核因子-κB抑制剂调控癌性恶病质的实验研究  

Effect of nuclear factor-κB inhibitor on cancer cachexia

作　　者：佴永军[1] 江志伟[1] 汪志明[1] 黎介寿[1] 

机构地区：[1]南京大学医学院临床学院(南京军区南京总医院)解放军普通外科研究所,江苏南京210002

出　　处：《肠外与肠内营养》2007年第5期270-274,共5页Parenteral & Enteral Nutrition

摘　　要：目的:本研究旨在评价核因子-κB(NF-κB)抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)对C26恶病质小鼠炎性细胞因子的合成及对恶病质的调控作用。方法:采用雄性BALB/c小鼠皮下接种C26结肠癌细胞诱导恶病质模型,每天监测小鼠食物摄入量、体质量及肿瘤体积。于接种肿瘤后第7天开始,每天给予荷瘤鼠腹腔内注射等渗盐水及不同剂量的PDTC(10、50及100 mg/kg),第16天处死小鼠,检测血生化指标、血清及肿瘤组织中IL-6水平,肿瘤组织NF-κB活性。结果:荷瘤组小鼠出现明显的组织消耗,第16天去瘤体质量为正常小鼠的71.3%(P<0.01);腓肠肌及附睾脂肪重量分别减少42.4%和70.4%(P<0.01);血清清蛋白、葡萄糖及三酰甘油水平显著下降(P<0.01);血清及肿瘤组织IL-6水平显著升高(P<0.01)。PDTC呈剂量依赖性地抑制肿瘤组织NF-κB激活,抑制肿瘤组织IL-6的合成,抑制了去瘤体质量、腓肠肌及附睾脂肪的消耗,改善了恶病质。PDTC 100 mg/kg明显抑制肿瘤生长(P<0.05)。各组间食物摄入量无明显统计学差异。结论:PDTC通过抑制肿瘤组织NF-κB的激活,抑制炎性细胞因子的合成,从而改善了恶病质。Objective： To investigate the effect of pyrrolidine dithiocarbamate（PDTC） on IL-6 synthesis and cachexia in colon 26 tumor bearing mice.Methods： Male BALB/c mice bearing colon 26 adenocarcinoma were severed as a model of cancer cachexia.Saline and three doses of PDTC（10,50 or 100 mg/kg） were given intraperitoneally daily from 7 days after tumor inoculation to sacrifice.Body weight,food intake and tumor volume were monitored daily.Serum and tumor tissue levels of IL-6,serum biochemical indicator,and activity of NF-κB in tumor tissue were investigated in all animals. Results： Significant tissue wasting was observed in all tumor-bearing mice.By day 16,carcass weights of untreated tumor-bearing mice were about 71.3% of healthy controls（P〈0.01）,and the weights of gastrocnemius muscle and epididymal fat were lowered by 42.4% and 70.4%（P〈0.01）,respectively.Furthermore,tumor-bearing state caused a significant decrease of serum albumin,glucose and triglyceride（P〈0.01）,and increase of IL-6（P〈0.01） in serum and tumor tissues.Administration of PDTC dose dependently inhibited the NF-κB activation in tumor tissues,inhibited IL-6 synthesis of the tumor cells,and attenuated the wasting of carcass weight,gastrocnemius muscle and epididymal fat.Tumor growth was inhibited by PDTC with 100 mg/kg（P〈0.05）.No differences of food intake were found between groups（P〉0.05）.Conclusion： PDTC can attenuate the development of cachexia in colon 26 tumor bearing mice through inhibition of IL-6 synthesis regulated by NF-κB.

关 键 词：吡咯烷二硫代氨基甲酸盐 核因子-ΚB 恶病质 白细胞介素-6 

分 类 号：R730.5[医药卫生—肿瘤]