[1]赵俊淞,贾琼△,罗虎,等.活血利水方干预膝骨关节炎大鼠的疗效及对NF-κB/HIF-1α/VEGF信号通路的调控作用[J].中国中医骨伤科杂志,2026,34(04):22-29.[doi:10.20085/j.cnki.issn1005-0205.260404]
　ZHAO Junsong,JIA Qiong,LUO Hu,et al.The Therapeutic Effect of Huoxue Lishui Formula on Knee Osteoarthritis in Rats and Its Regulatory Role in the NF-κB/HIF-1α/VEGF Signaling Pathway[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2026,34(04):22-29.[doi:10.20085/j.cnki.issn1005-0205.260404]
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活血利水方干预膝骨关节炎大鼠的疗效及对NF-κB/HIF-1α/VEGF信号通路的调控作用()

《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第34卷
期数:
2026年04期
页码:
22-29
栏目:
基础研究
出版日期:
2026-04-10

文章信息/Info

Title:
The Therapeutic Effect of Huoxue Lishui Formula on Knee Osteoarthritis in Rats and Its Regulatory Role in the NF-κB/HIF-1α/VEGF Signaling Pathway
文章编号:
1005-0205(2026)04-0022-08
作者:
赵俊淞1; 贾琼1△; 罗虎1; 何宇1; 罗凌威1; 曹雨林1; 张作夫1
1湖南中医药大学附属省直中医医院(湖南 株洲,412000)
Author(s):
ZHAO Junsong1; JIA Qiong1△; LUO Hu1; HE Yu1; LUO Lingwei1; CAO Yulin1; ZHANG Zuofu1
1Hunan Province Directly Affliated TCM Hospital,Zhuzhou 412000,Hunan China.
关键词:
活血利水方;  膝骨关节炎;  血管内皮生长因子;  缺氧诱导因子1α;  核转录因子κB;  动物实验;  信号通路调控
Keywords:
Huoxue Lishui formula;  knee osteoarthritis(KOA);  vascular endothelial growth factor(VEGF);  hypoxia-inducible factor-1α(HIF-1α);  nuclear factor κB(NF-κB);  animal experiments;  signaling pathway regulation
分类号:
R285.5
DOI:
10.20085/j.cnki.issn1005-0205.260404
文献标志码:
A
摘要:
目的:探讨活血利水方通过调控NF-κB/HIF-1α/VEGF信号通路对膝骨关节炎(KOA)的治疗作用及其机制。方法:将36只SD大鼠分为中药组、西药组、模型组和假手术组,每组9只。采用Hulth手术诱导模型组、中药组和西药组大鼠右后肢建立膝骨关节炎大鼠模型,假手术组大鼠仅切开右侧膝关节内侧皮肤及皮下组织,暴露关节腔后缝合。造模成功后,中药组大鼠按照生药量6 g/(kg?d)以活血利水方药物灌胃,西药组按照12 mg/(kg?d)给予塞来昔布溶液灌胃,模型组和假手术组按照10 mL/(kg?d)以生理盐水灌胃。连续干预8周后,取各组大鼠血液、膝关节软骨及滑膜组织,通过HE染色观察病理变化,ELISA法检测血清TNF-α、HIF-1α和血管内皮生长因子(VEGF)水平,Western Blot法和qRT-PCR分别检测NF-κB/HIF-1α/VEGF通路相关蛋白及mRNA表达。结果:模型组血清TNF-α、HIF-1α和VEGF水平显著高于假手术组,差异有统计学意义(均P<0.001); 中药组TNF-α、HIF-1α和VEGF水平及西药组VEGF水平均显著低于模型组,差异有统计学意义(P=0.001,P<0.001,P<0.001,P<0.001),而西药组TNF-α和HIF-1α水平与模型组差异无统计学意义(P=0.435,0.905)。中药组VEGF含量低于西药组,差异有统计学意义(P<0.001)。模型组NF-κB、HIF-1α和VEGF的mRNA表达显著高于假手术组,差异有统计学意义(P=0.002,P=0.003,P<0.001); 中药组NF-κB、HIF-1α和VEGF及西药组NF-κB和HIF-1α的mRNA表达显著低于模型组,差异有统计学意义(P<0.05),而西药组VEGF mRNA表达与模型组差异无统计学意义(P=0.511)。与西药组相比,中药组NF-κB和HIF-1α的mRNA表达显著下调,差异有统计学意义(P=0.023,0.045)。模型组滑膜组织中NF-κB、HIF-1α和VEGF蛋白表达显著高于假手术组,差异有统计学意义(P<0.001,P=0.029,P<0.001); 中药组NF-κB、HIF-1α和VEGF及西药组NF-κB和VEGF蛋白表达显著低于模型组,差异有统计学意义(P<0.05),而西药组HIF-1α蛋白表达与模型组差异无统计学意义(P=0.533)。与西药组相比,中药组NF-κB和VEGF蛋白表达显著下调,差异有统计学意义(P<0.001)。HE染色显示,模型组软骨破坏及炎性细胞浸润较假手术组明显加重; 中药组和西药组病理改变较模型组减轻,且中药组改善程度优于西药组。结论:活血利水方可能通过抑制NF-κB/HIF-1α/VEGF信号通路的活化,减轻滑膜炎性反应、膝关节炎症,减少新生血管形成,从而延缓膝骨关节炎进展。
Abstract:
