益肾活血方通过调控TLR4/NF-κB信号通路对多发性骨髓瘤小鼠炎症反应及细胞免疫功能的影响

李宜真; 王栋范; 吴建伟

doi:10.16025/j.1674-1307.2025.07.011

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益肾活血方通过调控TLR4/NF-κB信号通路对多发性骨髓瘤小鼠炎症反应及细胞免疫功能的影响

实验研究 | 更新时间：2025-09-11

- 益肾活血方通过调控TLR4/NF-κB信号通路对多发性骨髓瘤小鼠炎症反应及细胞免疫功能的影响
- Effects of Yishen Huoxue Formula on inflammatory response and cellular immune function in mice with multiple myeloma by regulating TLR4/NF-κB signaling pathway
- 北京中医药 2025年44卷第7期页码：867-873
- 作者机构：
  
  1.广州市中西医结合医院肿瘤血液科，广州 510000
  2.江门市五邑中医院血液病科，江门 529000
- 作者简介：
  
  李宜真，女，40岁，硕士，主任医师。研究方向：中西医结合治疗血液病。
  吴建伟，E-mail：13570479083@163.com
- 基金信息：
  
  广东省基础与应用基础研究基金项目(2020A1515110616)
- DOI：10.16025/j.1674-1307.2025.07.011
  中图分类号：
- 收稿日期：2024-08-26，
  
  纸质出版日期：2025-07-25
- 稿件说明：
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李宜真，王栋范，吴建伟.益肾活血方通过调控TLR4/NF-κB信号通路对多发性骨髓瘤小鼠炎症反应及细胞免疫功能的影响［J］.北京中医药，2025，44（7）：867-873.

LI YiZhen,WANG DongFan,WU JianWei.Effects of Yishen Huoxue Formula on inflammatory response and cellular immune function in mice with multiple myeloma by regulating TLR4/NF-κB signaling pathway[J]. Beijing Journal of Traditional Chinese Medicine,2025,44(07):867-873.
李宜真，王栋范，吴建伟.益肾活血方通过调控TLR4/NF-κB信号通路对多发性骨髓瘤小鼠炎症反应及细胞免疫功能的影响［J］.北京中医药，2025，44（7）：867-873. DOI： 10.16025/j.1674-1307.2025.07.011.

LI YiZhen,WANG DongFan,WU JianWei.Effects of Yishen Huoxue Formula on inflammatory response and cellular immune function in mice with multiple myeloma by regulating TLR4/NF-κB signaling pathway[J]. Beijing Journal of Traditional Chinese Medicine,2025,44(07):867-873. DOI： 10.16025/j.1674-1307.2025.07.011.

摘要

目的

探讨益肾活血方通过调控Toll样受体4/核转录因子-κB（TLR4/NF-κB）信号通路对多发性骨髓瘤小鼠炎症反应及细胞免疫功能的影响。

方法

常规培养人源多发性骨髓瘤细胞系（RPM18226细胞）。采用随机数字表法将60只小鼠分为对照组、模型组、阳性对照组，及益肾活血方低、中、高剂量组，各10只。除对照组外，其余各组给予RPM18226细胞接种制备多发性骨髓瘤小鼠模型。益肾活血方低、中、高剂量组分别给予益肾活血方5、10、15 g/（kg·d）灌胃，阳性对照组给予罗格列酮5 mg/（kg·d）灌胃，模型组给予等体积生理盐水灌胃，1 次/d，连续给药30 d。比较各组腹水量和肿瘤体积，苏木素-伊红（HE）染色观察肿瘤组织病理变化，酶联免疫吸附试验（ELISA）检测血清炎症因子［白细胞介素（IL）6、肿瘤坏死因子（TNF）α）］，噻唑蓝溴化四氮唑（MTT）法检测脾脏组织B淋巴细胞、T淋巴细胞增殖，Western blotting法检测肿瘤组织中TLR4、NF-кB p65、p-NF-кB p65、IL-1β蛋白表达，实时荧光定量聚合酶链反应（qRT-PCR）检测肿瘤组织中TLR4、NF-кB、IL-1β mRNA表达。

