豨莶丸治疗类风湿关节炎的分子机制：基于蛋白质组学

doi:10.12122/j.issn.1673-4254.2025.11.05

南方医科大学学报 ›› 2025, Vol. 45 ›› Issue (11): 2330-2339.doi: 10.12122/j.issn.1673-4254.2025.11.05

豨莶丸治疗类风湿关节炎的分子机制：基于蛋白质组学

李亚辉¹(), 杨欣²^,⁴(), 姚血明³, 黄聪²^,³

^1.贵州中医药大学，信息工程学院，贵州贵阳 550025
^2.贵州中医药大学，基础医学院，贵州贵阳 550025
^3.贵州中医药大学，第二附属医院，贵州贵阳 550025
^4.贵州省高等学校中药（民族药）药性与效应研究重点实验室，贵州贵阳 550025

收稿日期:2025-03-05 出版日期:2025-11-20 发布日期:2025-11-28
通讯作者: 杨欣 E-mail:3844639309@qq.com;25066640@qq.com
作者简介:李亚辉，博士，讲师，E-mail: 3844639309@qq.com
基金资助:
贵州省科技厅贵州省基础研究计划项目（黔科合基础-ZK[2024]一般358）;贵州中医药大学国家与省级科技创新人才团队培育项目(贵中医TD合字[2022]004号)

Molecular mechanism of Xixian Pills for improving rheumatoid arthritis in rats: a proteomic analysis

Yahui LI¹(), Xin YANG²^,⁴(), Xueming YAO³, Cong HUANG²^,³

^1.School of Information Engineering, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
^2.School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
^3.Second Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
^4.Key Laboratory of Properties and Effects of Traditional Chinese Medicine (Ethnic Medicine) of Guizhou Province, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China

Received:2025-03-05 Online:2025-11-20 Published:2025-11-28
Contact: Xin YANG E-mail:3844639309@qq.com;25066640@qq.com

摘要/Abstract

摘要：

目的基于蛋白质组学分析豨莶丸（XXW）治疗类风湿关节炎（RA）的分子机制。方法复制大鼠胶原诱导关节炎模型，48只大鼠适应环境后随机分为6组（8只/组），造模成功2周后灌胃豨莶丸进行干预，豨莶丸低、中、高剂量换算后灌胃给药分别为200、400、800 mg/kg，雷公藤多苷片（LGTDGP）9 mg/kg，1次/d。正常对照组和模型对照组灌胃等体积 1% 羧甲基纤维素钠，连续灌胃给药3周。采用ELISA试剂盒测定大鼠血清中IL-10、IL-6、TNF-α 的含量。基于串联质谱标签（TMT）技术筛选豨莶丸高剂量组与模型组间的差异表达蛋白，通过R软件分析核心靶标及信号通路。基于ggplot2、tidyverse 等数据处理与可视化包，对免疫细胞浸润数据及相关基因表达数据进行整合处理，计算核心靶点与各类免疫细胞（如 T 细胞、B 细胞、巨噬细胞等）的相关性。采用免疫组化和免疫荧光验证核心靶点的表达情况。结果与正常对照组比较，模型组大鼠血清中TNF-α、IL-6的含量明显升高（P<0.01），IL-10含量降低（P<0.01）；与模型组比较，雷公藤多苷片、豨莶丸高剂量、中剂量组大鼠血清中TNF-α、IL-6的含量降低（P<0.01，P<0.05），IL-10含量增加（P<0.05，P<0.01）。蛋白质组学分析发现模型组和豨莶丸高剂量组交集出160个差异蛋白，趋化因子（CCL5），信号转导与转录激活因子1（STAT1），颗粒酶 B （GZMB）和白介素7受体（IL7R）为核心靶点。CCL5、STAT1的ROC曲线下面积大于0.9。4个核心靶点（CCL5，STAT1、GZMB、IL7R）与中央记忆 CD4 T细胞、效应记忆CD4 T细胞、骨髓源性抑制细胞等呈正相关（P<0.05）。免疫组化及免疫荧光分析发现，与空白对照组比较，模型组大鼠踝关节中CCL5、STAT1蛋白表达水平升高（P<0.01）；与模型组比较，经豨莶丸治疗后CCL5、STAT1蛋白表达水平降低（P<0.01）。结论豨莶丸对CIA大鼠具有关节保护作用，通过降低血清中促炎因子IL-6、TNF-α的含量，同时升高抗炎因子IL-10的水平，减轻炎症反应，其机制与调控CCL5，STAT1等蛋白的表达相关。

