苗药“四大血”通过抑制HIF-1α/PDK1介导的糖酵解重编程调控巨噬细胞极化并缓解胶原诱导型关节炎大鼠滑膜炎症

doi:10.12122/j.issn.1673-4254.2026.09.08

南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (9): 2078-2090.doi: 10.12122/j.issn.1673-4254.2026.09.08

• • 上一篇

苗药“四大血”通过抑制HIF-1α/PDK1介导的糖酵解重编程调控巨噬细胞极化并缓解胶原诱导型关节炎大鼠滑膜炎症

沈婉婷¹(), 陈一哲¹(), 付欣予¹, 袁家涛¹, 周均¹, 黄丽²(), 吴宁²()

^1.贵州医科大学，临床医学院，贵州贵阳 561113
^2.贵州医科大学，基础医学实验教学中心，贵州贵阳 561113

收稿日期:2026-01-09 出版日期:2026-09-20 发布日期:2026-09-30
通讯作者: 黄丽,吴宁 E-mail:1527214678@qq.com;2322045095@qq.com;12155501@qq.com;1638210715@qq.com
作者简介:沈婉婷，在读本科生，E-mail: 1527214678@qq.com
陈一哲，在读本科生，E-mail: 2322045095@qq.com
第一联系人：（沈婉婷、陈一哲并列第一作者）
基金资助:
国家自然科学基金(82260829);2024年国家级大学生创新创业计划训练项目(2024106600520)

Miao medicine Sidaxue regulates macrophage polarization and alleviates synovial inflammation in collagen-induced arthritis rats by inhibiting HIF-1α/PDK1-mediated glycolytic reprogramming

Wanting SHEN¹(), Yizhe CHEN¹(), Xinyu FU¹, Jiatao YUAN¹, Jun ZHOU¹, Li HUANG²(), Ning WU²()

^1.Clinical Medical College, Guizhou Medical University, Guiyang 561113, China
^2.Basic Medical Experimental Teaching Center, Guizhou Medical University, Guiyang 561113, China

Received:2026-01-09 Online:2026-09-20 Published:2026-09-30
Contact: Li HUANG, Ning WU E-mail:1527214678@qq.com;2322045095@qq.com;12155501@qq.com;1638210715@qq.com
Supported by:
National Natural Science Foundation of China(82260829)

摘要/Abstract

摘要：

目的探究贵州苗医验方“四大血”（SX）对胶原诱导型关节炎（CIA）大鼠滑膜组织糖酵解和巨噬细胞极化的作用机制。方法将32只SD大鼠随机均分为空白组、模型组、雷公藤多苷片阳性对照组（GTW 40 mg/kg）、SX组（SX 40 g/kg），8只/组。除空白组外，其余组别均构建CIA大鼠模型。造模成功后，灌胃给药21 d，其中空白组与模型组灌胃生理盐水。检测大鼠足肿度、关节炎指数（AI），HE染色观察滑膜组织病理变化，免疫荧光染色检测滑膜组织诱导型一氧化氮合酶（iNOS）、甘露糖受体（CD206）表达，ELISA法检测血清肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）水平，分光光度法检测滑膜组织乳酸含量，Western blotting与实时荧光定量PCR法检测缺氧诱导因子-1α（HIF-1α）、丙酮酸脱氢酶激酶同工酶1（PDK1）、己糖激酶2（HK2）的蛋白及mRNA表达。采用UHPLC-MS鉴定SX入血成分并预测靶点，通过差异分析和WGCNA鉴定类风湿关节炎（RA）相关基因，经Venn交集分析锁定候选靶点，再通过多种机器学习算法筛选关键枢纽基因。利用AlphaFold3预测HIF-1α与PDK1的互作结构，对关键基因进行虚拟敲除，使用分子对接探究靶点与入血成分的互作关系。结果动物实验中，与模型组相比，SX能显著减轻CIA大鼠关节肿胀度和AI评分（P<0.01）；改善滑膜增生与炎性细胞浸润；降低血清 TNF-α、IL-1β、IL-6 含量（P<0.05）；下调iNOS表达、上调CD206 表达，抑制巨噬细胞M1型极化；同时显著下调滑膜组织中HIF-1α、PDK1、HK2的蛋白及mRNA表达水平（P<0.01）；鉴定出29种SX入血活性成分、756个潜在靶点及908个RA核心相关基因，经交集分析获得38个候选靶点，机器学习筛选出9个关键基因。AlphaFold3 预测显示HIF-1α与PDK1存在强互作关系，虚拟敲除分析表明，敲除HIF1A和PDK1可显著扰动巨噬细胞中TNF、NF-κB等炎症信号通路，分子对接显示互作较强。结论本研究通过全方动物实验和入血成分预测分析验证了苗药“四大血”可通过抑制HIF-1α/PDK1信号通路，纠正糖酵解重编程，进而促进巨噬细胞M2型极化，有效缓解CIA大鼠关节炎症。