Objective:This study aims to investigate the therapeutic effects and underlying mechanisms of the Huoxue Lishui formula in treating knee osteoarthritis(KOA)through regulation of the NF-κB/HIF-1α/VEGF signaling pathway.Methods:Thirty-six SD rats were divided into Chinese medicine group,Western medicine group,model group,and sham-operated group,with 9 rats in each group.KOA models were established in the right hind limbs of rats in the model group,the Chinese medicine group,and the Western medicine group using the Hulth surgery procedure.For the sham-operated group,only the medial skin and subcutaneous tissue of the right knee joint were incised to expose the joint cavity,which was then sutured.After successful modeling,rats in the Chinese medicine group were administered the Huoxue Lishui formula via oral gavage at a crude drug dose of 6 g/(kg?d),the Western medicine group received celecoxib solution at 12 mg/(kg?d)via oral gavage,and the model group and sham-operated group were given normal saline at 10 mL/(kg?d)via oral gavage.The intervention lasted for 8 weeks.Blood,knee joint cartilage,and synovial tissues were collected from each group.Pathological changes were observed using HE staining,serum levels of TNF-α,HIF-1α,and VEGF were detected by ELISA,and the protein and mRNA expression levels of NF-κB/HIF-1α/VEGF pathway-related factors were measured by Western Blot and qRT-PCR,respectively.Results:Compared with the sham-operated group,the model group exhibited significantly increased serum levels of TNF-α,HIF-1α,and VEGF(all P<0.001).Huoxue Lishui formula treatment significantly reduced the levels of all three factors(TNF-α,P=0.001; HIF-1α,P<0.001; VEGF,P<0.001),while the Western medicine group showed a significant reduction only in VEGF(P<0.001),with no significant effects on TNF-α(P=0.435)or HIF-1α(P=0.905).The VEGF content in the Chinese medicine group was lower than that in the Western medicine group,with statistical significance(P<0.001).At the molecular level,mRNA expression of NF-κB,HIF-1α,and VEGF was significantly upregulated in the model group(all P<0.01).Huoxue Lishui formula downregulated the mRNA expression of all three genes(all P<0.001),outperforming the Western medicine group in suppressing NF-κB(P=0.023)and HIF-1α(P=0.045)mRNA expression.The Western medicine group had no significant effect on VEGF mRNA(P=0.511).In the model group,the protein levels of synovial NF-κB,HIF-1α,and VEGF were higher than those in the sham-operated group(P<0.001,P=0.029,P<0.001).Treatment with Chinese medicine significantly reduced all three proteins,whereas Western medicine reduced NF-κB/VEGF(P<0.05).Chinese medicine resulted in lower levels of NF-κB/VEGF compared with Western medicine(P<0.001).Histopathological results confirmed that Huoxue Lishui formula provided the most significant improvement in cartilage structure and exhibited the strongest anti-inflammatory effect.Conclusion:Huoxue Lishui formula may delay the progression of KOA by suppressing the activation of the NF-κB/HIF-1α/VEGF signaling pathway,thereby reducing synovial inflammation,knee joint inflammatory responses,and pathological neovascularization.

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(收稿日期:2025-08-29)

备注/Memo

备注/Memo:
基金项目:湖南省教育厅优秀青年项目(24B1112)
湖南省中医药科研项目(A2024043)
湖南省“十四五”第二批中医药领军人才项目
△通信作者 E-mail:04170731@163.com
更新日期/Last Update: 2026-04-15