关键词: 豨莶丸, 类风湿关节炎, 蛋白质组学, 免疫细胞浸润

Abstract:

Objective To analyze the molecular mechanism of Xixian Pills for treatment of rheumatoid arthritis (RA). Methods Forty-eight rats were randomized into 6 groups (n=8), including a normal control group, a collagen-induced arthritis (CIA) model group, 3 Xixian Pills treatment (200, 400 and 800 mg/kg) groups, and a Tripterygium glycosides tablet (TGT) treatment group. In the latter 4 groups, the rats were treated with daily gavage of Xixian Pills or TGT 2 weeks after CIA modeling for 3 consecutive weeks. The differentially expressed proteins in high-dose Xixian Pills group and the model group compared with the normal control group were screened based on the tandem mass spectrometry tag (TMT) technology, and the core targets and signaling pathways were analyzed. The immune cell infiltration and gene expression data were analyzed using ggplot2 and tidyverse packages, and the correlation coefficients between the core targets and the immune cells were calculated. Results The CIA rats showed significantly increased serum levels of TNF-α and IL-6 and lowered serum IL-10 level. Treatments with high- and medium-dose Xixian Pills and TGT all significantly reduced serum TNF‑α and IL-6 and increased IL-10 levels in CIA rats. Proteomic analysis identified 160 differential proteins between the model group and high-dose Xixian Pills group, and the core targets included CCL5, STAT1, GZMB and IL7R. The areas under the ROC curve of CCL5 and STAT1 were both greater than 0.9. Immunohistochemical and immunofluorescence staining revealed increased levels of CCL5 and STAT1 in the ankle joints of CIA rats, which were significantly decreased after treatment with Xixian Pills. Conclusion Treatment with Xixian Pills offers protection of the joints in CIA rats possibly by inhibiting joint inflammation via regulating protein expressions of CCL5 and STAT1.

Key words: Xixian Pills, rheumatoid arthritis, proteomics, immune cell infiltration

李亚辉, 杨欣, 姚血明, 黄聪. 豨莶丸治疗类风湿关节炎的分子机制：基于蛋白质组学[J]. 南方医科大学学报, 2025, 45(11): 2330-2339.

Yahui LI, Xin YANG, Xueming YAO, Cong HUANG. Molecular mechanism of Xixian Pills for improving rheumatoid arthritis in rats: a proteomic analysis[J]. Journal of Southern Medical University, 2025, 45(11): 2330-2339.

图/表 13

表1 实验仪器设备及其来源

Tab.1 Experimental instruments and equipment and their sources

Experimental equipment	Model	Company
Nanoscale liquid chromatography instrument	EASY-nLC	Thermo fisher scientific
Ultrasonic disrupter	JY96-IIN	Ningbo xinzhi
Low-temperature high-speed centrifuge	5430R	Eppendorf
Vortex oscillator	G-560E	Scientific industries
Thermostatic incubator	GNP-9080	Shanghai jinghong
Mass spectrometer	Orbitrap Exploris 480	Thermo fisher scientific
Vacuum centrifuge concentrator	LNG-T98	Taicang huamei
Ultraviolet spectrophotometer	260 Bio	Thermo fisher scientific
High-performance liquid chromatography	1260 infinity II	Agilent technologies, inc.
Nano Drop	ND3000	Thermo fisher scientific

表2 踝关节肿胀度、炎性因子水平

Tab.2 Ankle joint swelling degree and inflammatory factor levels in the rats in different groups

Group	Ankle joint swelling degree	TNF-α (pg/L)	IL-6 (pg/L)	IL-10 (pg/L)
Control	0.229±0.016	54.86±7.4	38.94±8.6	55.32±3.6
Model	0.364±0.012**	144.68±10.2**	77.34±12.4**	22.62±6.1**
LGTDGP	0.243±0.015^##	62.32±10.3^##	45.63±11.3^##	46.24±7.6^#
XXW-H	0.268±0.017^##	70.24±9.6^##	55.24±7.7^##	47.35±5.8^##
XXW-M	0.291±0.016^#	98.63±12.4^#	59.24±14.3^#	38.36±8.7^#
XXW-L	0.324±0.021	125.34±18.9	69.34±9.7	30.24±9.6

图1 HE染色观察各大鼠踝关节组织病理学变化

Fig.1 Histopathological changes of the ankle joint tissues of the rats (HE staining, original magnification: ×100).