关键词: 类风湿关节炎, 四大血, HIF-1α/PDK1通路, 糖酵解重编程, 巨噬细胞极化

Abstract:

Objective To investigate the mechanism of Miao medicine prescription Sidaxue (SX) for inhibiting glycolysis in the synovial tissue and promoting macrophage polarization in rats with collagen-induced arthritis (CIA). Methods Thirty-two SD rats were randomized into normal control group, CIA model group, tripterygium glycosides (40 mg/kg; positive control) treatment group, and SX (40 g/kg) treatment group (n=8). Except for those in the normal control group, all the rats were subjected to CIA modeling and treated with saline, tripterygium glycosides or SX by gavage for 21 consecutive days. Paw swelling, arthritis index, synovial pathology, inflammatory factors, glycolysis-related indicators and gene expressions were detected. UHPLC-MS was used to screen the components of SX in the blood of SX-treated rats. The target genes of the active components of SX and rheumatoid arthritis (RA) were predicted using bioinformatics analysis, and the hub genes were identified using machine learning algorithms. The binding sites between HIF-1α and PDK1 were predicted using AlphaFold3, and the interactions between SX components and their targets were simulated using molecular docking. Results SX treatment significantly alleviated joint swelling, lowered arthritis scores, improved synovial lesions, and reduced serum levels of TNF-α, IL-1β and IL-6 in CIA rats, resulting in also inhibition of macrophage polarization and down-regulation of HIF-1α, PDK1 and HK2 expressions in the synovial tissues. Twenty-nine components of SX were detected in the blood of SX-treated rats, and 9 key target genes were identified. AlphaFold3 predicted a strong interaction between HIF-1α and PDK1, and their virtual knockout was shown to disturb the inflammatory pathways in the macrophages. Molecular docking studies suggested stable docking between the active components of SX and their key targets. Conclusion SX alleviates joint inflammation in CIA rats by inhibiting the HIF-1α/PDK1 signaling pathway, correcting glycolytic reprogramming, and promoting M2 polarization of macrophages.

Key words: rheumatoid arthritis, Sidaxue, HIF-1α/PDK1 pathway, glycolytic reprogramming, macrophage polarization

沈婉婷, 陈一哲, 付欣予, 袁家涛, 周均, 黄丽, 吴宁. 苗药“四大血”通过抑制HIF-1α/PDK1介导的糖酵解重编程调控巨噬细胞极化并缓解胶原诱导型关节炎大鼠滑膜炎症[J]. 南方医科大学学报, 2026, 46(9): 2078-2090.

Wanting SHEN, Yizhe CHEN, Xinyu FU, Jiatao YUAN, Jun ZHOU, Li HUANG, Ning WU. Miao medicine Sidaxue regulates macrophage polarization and alleviates synovial inflammation in collagen-induced arthritis rats by inhibiting HIF-1α/PDK1-mediated glycolytic reprogramming[J]. Journal of Southern Medical University, 2026, 46(9): 2078-2090.

