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
DOI:10.3872/j.issn.1007-385x.2024.12.005
- VernacularTitle: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
- Author:
FENG Siqia
1
;
ZHONG Yia
1
;
LI Shiyinga
1
;
LI Yuna
1
;
WU Zhonghuab
1
;
TANG Xiaowenc
1
;
ZHOU Zhangjiea
1
;
WU Tingtinga
1
Author Information
1. (a. Oncology Department of Shanghai TCM-Integrated Hospital; b. Science and Technology Innovation Center; c. 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)
- Publication Type:Journal Article
- Keywords:
癌性恶病质;肝细胞癌;补肾健脾方;法尼醇X受体;棕色脂肪
- From:
Chinese Journal of Cancer Biotherapy
2024;31(12):1204-1210
- CountryChina
- Language:Chinese
-
Abstract:
[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。qPCR、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。
- Full text:202502281045593231720241205.pdf