图2 差异表达蛋白及核心靶点分析

Fig.2 Analysis of differentially expressed proteins and core targets in rats with collagen-induced arthritis (CIA) and Xinxian Pills-treated rats. A: Volcano plot of the differential proteins. B: Intersection of the differential proteins between the CIA model group and the high-dose Xixian Pills group. C: Interaction analysis of the differential proteins.

表3 差异基因通路分析

Tab.3 Differential gene pathway analysis

NO. Path name

Gene count P

FDR

Primary immunodeficiency

Hematopoietic cell lineage

Cytokine-cytokine receptor interaction

Th17 cell differentiation

Epstein-Barr virus infection

Osteoclast differentiation

Th1 and Th2 cell differentiation

Human T-cell leukemia virus 1 infection

Viral protein interaction with cytokine and cytokine receptor

Breast cancer

2.57E-10

1.34E-08

3.06E-08

3.33E-08

5.84E-08

5.47E-07

9.08E-07

1.24E-06

1.57E-05

6.57E-05

3.62E-08

9.43E-07

1.18E-06

1.65E-06

1.29E-05

1.83E-05

2.19E-05

0.0002

0.0005

图3 CCL5、STAT1、GZMB和IL7R差异表达基因ROC分析

Fig.3 ROC analysis of the differentially expressed genes CCL5, STAT1, GZMB, and IL7R.

表4 CCL5、STAT1阳性细胞记数及免疫组化评分（5个视野）

Tab.4 Counts of CCL5- and STAT1-positive cells in rat ankle joint tissues and immunohistochemical scores （5 fields）

Group	CCL5(%)	CCL5 B	STAT1(%)	STAT1 B
Control	12±3.1	1	13±3.2	1
Model	50±2.5**	3	49±2.5**	3
LGTDGP	23±2.5^##	2	22±2.0^##	2
XXW-H	30±2.5^##	2	33±2.5^##	2

图4 各组大鼠踝关节中CCL5的表达

Fig.4 Expression of CCL5 in the ankle joints of the rats in each group (×200). A: Normal control group. B: Model group. C: Tripterygium glycosides tablet group. D: High-dose Xixian pill group.

图5 各组大鼠踝关节中STAT1的表达

Fig.5 Expression of STAT1 in the ankle joints of the rats in each group (×200). A: Normal control group. B: Model group. C: Tripterygium glycosides tablet group. D: High-dose Xixian pill group.

表5 CCL5、STAT1免疫荧光图像光密度分析（5个视野）

Tab.5 Optical density analysis of CCL5 and STAT1 on immunofluorescence staining images (5 fields)

Group	CCL5 (IOD)	CCL5(AOD)	STAT1 (IOD)	STAT1(AOD)
Control	2804.89±222.73	0.22±0.02	2097.43±403.42	0.17±0.03
Model	13661.38±145.47**	0.82±0.01**	12904.86±720.16**	0.78±0.05**
LGTDGP	6487.84±228.86^##	0.42±0.01^##	6693.79±120.62^##	0.43±0.04^##
XXW-H	9687.52±253.10^##	0.60±0.02^##	9398.39±624.72^##	0.59±0.03^##

图6 免疫荧光检测大鼠踝关节组织中CCL5的表达

Fig.6 Immunofluorescence detection of CCL5 expression in rat ankle joint tissue (×200). Green fluorescence indicates CCL5, while blue fluorescence indicates the cell nucleus (Scale bar=50 μm).

图7 免疫荧光检测大鼠踝关节组织中STAT1的表达

Fig.7 Immunofluorescence detection of STAT1 expression in rat ankle joint tissue (×200). Green fluorescence indicates STAT1, and blue fluorescence indicates the cell nucleus (Scale bar=50 μm).

图8 核心靶点与免疫细胞浸润之间的关系

Fig.8 Relationship between the core targets and immune cell infiltration. *P<0.05, **P<0.01, ***P<0.001.