图/表 12

参考文献 40

[1]	Di Matteo A, Bathon JM, Emery P. Rheumatoid arthritis[J]. Lancet, 2023, 402(10416): 2019-33. doi：10.1016/s0140-6736(23)01525-8
[2]	Parab A, Bhatt LK. T-cell metabolism in rheumatoid arthritis: focus on mitochondrial and lysosomal dysfunction[J]. Immunopharmacol Immunotoxicol, 2024, 46(3): 378-84. doi：10.1080/08923973.2024.2330645
[3]	Xu J, Feng ZT, Chen SX, et al. Taxol alleviates collagen-induced arthritis in mice by inhibiting the formation of microvessels[J]. Clin Rheumatol, 2019, 38(1): 19-27. doi：10.1007/s10067-017-3646-1
[4]	Touhidul Islam SM, Won J, Khan M, et al. Hypoxia-inducible factor-1 drives divergent immunomodulatory functions in the pathogenesis of autoimmune diseases[J]. Immunology, 2021, 164(1): 31-42. doi：10.1111/imm.13335
[5]	Damerau A, Kirchner M, Pfeiffenberger M, et al. Metabolic reprogramming of synovial fibroblasts in osteoarthritis by inhibition of pathologically overexpressed pyruvate dehydrogenase kinases[J]. Metab Eng, 2022, 72: 116-32. doi：10.1016/j.ymben.2022.03.006
[6]	Škorja Milić N, Dolinar K, Miš K, et al. Suppression of pyruvate dehydrogenase kinase by dichloroacetate in cancer and skeletal muscle cells is isoform specific and partially independent of HIF-1α[J]. Int J Mol Sci, 2021, 22(16): 8610. doi：10.3390/ijms22168610
[7]	雷海桃, 王金海, 高韵奇, 等. 己糖激酶2在类风湿关节炎发病机制中的研究进展[J]. 中国骨质疏松杂志, 2025, 31(1): 90-5.
[8]	Chen JX, Li GR, Sun DJ, et al. Research progress of hexokinase 2 in inflammatory-related diseases and its inhibitors[J]. Eur J Med Chem, 2024, 264: 115986. doi：10.1016/j.ejmech.2023.115986
[9]	Su PF, Li O, Ke K, et al. Targeting tumor-associated macrophages: Critical players in tumor progression and therapeutic strategies (Review)[J]. Int J Oncol, 2024, 64(6). doi：10.3892/ijo.2024.5648
[10]	Cersosimo F, Lonardi S, Bernardini G, et al. Tumor-associated macrophages in osteosarcoma: from mechanisms to therapy[J]. Int J Mol Sci, 2020, 21(15): 5207. doi：10.3390/ijms21155207
[11]	Peng Y, Zhou MX, Yang H, et al. Regulatory mechanism of M1/M2 macrophage polarization in the development of autoimmune diseases[J]. Mediat Inflamm, 2023, 2023: 8821610. doi：10.1155/2023/8821610
[12]	Kzhyshkowska J, Shen JX, Larionova I. Targeting of TAMs: can we be more clever than cancer cells?[J]. Cell Mol Immunol, 2024, 21(12): 1376-409. doi：10.1038/s41423-024-01232-z
[13]	Siouti E, Andreakos E. The many facets of macrophages in rheumatoid arthritis[J]. Biochem Pharmacol, 2019, 165: 152-69. doi：10.1016/j.bcp.2019.03.029
[14]	余芸, 蔡伟伟, 周静, 等. 代谢重编程调控巨噬细胞极化及其在类风湿关节炎中的作用[J]. 药学学报, 2020, 55(9): 2027-34. doi：10.16438/j.0513-4870.2020-0386
[15]	Kumar V. Inflammation research sails through the sea of im-munology to reach immunometabolism[J]. Int Immunopharmacol, 2019, 73: 128-45. doi：10.1016/j.intimp.2019.05.002
[16]	欧慧萍, 吴趋荟, 沈枭, 等. 中医药防治类风湿关节炎的作用机制研究进展[J]. 吉林中医药, 2021, 41(12): 1685-8.
[17]	袁桃花, 黄宇键, 李佳豪, 等. 贵州苗药方“四大血”对CIA大鼠滑膜血管增生的作用机制[J]. 西安交通大学学报: 医学版, 2019, 40(5): 824-9, 843. doi：10.7652/jdyxb201905031
[18]	吴宁, 曾佳, 王时敏, 等. 苗药四大血对大鼠佐剂性关节炎作用的研究[J]. 中国实验方剂学杂志, 2014, 20(2): 120-3. doi：10.11653/syfj2014020120
[19]	梁玺, 覃淇, 张艺馨, 等. 苗药验方“四大血”对类风湿性关节炎大鼠关节炎症的作用及机制[J]. 贵州医科大学学报, 2023, 48(7): 759-66.
[20]	吴宁, 袁桃花, 姬进忠, 等. 苗药验方四大血对人类风湿性关节炎成纤维样滑膜细胞凋亡和焦亡的影响[J]. 南方医科大学学报, 2021, 41(10): 1473-83. doi：10.12122/j.issn.1673-4254.2021.10.05