结果

与对照组比较，模型组小鼠腹水量和肿瘤体积升高（

0.05）；与模型组比较，益肾活血方各剂量组和阳性对照组腹水量、肿瘤体积低（

0.05）；与益肾活血方低剂量组比较，益肾活血方中、高剂量组和阳性对照组腹水量、肿瘤体积低（

0.05）；与益肾活血方中剂量组比较，益肾活血方高剂量组和阳性对照组腹水量、肿瘤体积低（

0.05）。益肾活血方各剂量组和阳性对照组瘤体细胞逐渐减少，液化和坏死现象也逐渐消失。与对照组比较，模型组小鼠血清IL-6、TNF-α水平高，B淋巴细胞、T淋巴细胞增殖率低（

0.05）；与模型组比较，益肾活血方各剂量组和阳性对照组血清IL-6、TNF-α水平低，B淋巴细胞、T淋巴细胞增殖率高（

0.05）；与益肾活血方低剂量组比较，益肾活血方中、高剂量组和阳性对照组血清IL-6、TNF-α水平低，B淋巴细胞、T淋巴细胞增殖率高（

0.05）；与益肾活血方中剂量组比较，益肾活血方高剂量组和阳性对照组血清IL-6、TNF-α水平低，B淋巴细胞、T淋巴细胞增殖率高（

0.05）。与对照组比较，模型组肿瘤组织中TLR4、p-NF-кB p65、IL-1β蛋白表达高（

0.05）；与模型组比较，益肾活血方各剂量组和阳性对照组肿瘤组织中TLR4、p-NF-кB p65、IL-1β蛋白表达低

（

0.05）；与益肾活血方低剂量组比较，益肾活血方中、高剂量组和阳性对照组肿瘤组织中TLR4、p-NF-кB p65、IL-1β蛋白表达低（

0.05）；与益肾活血方中剂量组比较，益肾活血方高剂量组和阳性对照组肿瘤组织中TLR4、p-NF-кB p65、IL-1β蛋白表达低（

0.05）。与对照组比较，模型组肿瘤组织中TLR4、NF-кB p65、IL-1β mRNA表达高（

0.05）；与模型组比较，益肾活血方各剂量组和阳性对照组肿瘤组织中TLR4、NF-кB p65、IL-1β mRNA表达低（

0.05）；与益肾活血方低剂量组比较，益肾活血方中、高剂量组和阳性对照组肿瘤组织中TLR4、NF-кB p65、IL-1β mRNA表达低（

0.05）；与益肾活血方中剂量组比较，益肾活血方高剂量组和阳性对照组肿瘤组织中TLR4、NF-кB p65、IL-1β mRNA表达低（

0.05）。

结论

益肾活血方可有效改善多发性骨髓瘤小鼠炎症反应及细胞免疫功能，其机制可能与抑制TLR4/NF-κB信号通路有关。

Abstract

Objective

To investigate the effects of

Yishen Huoxue Formula

on the inflammatory response in multiple myeloma mice by regulating the Toll-like receptor 4/nuclear factor-κB （TLR4/NF-κB） signaling pathway.

Methods

Human multiple myeloma RPM18226 cells were routinely cultured. Sixty mice were randomly divided into six groups using a random number table：control group，model group，positive control group，and low-，medium-，and high-dose groups of

Yishen Huoxue Formula

，with 10 mice per group.Except for the control group，all other groups were inoculated with RPMI8226 cells to establish the multiple myeloma model.The low-，medium-，and high-dose groups received

