SONG Jiachen,WU Peng,ZHANG Li,et al.Mechanism study of Xibining Ⅱ formula in alleviating synovial inflammation and fibrosis in KOA rats via JAK2/STAT3 pathway[J].ZHONGGUO YAOFANG,2026,37(14):1838-1844.
SONG Jiachen,WU Peng,ZHANG Li,et al.Mechanism study of Xibining Ⅱ formula in alleviating synovial inflammation and fibrosis in KOA rats via JAK2/STAT3 pathway[J].ZHONGGUO YAOFANG,2026,37(14):1838-1844.DOI: 10.6039/j.issn.1001-0408.2026.14.07.
Mechanism study of Xibining Ⅱ formula in alleviating synovial inflammation and fibrosis in KOA rats via JAK2/STAT3 pathway
To investigate the mechanism of Xibining Ⅱ formula in alleviating synovial inflammation and fibrosis in knee osteoarthritis (KOA) rats based on Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway.
METHODS
2
Seventy-five male SD rats were randomly divided into sham operation group (Sham group), KOA group, Xibining Ⅱ low-dose group (XBNⅡ-L group, 4 g/kg), Xibining Ⅱ high-dose group (XBNⅡ-H group, 8 g/kg), and Xibining Ⅱ high-dose combined with STAT3 activator Colivelin trifluoroacetate (C-TFA) group [C-TFA group, 8 g/kg Xibining Ⅱ+ 1.0 mg/(kg·d) C-TFA], with 15 rats in each group. Except for the Sham group, the KOA model was established by anterior cruciate ligament transection in the other groups. After successful modeling, each group was given corresponding drugs by intragastric administration and (or) intraperitoneal injection once daily for 28 consecutive days. After the last medication, the pathological changes of synovial tissue of knee joint in each group were evaluated and the indicators were calculated. The levels of serum inflammatory factors were detected. The positive expressions of phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) in synovial tissue of the knee joint were detected. The expressions of JAK2/STAT3 pathway-related proteins and mRNAs in synovial tissue were detected.
RESULTS
2
Compared with the Sham group, the synovial lining cells in the KOA group showed significant proliferation and disordered arrangement; the Krenn score, fibrosis ratio, positive area percentage of p-JAK2 and p-STAT3, p-JAK2/JAK2 and p-STAT3/STAT3, protein expression of Collagen-Ⅰ and
α
-smooth muscle actin, the mRNA expression of JAK2, STAT3, Collagen-Ⅰ and
α
-smooth muscle actin, as well as serum levels of interleukin-1β and interleukin-18 were significantly increased (
P
<0.05). Compared with the KOA group, the above pathological changes were significantly improved in each dose group of Xibining Ⅱ formula, and all indicators were significantly decreased (
P
<0.05), with the XBNⅡ-H group showing better effects than the XBNⅡ-L group (
P
<0.05). Compared with the XBNⅡ-H group, the above pathological damages were aggravated in the C-TFA group, and all indicators were significantly worsened (
P
<0.05).
CONCLUSIONS
2
Xibining Ⅱ formula can alleviate synovial inflammation and fibrosis in KOA rats, and its mechanism may be related to inhibiting the activation of JAK2/STAT3 pathway.
关键词
Keywords
references
GBD 2021 Rheumatoid Arthritis Collaborators . Global,regional,and national burden of rheumatoid arthritis,1990-2020,and projections to 2050:a systematic analysis of the global burden of disease study 2021 [J ] . Lancet Rheumatol , 2023 , 5 ( 10 ): e594 - e610 .
Brophy R H , Fillingham Y A . AAOS clinical practice guideline summary:management of osteoarthritis of the knee(nonarthroplasty),third edition [J ] . J Am Acad Orthop Surg , 2022 , 30 ( 9 ): e721 - e729 .
Sellam J , Berenbaum F . The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis [J ] . Nat Rev Rheumatol , 2010 , 6 ( 11 ): 625 - 635 .