参考文献 30

[1]	Wang GY, Zhang SL, Wang XR, et al. Remission of rheumatoid arthritis and potential determinants: a national multi-center cross-sectional survey[J]. Clin Rheumatol, 2015, 34(2): 221-30. doi：10.1007/s10067-014-2828-3
[2]	Jin SY, Li MT, Fang YF, et al. Chinese registry of rheumatoid arthritis (CREDIT): II.prevalence and risk factors of major comorbidities in Chinese patients with rheumatoid arthritis[J]. Arthritis Res Ther, 2017, 19(1): 251. doi：10.1186/s13075-017-1457-z
[3]	Safiri S, Kolahi AA, Hoy D, et al. Global, regional and national burden of rheumatoid arthritis 1990-2017: a systematic analysis of the Global Burden of Disease study 2017[J]. Ann Rheum Dis, 2019, 78(11): 1463-71. doi：10.1136/annrheumdis-2019-215920
[4]	Rudan I, Sidhu S, Papana A, et al. Prevalence of rheumatoid arthritis in low- and middle-income countries: a systematic review and analysis[J]. J Glob Health, 2015, 5(1): 010409.
[5]	Tsai SW, Hsieh MC, Li S, et al. Therapeutic potential of sclareol in experimental models of rheumatoid arthritis[J]. Int J Mol Sci, 2018, 19(5): E1351. doi：10.3390/ijms19051351
[6]	Liu XY, Dawson SL, et al. Isobaric tagging and data independent acquisition as complementary strategies for proteome profiling on an orbitrap astral mass spectrometer[J]. J Proteome Res, 2025, 24(3): 1414-24. doi：10.1021/acs.jproteome.4c01107
[7]	Burton NR, Backus KM. Functionalizing tandem mass tags for streamlining click-based quantitative chemoproteomics[J]. Commun Chem, 2024, 7(1): 80. doi：10.1038/s42004-024-01162-x
[8]	Huang LX, Liang L, Ji ZY, et al. Proteomics profiling of CD4⁺T-cell-derived exosomes from patients with rheumatoid arthritis[J]. Int Immunopharmacol, 2023, 122: 110560. doi：10.1016/j.intimp.2023.110560
[9]	Wang Q, Liang YY, Li KW, et al. Herba Siegesbeckiae: a review on its traditional uses, chemical constituents, pharmacological activities and clinical studies[J]. J Ethnopharmacol, 2021, 275: 114117. doi：10.1016/j.jep.2021.114117
[10]	胡慧华. 豨莶丸的配方优化及对实验性膝骨关节炎的药效及作用机理探讨[D]. 北京: 北京中医药大学, 2005.
[11]	向珊, 张宗星, 江露, 等. 三百棒通过调控PI3K/Akt信号通路改善胶原诱导性类风湿性关节炎大鼠的血管翳[J].南方医科大学学报,2024, 44(8): 1582-8.
[12]	夏俊锋, 杨全伟, 刘新国, 等. 豨莶草对大鼠佐剂型关节炎的治疗作用及机制研究[J]. 中国药师, 2021, 24(2): 242-6.
[13]	Xiao B, Li J, Qiao Z, et al. Therapeutic effects of Siegesbeckia orientalis L. and its active compound luteolin in rheumatoid arthritis: network pharmacology, molecular docking and experim-ental validation[J]. J Ethnopharmacol, 2023, 317: 116852. doi：10.1016/j.jep.2023.116852
[14]	郑梓桐, 王美娟, 冯育林, 等. 基于蛋白质组学筛选关节炎相关生物标志物的研究进展[J]. 中草药, 2024, 55(18): 6383-92.
[15]	Hsiao Y, Zhang HJ, Li GX, et al. Analysis and visualization of quantitative proteomics data using FragPipe-analyst[J]. J Proteome Res, 2024, 23(10): 4303-15. doi：10.1021/acs.jproteome.4c00294
[16]	Hou YW, Yang ZC, Ma JS, et al. Identification of PTPRC as a potential serum biomarker in rheumatoid arthritis using bioinfo-rmatics analysis and molecular docking[J]. Int Immunopharmacol, 2025, 152: 114393. doi：10.1016/j.intimp.2025.114393
[17]	Hu HH, Tang LX, Li XM. Experimental research of effect of crude and processed Herba Siegesbeckiae on anti-inflammation and anti-rheumatism[J]. Zhongguo Zhong Yao Za Zhi, 2004, 29(6): 542-5.