Yishen Huoxue Formula

at 5，10，and 15 g/（kg·d） by gavage，respectively.The positive control group received rosiglitazone at 5 mg/（kg·d） by gavage.The model group received an equal volume of saline.All groups were treated once daily for 30 days.Ascites volume and tumor volume were measured. Histopathological changes were observed by hematoxylin-eosin（HE）staining.Serum inflammatory factors［interleukin（IL）-6 and tumor necrosis factor（TNF）-α］were detected by ELISA.B and T lymphocyte proliferation in the spleen was assessed by MTT assay.Protein expression of TLR4，NF-κB p65

，p-NF-κB p65，and IL-1β in tumor tissues was measured by Western blot，and mRNA expression of TLR4，NF-κB p65，and IL-1β was analyzed by quantitative real-time PCR（qRT-PCR）.

Results

Compared with the control group，the model group showed increased ascites and tumor volumes（

0.05）.Compared with the model group，

Yishen Huoxue Formula

groups and the positive control group showed decreased ascites and tumor volumes（

0.05）.Compared with the low-dose group of

Yishen Huoxue Formula

，the ascites volume and tumor volume in the medium-and high-dose groups of

Yishen Huoxue Formula

and the positive control group were lower（

0.05）.Compared with the medium-dose group of

Yishen Huoxue Formula

，the high-dose group of

Yishen Huoxue Formula

and the positive control group had lower ascites volume and tumor volume（

0.05）.Tumor cells in all dose groups and the positive control group gradually decreased，and liquefaction and necrosis disappeared.Serum IL-6 and TNF-α levels were elevated and B and T lymphocyte proliferation rates were reduced in the model group compared with the control group（

0.05）.All

Yishen Huoxue Formula

groups and the positive control group showed decreased serum IL-6 and TNF-α levels and increased B and T lymphocyte proliferation compared with the model group（

0.05）.Compared with the low-dose group of

Yishen Huoxue Formula

，the levels of serum IL-6 and TNF-α in the medium-and high-dose groups of

Yishen Huoxue Formula

and the positive control group were lower，and the proliferation rates of B lymphocytes and T lymphocytes were higher（

0.05）.Compared with the medium-dose group of

Yishen Huoxue Formula

，the levels of serum IL-6 and TNF-α in the high-dose group of

Yishen Huoxue Formula

and the positive control group were lower，and the proliferation rates of B lymphocytes and T lymphocytes were higher（

0.05）.Protein expression of TLR4，p-NF-κB p65，and IL-1β in tumor tissues was elevated in the model group compared with the control group（

0.05）and was reduced in all dose groups and the positive control group compared with the model group（

0.05）.Compared with the low-dose group of

Yishen Huoxue Formula

，the protein expression of TLR4，p-NF-κB p65，and IL-1β in the tumor tissues of the medium-dose and high-dose groups of

Yishen Huoxue Formula

and the positive control group was lower（

0.05）.Compared with the medium-dose group of

Yishen Huoxue Formula

，the protein expression of TLR4，p-NF-κB p65，and IL-1β in the tumor tissues of the high-dose group of

Yishen Huoxue Formula

and the positive control group was lower（

0.05）.Expression of TLR4，p-NF-κB p65，and IL-1β mRNA in tumor tissues was elevated in the model group compared with the control group（

0.05）and was reduced in all dose groups and the positive control group compared with the model group（

0.05）.Compared with the low-dose group of

Yishen Huoxue Formula

，the mRNA expression of TLR4，p-NF-κB p65，and IL-1β in the tumor tissues of the medium-dose and high-dose groups of

Yishen Huoxue Formula

and the positive control group was lowe（

0.05）.Compared with the medium-dose group of

Yishen Huoxue Formula

，the mRNA expression of TLR4，p-NF-κB p65，and IL-1β in the tumor tissues of the high-dose group of

Yishen Huoxue Formula

and the positive control group was lower（

0.05）.

Conclusion

Yishen Huoxue Formula

effectively improves inflammatory responses and cellular immune function in multiple myeloma mic

e， potentially through inhibition of the TLR4/NF-κB signaling pathway.

关键词

Keywords

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