surgery group(P < 0.05).Immunofluorescence,Western blotting,and qRT-PCR results showed no significant difference in ASGPR between the model group and the sham surgery group.Conclusion The DEN-HCC-Rat model can better simulate the changes of tumor microenvironment and the expression of ASGPR in liver cancer is higher than that in normal rat liver.Therefore,ASGPR can be used to mediate the transport of liver targeted agents and improve the therapeutic effect of liver targeted drugs.

关 键 词：去唾液酸糖蛋白受体 N-二硝基亚乙胺 大鼠诱导原位肝癌模型 大鼠移植肝癌模型 靶向 

分 类 号：R965.2[医药卫生—药理学]