[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。

[Abstract] 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 model group, BSJP and BSJP + CDCA promoted the mRNA and protein expression of FXR in the ileum, brown adipose, and white adipose tissues of rats (all P < 0.05), and decreased the mRNA and protein expression of Wnt10b, β-catenin, UCP-1 (all P < 0.05). Conclusion: The BSJP formula can inhibit hepatocellular carcinoma cell AH-130-induced cachexia in rats, alleviating the associated body weight loss and brown adipose tissue formation. The mechanism may involve the regulation of FXR and the inhibition of the expression of Wnt10b, β -catenin, and UCP-1 in brown adipose tissue through the Wnt signaling pathway.

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-ZYY2022-17）；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）