[18]	Wang J, Cai Y, Wu Y. Antiinflammatory and analgesic activity of topical administration of Siegesbeckia pubescens [J]. Pak J Pharm Sci, 2008, 21(2): 89-91.
[19]	Liu JH, Qu B, Wang S, et al. Fengshi gutong capsules attenuates CIA-induced RA bone destruction in rats by targeting TNF‑α inhibition: Integration and experimental validation of network pharmacology and proteomics[J]. J Ethnopharmacol, 2025, 344: 119535. doi：10.1016/j.jep.2025.119535
[20]	Suda Y, Ikuta K, Hayashi S, et al. Comparison of anti-inflammatory and anti-angiogenic effects of JAK inhibitors in IL-6 and TNF-α-stimulated fibroblast-like synoviocytes derived from patients with RA[J]. Sci Rep, 2025, 15(1): 9736. doi：10.1038/s41598-025-94894-2
[21]	Peilin Z, Wenqiang W, Yongzhen L, et al. Inflammatory cytokines, metabolites, and rheumatoid arthritis[J]. Postgrad Med J, 2025, 101(1194): 313-20. doi：10.1093/postmj/qgae146
[22]	Liu Y, Li L, Sun Y, et al. Dictamnus dasycarpus Turcz. Attenuates collagen-induced rheumatoid arthritis in DBA/1J mice through inhibiting IL-17 signaling pathway[J]. J Ethnopharmacol, 2025, 343: 119458. doi：10.1016/j.jep.2025.119458
[23]	Hinrichs AC, Blokland SLM, Kruize AA, et al. CCL5 release by CCR9+ CD8 T cells: a potential contributor to immunopathology of primary sjögren's syndrome[J]. Front Immunol, 2022, 13: 887972. doi：10.3389/fimmu.2022.887972
[24]	Alturaiki W, Alhamad A, Alturaiqy M, et al. Assessment of IL-1β, IL-6, TNF-α, IL-8, and CCL 5 levels in newly diagnosed Saudi patients with rheumatoid arthritis[J]. Int J Rheum Dis, 2022, 25(9): 1013-9. doi：10.1111/1756-185x.14373
[25]	Liang Q, He L, Wang JW, et al. Targeting IL-17 and its receptors: a feasible way for natural herbal medicines to modulate fibroblast-like synoviocytes in rheumatoid arthritis[J]. Biochem Pharmacol, 2024, 230: 116598. doi：10.1016/j.bcp.2024.116598
[26]	Cacciapaglia F, Perniola S, Stano S, et al. Modulation of IL-6 receptor/STAT3 downstream signaling in rheumatoid arthritis patients[J]. Exp Mol Pathol, 2025, 141: 104951. doi：10.1016/j.yexmp.2024.104951
[27]	Aubert A, Liu A, Kao M, et al. Granzyme B cleaves tenascin-C to release its C-terminal domain in rheumatoid arthritis[J]. JCI Insight, 2024, 9(23): e181935. doi：10.1172/jci.insight.181935
[28]	Zhang Y, Cai X, Wang B, et al. Exploring the molecular mechanisms of the involvement of GZMB-Caspase-3-GSDME pathway in the progression of rheumatoid arthritis[J]. Mol Immunol, 2023, 161: 82-90. doi：10.1016/j.molimm.2023.07.013
[29]	Jonsson AH, Zhang F, Dunlap G, et al. Granzyme K⁺ CD8 T cells form a core population in inflamed human tissue[J]. Sci Transl Med, 2022, 14(649): eabo0686. doi：10.1126/scitranslmed.abo0686
[30]	Durham LE, Humby FC, Ng N, et al. Substantive similarities between synovial fluid and synovial tissue T cells in inflammatory arthritis via single-cell RNA and T cell receptor sequencing[J]. Arthritis Rheumatol, 2024, 76(11): 1594-601. doi：10.1002/art.42949

豨莶丸治疗类风湿关节炎的分子机制：基于蛋白质组学

Molecular mechanism of Xixian Pills for improving rheumatoid arthritis in rats: a proteomic analysis

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