目的 探讨补地参连方抑制 Janus 激酶（JAK）/信号转导与转录激活因子（STAT）信号通路调控肿瘤相关巨 噬细胞极化抗结直肠癌的作用机制。方法 将 42 只 BALB/c 小鼠随机分为空白对照组、模型组、5-氟尿嘧啶 组（5-FU，0.025 g·kg-1 ）及补地参连方低、中、高剂量组（10.98、21.97、43.94 g·kg-1 ），每组 7 只。观察小鼠体 质量、瘤体体积、肝肾指数、苏木精-伊红（HE）染色等指标。流式细胞术检测肿瘤组织中 M1、M2 型肿瘤相关 巨噬细胞（TAMs）标志物；采用酶联免疫吸附试验（ELISA）检测血清及组织内 TAMs 相关炎症因子水平，包括白 细胞介素（IL）-1β、IL-6、转化生长因子 β（TGF-β）；免疫组织化学染色法检测小鼠肿瘤组织中 p-JAK2、pSTAT3 蛋白表达；蛋白免疫印迹法（Western Blot）检测补地参连方干预后小鼠肿瘤组织内分化簇 86（CD86）、甘 露糖受体（CD206）、p-JAK2/JAK2、p-STAT3/STAT3 蛋白表达水平的变化；实时荧光定量聚合酶链式反应 （qPCR）检测肿瘤组织 CD86、CD206、JAK2、STAT3 基因表达含量。结果 与模型组比较，补地参连方能够抑 制小鼠皮下移植瘤的生长（P＜0.05，P＜0.01，P＜0.001），使肿瘤组织坏死程度增加，病理性核分裂像减少。 与空白组比较，模型组小鼠血清中 IL-6、IL-1β 含量显著降低（P＜0.001，P＜0.000 1），TGF-β 含量显著升高 （P＜0.000 1）；与模型组比较，5-FU 组及补地参连方各剂量组的血清及肿瘤组织中 IL-6、IL-1β 水平显著升 高（P＜0.05，P＜0.01，P＜0.001，P＜0.000 1），TGF-β 水平显著下降（P＜0.05，P＜0.01，P＜0.001，P＜ 0.000 1）。与模型组比较，各给药组肿瘤组织内 CD86 蛋白及 mRNA 表达升高（P＜0.05，P＜0.01，P＜0.001， P＜0.000 1），CD206、p-JAK2、JAK2、p-STAT3、STAT3 蛋白及 mRNA 表达降低（P＜0.05，P＜0.01，P＜ 0.001，P＜0.000 1）。结论 补地参连方对结直肠癌具有明显的抑制作用，并能通过调控 JAK/STAT 信号通路 影响结直肠癌 TAMs 向 M1 型巨噬细胞极化进程。

Objective To investigate the mechanism of Budishenlian Formula （mainly composed of Psoraleae Fructus， Rehmanniae Radix，Ginseng Radix et Rhizoma，Coptidis Rhizoma，etc.） in inhibiting colorectal cancer by regulating tumor-associated macrophages （TAMs） polarization through suppression of the Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway. Methods Forty-two BALB/c mice were randomly divided into a blank control group，a model group，a 5-fluorouracil （5-FU，0.025 g·kg-1 ） group，and low-，medium-，and high-dose Budishenlian Formula groups （10.98，21.97，43.94 g·kg-1 ），with 7 mice per group. The inhibitory effect of Budishenlian Formula on mouse subcutaneous xenograft tumors was assessed by observing body mass，tumor volume， liver and kidney indices，and hematoxylin-eosin （HE） staining. Flow cytometry was used to detect markers of M1 and M2 type TAMs in tumor tissue. Enzyme-linked immunosorbent assay （ELISA） was performed to measure serum and tissue levels of TAM-related inflammatory factors， including interleukin （IL）-1β， IL-6， and transforming growth factor-β（TGF-β）. Immunohistochemical staining was used to detect the expression of p-JAK2 and p-STAT3 proteins in mouse tumor tissue. Western Blot analysis was conducted to detect changes in protein expression levels of cluster of differentiation 86（CD86），mannose receptor （CD206），p-JAK2/JAK2，and p-STAT3/STAT3 in mouse tumor tissue after Budishenlian Formula intervention. Real-time quantitative polymerase chain reaction （qPCR） was used to measure the mRNA expression levels of CD86，CD206，JAK2，and STAT3 in tumor tissue. Results Compared with the model group，Budishenlian Formula inhibited the growth of subcutaneous xenograft tumors （P＜0.05，P＜0.01，P＜0.001）， increased the degree of necrosis in tumor tissue， and reduced pathological mitotic figures. Compared with the blank control group，serum levels of IL-6 and IL-1β were significantly decreased （P＜0.001，P＜0.000 1），while TGF-β levels were significantly increased （P＜0.000 1） in the model group. Compared with the model group，both the 5-FU group and the Budishenlian Formula dose groups showed significantly increased levels of IL-6 and IL-1β（P＜0.05， P＜0.01，P＜0.001，P＜0.000 1） and significantly decreased levels of TGF-β（P＜0.05，P＜0.01，P＜0.001，P＜ 0.000 1） in serum and tumor tissue. Compared with the model group，the treatment groups showed increased protein and mRNA expression of CD86 （P＜0.05， P＜0.01， P＜0.001， P＜0.000 1）， and decreased protein and mRNA expression of CD206，p-JAK2，JAK2，p-STAT3，and STAT3（P＜0.05，P＜0.01，P＜0.001，P＜0.000 1） in tumor tissue. Conclusion Budishenlian Formula exhibits significant inhibitory effects on colorectal cancer and may influence the polarization of TAMs towards the M1 phenotype in colorectal cancer by regulating the JAK/STAT signaling pathway.

R285.5

国家自然科学基金面上项目（81973737）；江苏省中医药科技发展项目重点项目（ZD202301）；第二届全国名中医工作室建设项目 （国中医药人教函 〔2022〕 245号）；吴勉华全国名老中医药专家传承工作室建设项目（国中医药人教函 〔2022〕 75号）；吴勉华江苏省名老中医药 专家传承工作室建设项目（苏中医科教 〔2021〕 7 号）；江苏省研究生科研与实践创新计划项目（KYCX24_2247）；南京中医药大学自然科学 基金项目（XZR2024167）。