Zhang L , Xing R L , Huang Z Q , et al . Synovial fibrosis involvement in osteoarthritis [J ] . Front Med , 2021 , 8 : 684389 .
Zhang L , Li M C , Li X C , et al . Characteristics of sensory innervation in synovium of rats within different knee osteoarthritis models and the correlation between synovial fibrosis and hyperalgesia [J ] . J Adv Res , 2022 , 35 : 141 - 151 .
Chiba T , Yamada M , Hashimoto Y , et al . Development of a femtomolar-acting humanin derivative named Colivelin by attaching activity-dependent neurotrophic factor to its N terminus:characterization of Colivelin-mediated neuroprotection against Alzheimer’s disease-relevant insults in vitro and in vivo [J ] . J Neurosci , 2005 , 25 ( 44 ): 10252 - 10261 .
Krenn V , Morawietz L , Burmester G R , et al . Synovitis score:discrimination between chronic low-grade and high-grade synovitis [J ] . Histopathology , 2006 , 49 ( 4 ): 358 - 364 .
Ivanovska A , Mancuso P , Burke A , et al . Identification of disease-stage therapeutic responses of mesenchymal stromal cells retrieved from murine osteoarthritic joints [J ] . Front Cell Dev Biol , 2025 , 13 : 1521437 .
Zhang L , Xing R L , Huang Z Q , et al . Inhibition of synovial macrophage pyroptosis alleviates synovitis and fibrosis in knee osteoarthritis [J ] . Mediators Inflamm , 2019 , 2019 : 2165918 .
Cota P , Helmi S A , Hsu C , et al . Cytokine directed chondroblast trans-differentiation:JAK inhibition facilitates direct reprogramming of fibroblasts to chondroblasts [J ] . Cells , 2020 , 9 ( 1 ): 191 .
Zou F Z , Zhang K M , Sun X D , et al . Inhibiting arachidonate-5-lipoxygenase expression ameliorates osteoarthritis progression by suppressing ferroptosis via the JAK2/STAT3 signaling pathway [J ] . Free Radic Biol Med , 2026 , 246 : 334 - 349 .
O’Shea J J , Schwartz D M , Villarino A V , et al . The JAK-STAT pathway:impact on human disease and therapeutic intervention [J ] . Annu Rev Med , 2015 , 66 : 311 - 328 .
Johnson D E , O’Keefe R A , Grandis J R . Targeting the IL-6/JAK/STAT3 signalling axis in cancer [J ] . Nat Rev Clin Oncol , 2018 , 15 ( 4 ): 234 - 248 .
Long-term efficacy of three intra-articular injections in the treatment of knee osteoarthritis: a network meta-analysis
Mechanism of Qingre antai decoction in improving pregnancy outcomes of threatened abortion rats with blood heat syndrome based on JAK2/STAT3 and PI3K/AKT dual signaling pathways
Mechanism of Xibining Ⅱ in alleviating cold stimulus pain sensitivity in rats with cold-damp obstruction-type KOA by regulating SETDB2/H3K9me3 signaling axis
解毒消瘀膏联合硫酸氨基葡萄糖钾胶囊治疗膝骨关节炎的临床观察
补肾活血中药对比塞来昔布治疗膝骨性关节炎疗效与安全性的Meta分析
Related Author
WU Xiaofei
CHEN Yueping
HAN Jie
CHEN Kaining
SU Hong
HUANG Yongyuan
HONG Zhitao
HUANG Yuwen
Related Institution
Graduate School of Guangxi University of Chinese Medicine
Dept. of Orthopedics, The Second Affiliated Hospital of Guangxi University of Chinese Medicine
Dept. of Orthopedics, The First Affiliated Hospital of Guangxi University of Chinese Medicine
Dept. of Educational Administration, Henan University of Chinese Medicine
Fifth Clinical Medical College, Henan University of Chinese Medicine