[21]	Wu N, Yuan TH, Yin ZX, et al. Network pharmacology and molecular docking study of the Chinese Miao medicine sidaxue in the treatment of rheumatoid arthritis[J]. Drug Des Devel Ther, 2022, 16: 435-66. doi：10.2147/dddt.s330947
[22]	马麦丽娜, 李喜媛, 马晓飞, 等. 中医药调控M1/M2巨噬细胞极化治疗类风湿关节炎研究进展[J]. 中国医药导刊, 2025, 27(8): 780-5.
[23]	胡白飞, 高倩茹, 胡海明, 等. 中药物质基础研究进展：从化学物质组学到肠道转化物质组学[J]. 中国生物工程杂志, 2026, 46(4): 142-54.
[24]	陈旺宇, 节笑笑, 陈甜甜, 等. 中药血清药物化学研究现状[J]. 中国医药科学, 2023, 13(4): 26-9, 86.
[25]	彭鹏, 李佳欣, 杨新月, 等. 基于UPLC-Q-Exactive Orbitrap MS分析泻白散在正常和慢性支气管炎小鼠体内的入血成分及其代谢差异[J]. 中国实验方剂学杂志, 2026, 32(1): 219-27.
[26]	郭帅, 褚小磊, 沈桐, 等. 两种佐剂制备CIA大鼠模型的效果比较[J]. 蚌埠医学院学报, 2022, 47(3): 281-4.
[27]	王琎, 尹葳, 蔡雪阳, 等. 基于SOCS1/STAT3信号通路探究红禾麻乙酸乙酯部位对Ⅱ型胶原诱导关节炎大鼠的影响[J]. 中成药, 2023, 45(7): 2364-7.
[28]	王远迎, 戴兴月, 陈春彦, 等. 苗药验方四大血可减少关节炎大鼠滑膜组织的坏死性凋亡和血管新生: 基于抑制RIPK1/RIPK3/MLKL通路[J]. 南方医科大学学报, 2022, 42(12): 1774-82. doi：10.12122/j.issn.1673-4254.2022.12.04
[29]	Li XJ, Li FX, Jing WY, et al. Effect of heat-reinforcing needling on hypoxia-inducible factor 1α and glycolysis activity in rabbits with cold syndrome of rheumatoid arthritis[J]. Acupunct Res, 2024, 49(6): 585-93. doi：10.13702/j.1000-0607.20230487
[30]	Wu TZ, Hu EQ, Xu SB, et al. clusterProfiler 4.0: a universal enrichment tool for interpreting omics data[J]. Innovation, 2021, 2(3): 100141. doi：10.1016/j.xinn.2021.100141
[31]	Gu ZG, Eils R, Schlesner M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data[J]. Bioinformatics, 2016, 32(18): 2847-9. doi：10.1093/bioinformatics/btw313
[32]	Osorio D, Zhong Y, Li GX, et al. scTenifoldKnk: an efficient virtual knockout tool for gene function predictions via single-cell gene regulatory network perturbation[J]. Patterns, 2022, 3(3): 100434. doi：10.1016/j.patter.2022.100434
[33]	Wang Q, Ren JH, Lin X, et al. Inflammatory stimulus-responsive polymersomes reprogramming glucose metabolism mitigates rheumatoid arthritis[J]. Biomaterials, 2025, 312: 122760. doi：10.1016/j.biomaterials.2024.122760
[34]	尹煜辉, 李琰, 齐保玉, 等. 基于有氧糖酵解探究补骨生髓方含药血清通过介导HIF-1α促进MC3T3-E1细胞成骨分化的作用[J].湖南中医药大学学报, 2025, 45(5): 818-24.
[35]	Jin ZX, Kho J, Dawson B, et al. Nitric oxide modulates bone anabolism through regulation of osteoblast glycolysis and differentiation[J]. J Clin Invest, 2021, 131(5): e138935. doi：10.1172/jci138935
[36]	Pei XY, Lu LJ, Huang ZQ, et al. Activation of M1 macrophages promotes diabetic kidney disease by modulating glycolysis via HIF-1α‑HK2 signaling pathway[J]. Diabetol Metab Syndr, 2025, 17(1): 362. doi：10.1186/s13098-025-01894-3
[37]	Tardito S, Martinelli G, Soldano S, et al. Macrophage M1/M2 polarization and rheumatoid arthritis: a systematic review[J]. Autoimmun Rev, 2019, 18(11): 102397. doi：10.1016/j.autrev.2019.102397
[38]	Ye L, Wen ZY, Li YQ, et al. Interleukin-10 attenuation of collagen-induced arthritis is associated with suppression of interleukin-17 and retinoid-related orphan receptor γt production in macrophages and repression of classically activated macrophages[J]. Arthritis Res Ther, 2014, 16(2): R96. doi：10.1186/ar4544
[39]	Muraille E, Leo O, Moser M. TH1/TH2 paradigm extended: macrophage polarization as an unappreciated pathogen-driven escape mechanism[J]? Front Immunol, 2014, 5: 603. doi：10.3389/fimmu.2014.00603
[40]	李淼, 李瑞, 杨晓芳, 等. 橙皮苷调控mTOR/HIF-1α通路对高糖诱导的肾小球系膜细胞自噬的影响[J]. 天津中医药, 2025, 42(1): 78-83.

