补肾健脾方介导法尼醇X受体抑制肝癌细胞AH-130诱导大鼠恶病质的作用及其机制  

Effects of Bushen Jianpi formula on farnesoid X receptor-mediated inhibition of hepatocellular carcinoma AH-130 cell-induced cachexia in rats and its underlying mechanism

作　　者：冯思棋 钟薏 李诗颖 李芸 吴中华[2] 汤晓雯 周张杰 吴婷婷 FENG Siqi;ZHONG Yi;LI Shiying;LI Yun;WU Zhonghua;TANG Xiaowen;ZHOU Zhangjie;WU Tingting(Oncology Department of Shanghai TCM-Integrated Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Science and Technology Innovation Center,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;The Ministry of Education Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines,Institute of Chinese Materia Medica,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属上海市中西医结合医院肿瘤科,上海201203 [2]上海中医药大学科技创新中心,上海201203 [3]上海中医药大学中药研究所、中药标准化教育部重点实验室暨上海市复方中药重点实验室,上海201203

出　　处：《中国肿瘤生物治疗杂志》2024年第12期1204-1210,共7页Chinese Journal of Cancer Biotherapy

基　　金：2021年度“科技创新行动计划”扬帆计划项目(No.21YF1444400);2024年虹口区卫健委中医药科研课题(No.HKZYY-2024-24);虹口区第二轮“国医强优”三年行动计划(2022-2024)(No.HKGYQYXM-2022-10);上海市虹口区卫生健康委员会中医药科研课题(No.HKQGYQY-ZYY-2022-17);2019年上海市中西医结合医院科研课题(No.中西医18-01-02);上海中医药大学预算内项目(No.2019LK048)。

摘　　要：目的:探讨补肾健脾方(BSJP)介导法尼醇X受体(FXR)抑制肝癌细胞AH-130诱导的癌性恶病质(CC)大鼠模型的作用及其机制。方法:腹腔注射AH-130细胞建立肝癌CC大鼠模型,实验分为空白对照组、模型对照组、FXR激动剂(CDCA)组、BSJP组和BSJP+CDCA组。建模后,用CDCA、BSJP连续治疗大鼠16 d,每周称量大鼠体质量。实验结束时开腹,取腹主动脉血、粪便及附睾、腹股沟和肩胛区棕色脂肪质量。采用液相色谱-质谱法(LC-MS)检测大鼠血清和粪便中胆汁酸组分及含量,WB、qPCR法检测大鼠空肠、棕色及白色脂肪组织中FXR、Wnt家族成员10b(Wnt10b)、β-连环蛋白(β-catenin)、解偶联蛋白1(UCP-1)的表达。结果:与空白对照组相比,模型对照组大鼠体质量明显降低(P <0.01);与模型对照组相比,CDCA、BSJP、BSJP+CDCA组大鼠体质量均增加(均P <0.01)。与空白对照组相比,模型对照组附睾、腹股沟和肩胛区域及总棕色脂肪质量均上升(均P <0.05);与模型对照组相比,各治疗组大鼠附睾、腹股沟区、棕色脂肪质量均下降(均P <0.05),而肩胛区棕色脂肪组织质量下降无差异(P> 0.05);各治疗组总棕色脂肪质量均显著下降(P <0.05或P <0.01)。LC-MS分析显示,各组大鼠血清及粪便中胆汁酸组成及含量均发生改变。q PCR、WB法结果证实,与模型组相比,BSJP和BSJP+CDCA可促进大鼠回肠、棕色脂肪及白色脂肪组织中FXR mRNA和蛋白表达升高(均P <0.05),Wnt10b、β-catenin、UCP-1 mRNA和蛋白表达均下降(均P <0.05)。结论:BSJP能够抑制肝癌AH-130细胞诱导的大鼠CC,并减轻由此引起的体质量下降和棕色脂肪组织的形成,其机制可能涉及调控FXR并通过抑制棕色脂肪中与Wnt通路相关的Wnt10b、β-catenin和UCP-1的表达来实现。Objective:To investigate the effects of Bushen Jianpi formula(BSJP)in mediating the inhibitory effects of farnesoid X receptor(FXR)on cancer cachexia(CC)induced by hepatocellular carcinoma AH-130 cells in a rat model and its underlying mechanism.Methods:A liver cancer cachexia rat model was established by intraperitoneal injection of AH-130 cells.The rats were divided into five groups:blank control,model control,CDCA(FXR agonist),BSJP,and BSJP+CDCA groups.After modelling,the rats were treated with CDCA,BSJP,or their combination for consecutive 16 days,and their body weights were measured weekly.At the end of the experiment,the rats were sacrificed,and abdominal aortic blood,feces,and brown adipose tissues from the epididymal,inguinal,and scapular regions were collected.Liquid chromatography-mass spectrometry(LC-MS)was used to detect the composition and content of bile acids in serum and feces of rats.WB and qPCR were used to detect the expression of FXR,Wnt family member 10b(Wnt10b),β-catenin,and uncoupling protein 1(UCP-1)in the ileum,brown adipose,and white adipose tissues of rats.Results:Compared with the blank control group,the body mass of the rats in the model group was significantly reduced(P<0.01);compared with the model control group,the body mass of the rats in CDCA,BSJP and BSJP+CDCA groups all increased(P<0.01).Compared with the blank control group,the epididymal,inguinal,scapular,and total brown adipose tissue mass were all elevated in the model control group(all P<0.05);compared with the model control group,the brown fat mass in the inguinal and epididymis regions of the rats decreased significantly in all treatment groups(P<0.05),but this decrease was not significant in the scapular region(P>0.05);besides,the total brown fat mass decreased notably in all treatment groups compared to the model control group(all P<0.01).LC-MS analysis showed that the composition and content of bile acids in the serum and feces of rats were altered in all groups.qPCR and WB results confirmed that,compared to the mode

关 键 词：癌性恶病质 肝细胞癌 补肾健脾方 法尼醇X受体 棕色脂肪 

分 类 号：R735.7[医药卫生—肿瘤] R730.2[医药卫生—临床医学] R285.5