人胰腺癌恶病质小鼠模型的建立及特征研究  

Establishment and characterization of a nude mouse model of pancreatic cancer-induced cachexia

作　　者：徐康菁 王新颖 Xu Kangjing;Wang Xinying(Research Institute of General Surgery,Jinling Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing 210002,China)

机构地区：[1]南京大学医学院附属金陵医院普通外科研究所,210002

出　　处：《中华临床营养杂志》2023年第5期276-283,共8页Chinese Journal of Clinical Nutrition

基　　金：国家自然科学基金面上项目(82170575);国家自然科学基金面上项目(81770531);江苏省重点研发项目(BE2022822)。

摘　　要：目的建立可以体现胰腺癌恶病质主要特征的小鼠模型,研究其表型、代谢和恶病质相关分子表达变化。方法将裸鼠随机分为对照组(6只)和肿瘤组(6只)。肿瘤组裸鼠腹腔注射人胰腺癌细胞Panc01建立胰腺癌恶病质模型,密切记录其体重、食物摄入、抓力及体成分变化。2周后处死并解剖小鼠,观察腹腔内肿瘤转移情况。采用实时荧光定量聚合酶链式反应检测小鼠肌肉和脂肪组织中恶病质相关分子的基因表达情况,以及外周血中相关炎症因子表达情况。结果肿瘤组小鼠出现明显恶病质表型,表现为食物摄入、瘦体重和抓力减少,并在骨骼肌和心肌中观察到其肌肉分解代谢增强。出现下丘脑炎症反应,白色脂肪组织解偶联蛋白1表达增多,血液学结果异常,包括白细胞增多和贫血。结论人胰腺癌细胞Panc01腹腔注射裸鼠是研究胰腺癌恶病质的可靠模型,它再现了胰腺癌过程的关键特征,并诱导了广泛的恶病质表现。因此,该模型适合于探索胰腺癌恶病质相关生理系统的机制研究以及新疗法的临床前研究。Objective To establish a mouse model representing the cardinal features of pancreatic ductal adenocarcinoma-induced cachexia,and to investigate the changes in phenotype,metabolism and cachexia-related biomarkers.Methods BALB/c nude mice were randomly divided into control group(n=6)and tumor group(n=6).The cachexia model of pancreatic cancer was established in BALB/c nude mice by intraperitoneal injection of Panc01 cell line.The changes in body weight,food intake,grip strength and body composition were recorded over the course of tumor development.The animals were euthanized after 2 weeks and were examined for intraperitoneal metastasis.Quantitative real-time polymerase chain reaction was used to detect the expression of cachexia related genes in muscle and adipose tissue and the expression of related inflammatory factors in peripheral blood.Results The animals in tumor group showed an obvious cachexia phenotype,which was manifested by decreased food intake,lean body weight,and grip strength,and enhanced muscle catabolism.The wasting syndrome in this model was accompanied by hypothalamic inflammation and upregulated expression of uncoupling protein 1(Ucp1)in white adipose tissue.Haematological abnormalities included leukocytosis and anemia.Conclusions Intraperitoneal injection of human pancreatic cancer cell Panc01 into nude mice is a reliable model for the study of cachexia,which recapitulates the key features of the pancreatic cancer progress and induces a wide array of cachexia manifestations.Therefore,this model is suitable for preclinical researches exploring the mechanism of cachexia related to pancreatic cancer and identifying novel therapies.

关 键 词：胰腺癌 恶病质 小鼠模型 系统性炎症反应 分子表达 

分 类 号：R735.9[医药卫生—肿瘤] R-332[医药卫生—临床医学]