Primer	Sequences (5' to 3')
HK2	Forward Reverse	GCTGCTGCTGAAGAAGATGG
HK2	Forward Reverse	CCAGAGGGAGTCGATGTTGA
HIF-1α	Forward Reverse	GCTGATTTGTGAGCCTTCTATG
HIF-1α	Forward Reverse	TCATCTGTAAGTGGGTCTCGT
PDK1	Forward Reverse	ATGGCGTCCGTGGAGAAGTA
PDK1	Forward Reverse	TCAGTCTTGGCGTAGTCGTT
GAPDH	Forward Reverse	GAAGCTGGTCATCAACGGGA
GAPDH	Forward Reverse	GGCGGAGATGATGACCCTTT

Primer	Sequences (5' to 3')
HK2	Forward Reverse	GCTGCTGCTGAAGAAGATGG
HK2	Forward Reverse	CCAGAGGGAGTCGATGTTGA
HIF-1α	Forward Reverse	GCTGATTTGTGAGCCTTCTATG
HIF-1α	Forward Reverse	TCATCTGTAAGTGGGTCTCGT
PDK1	Forward Reverse	ATGGCGTCCGTGGAGAAGTA
PDK1	Forward Reverse	TCAGTCTTGGCGTAGTCGTT
GAPDH	Forward Reverse	GAAGCTGGTCATCAACGGGA
GAPDH	Forward Reverse	GGCGGAGATGATGACCCTTT

Group	TNF-α	IL-1β	IL-6
Normal	30.81±4.56	12.14±1.85	32.79±4.26
Model	62.86±5.68**	54.52±4.51**	79.78±5.35**
GTW	39.82±5.88^#	32.36±3.97^#	42.65±6.31^#
SX	32.62±6.43^##	30.89±2.36^##	33.52±4.54^##

Group	TNF-α	IL-1β	IL-6
Normal	30.81±4.56	12.14±1.85	32.79±4.26
Model	62.86±5.68**	54.52±4.51**	79.78±5.35**
GTW	39.82±5.88^#	32.36±3.97^#	42.65±6.31^#
SX	32.62±6.43^##	30.89±2.36^##	33.52±4.54^##

Serial number	t (min)	Component	Lon species	Measured value (m/z)	Score
1	3.32	Fumaritine	[M+H]⁺	356.15	0.99
2	3.46	Heriguard	[M+H C₇H₁₂O₆]⁺	163.04	0.99
3	3.55	Procyanidin B2	[M+H]⁺	579.15	0.99
4	3.63	Magnoflorine	[M]⁺	342.17	0.93
5	4.26	3-O-Feruloylquinic acid	[M+H]⁺	369.12	0.99
6	4.31	Glu-Thr	[M+H]⁺	249.11	0.93
7	5.16	N-Malonyltryptophan	[M+H]⁺	291.10	0.83
8	5.43	7-hydroxy-4-(methoxymethyl)coumarin	[M+H]⁺	207.06	0.89
9	5.51	Brutieridin	[M+H C₁₈H₂₈O₁₃]⁺	303.09	0.92
10	5.90	4-Hydroxy-7-methyl-2-[2-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] oxypropan-2-yl]-2,3-dihydrofuro[3,2-g]chromen-5-one	[M+H]⁺	439.16	0.97
11	7.15	Toddalolactone	[M+H]⁺	309.13	1.00
12	7.89	Visamminol	[M+H]⁺	277.11	0.96
13	8.48	Skimmianine	[M+H]⁺	260.09	0.95
14	9.34	Isopimpinellin	[M+H]⁺	247.06	1.00
15	10.01	Pimpinellin	[M+H]+	247.06	1.00
16	12.12	Phellopterin	[M+H]⁺	301.11	0.98
17	2.84	Neochlorogenic acid	[M-H]^-	353.09	0.97
18	3.36	Wikstrol A	[M-H C₆H₆O₃]-	417.10	0.73
19	3.95	Catechin	[M-H]^-	289.07	1.00
20	4.09	2-beta-D-Glucopyranosyloxy-4-methoxy-cis-cinnamic acid	[M-H-H₂O]^-	337.09	0.98
21	4.37	(-)-Lyoniresinol 9'-O-glucoside	[M-H]^-	581.22	0.95
22	4.79	N-Acetyl-L-phenylalanine	[M-H]^-	206.08	0.98
23	5.15	Asn-Asn	[M-H]^-	245.09	0.73
24	5.51	Hesperidin	[M-H]^-	609.18	1.00
25	6.32	Azelaic acid	[M-H]^-	187.10	1.00
26	6.60	Salicylic acid	[M-H]^-	137.02	1.00
27	8.35	1-O-[(2beta,3beta,5xi,9xi,18xi)-2,23-Dihydroxy-28,29-dioxo-3- (beta-D-xylopyranosyloxy)olean-12-en-28-yl]-beta-D-glucopyranose	[M-H]^-	825.43	0.99
28	10.76	Mocimycin	[M-H]^-	795.42	0.97
29	11.22	Medicagenic acid 3-O-beta-D-glucoside	[M-H]^-	663.37	0.97

苗药“四大血”通过抑制HIF-1α/PDK1介导的糖酵解重编程调控巨噬细胞极化并缓解胶原诱导型关节炎大鼠滑膜炎症

Miao medicine Sidaxue regulates macrophage polarization and alleviates synovial inflammation in collagen-induced arthritis rats by inhibiting HIF-1α/PDK1-mediated glycolytic reprogramming

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

图/表 12

参考文献 40

相关文章 15

编辑推荐

Metrics

本文评价

Blood-entering component	Vina score for HIF1A(kcal/mol)
(-)-Lyoniresinol 9'-O-glucoside	-7.70
2-beta-D-Glucopyranosyloxy-4-methoxy-cis-cinnamic acid	-6.70
1-O-[(2beta,3beta,5xi,9xi,18xi)-2,23-Dihydroxy-28,29-dioxo-3-(beta-D-xylopyranosyloxy)olean-12-en-28-yl]-beta-D-glucopyranose	-9.00
3-O-Feruloylquinic acid	-7.70
2-(4-Hydroxy-7-methyl-5-oxo-2,3-dihydro-5H-furo[3,2-g]chromen-2-yl)propan-2-yl hexopyranoside	-8.70
Wikstrol A	-8.60
7-hydroxy-4-(methoxymethyl)coumarin	-6.00
Asn-Asn	-6.30
Azelaic acid	-5.30
Brutieridin	-8.70
Catechin	-7.50
Fumaritine	-7.80
Glu-Thr	-5.80
Heriguard	-7.80
Hesperidin	-9.30
Isopimpinellin	-6.60
Magnoflorine	-8.10
Medicagenic acid 3-O-beta-D-glucoside	-10.10
Mocimycin	-8.90
N-Acetyl-L-phenylalanine	-6.40
Neochlorogenic acid	-7.70
N-Malonyltryptophan	-7.30
Phellopterin	-7.30
Pimpinellin	-6.70
Procyanidin B2	-8.50
Salicylic acid	-6.30
Skimmianine	-6.60
Toddalolactone	-6.70
Visamminol	-7.30

[1]	王伟丽, 高怡琳, 洪馨, 陈义珍, 程梦, 张磊, 戴荣, 王亿平. 清肾颗粒通过调控Akt3介导的M1型巨噬细胞极化改善单侧输尿管梗阻小鼠肾纤维化[J]. 南方医科大学学报, 2026, 46(6): 1216-1227.
[2]	杨云恒, 贾雅清, 尹高生, 李双秀, 杨萍. 乳酸通过“心-胃轴”促进巨噬细胞 M1 型极化诱导胃黏膜损伤[J]. 南方医科大学学报, 2026, 46(6): 1267-1277.
[3]	陈义珍, 王伟丽, 程梦, 张威, 高怡琳, 洪馨, 张磊, 戴荣, 王亿平. 清肾颗粒通过调控糖酵解重编程及组蛋白 H3K18 乳酸化减轻小鼠肾纤维化[J]. 南方医科大学学报, 2026, 46(3): 582-591.
[4]	孙梦雨, 汪元, 刘菲菲. 黄芩清热除痹胶囊调控LncRNA EBLN3P/miR-369-3p/NFIX轴抑制JAK/STAT通路介导的类风湿关节炎滑膜血管新生[J]. 南方医科大学学报, 2026, 46(3): 675-685.
[5]	李楠, 张亮, 郭俏凤, 周越, 刘长江. 有氧运动通过调控miR-221-3p介导的脂肪组织巨噬细胞极化改善小鼠胰岛素抵抗[J]. 南方医科大学学报, 2026, 46(1): 74-82.
[6]	张兆君, 吴琼, 谢苗苗, 叶洳吟, 耿晨晨, 石纪雯, 杨清玲, 王文锐, 石玉荣. 层状双氢氧化物负载si-NEAT1通过miR-133b/PD-L1轴调控乳腺癌紫杉醇耐药及巨噬细胞极化[J]. 南方医科大学学报, 2025, 45(8): 1718-1731.
[7]	李玮怡, 江露, 张宗星, 陈丹, 包卓玛, 黄丽, 袁林. 强骨康疏方通过抑制HIF-1α/BNIP3自噬信号通路减少类风湿性关节炎大鼠的破骨细胞分化[J]. 南方医科大学学报, 2025, 45(7): 1389-1396.
[8]	涂舒谕, 陈祥宇, 李程辉, 黄丹萍, 张莉. 补阳还五汤通过调控外泌体miR-590-5p介导的巨噬细胞极化延缓大鼠血管衰老[J]. 南方医科大学学报, 2025, 45(6): 1251-1259.
[9]	牛民主, 殷丽霞, 乔通, 尹林, 张可妮, 胡建国, 宋传旺, 耿志军, 李静. 旱莲苷A通过调控JAK2/STAT3通路抑制M1型巨噬细胞极化改善葡聚糖硫酸钠诱导的小鼠结肠炎[J]. 南方医科大学学报, 2025, 45(6): 1297-1306.
[10]	俞佳雯, 周薏, 钱春美, 穆蓝, 阙任烨. 铁过载诱导的小鼠肝纤维化过程影响巨噬细胞M2极化[J]. 南方医科大学学报, 2025, 45(4): 684-691.
[11]	高志, 吴傲, 胡仲翔, 孙培养. 类风湿性关节炎中氧化应激与免疫浸润的生物信息学分析[J]. 南方医科大学学报, 2025, 45(4): 862-870.
[12]	曹周芳, 汪元, 王梦娜, 孙玥, 刘菲菲. LINC00837/miR-671-5p/SERPINE2功能轴促进类风湿关节炎成纤维细胞样滑膜细胞的恶性病理学过程[J]. 南方医科大学学报, 2025, 45(2): 371-378.
[13]	张芡, 刘博文, 雷丽, 王晔, 张馨月, 毛樟坤, 唐鹏, 张金梅, 杨佳宜, 彭彦茜, 刘泽. 丝氨酸蛋白酶抑制剂E1过表达通过诱导M2型巨噬细胞极化促进三阴性乳腺癌细胞增殖与紫杉醇耐药[J]. 南方医科大学学报, 2025, 45(12): 2551-2560.
[14]	刘新新, 徐迎芮, 盛红娜, 刘昊. 人源脐带间充质干细胞移植通过Chi3l1抑制M1型巨噬细胞极化减轻1型糖尿病小鼠的炎症反应[J]. 南方医科大学学报, 2025, 45(12): 2738-2746.
[15]	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.