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南京中医药大学附属医院(江苏省中医院)骨伤科,南京 210029
硕士研究生。研究方向:膝骨关节炎发病机制及中药干预机制。E-mail:2091009510@qq.com
主任中医师,教授,博士生导师,博士。研究方向:中医骨伤科学的临床与基础。E-mail:fsyy00606@njucm.edu.cn
收稿:2026-04-23,
修回:2026-06-17,
录用:2026-07-10,
网络首发:2026-07-24,
纸质出版:2026-07-30
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宋佳宸,吴鹏,张立,等.膝痹宁Ⅱ方经JAK2/STAT3通路缓解KOA大鼠滑膜炎症及纤维化的机制研究 [J].中国药房,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.
宋佳宸,吴鹏,张立,等.膝痹宁Ⅱ方经JAK2/STAT3通路缓解KOA大鼠滑膜炎症及纤维化的机制研究 [J].中国药房,2026,37(14):1838-1844. DOI: 10.6039/j.issn.1001-0408.2026.14.07.
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.
目的
2
基于Janus激酶2(JAK2)/信号转导及转录激活因子3(STAT3)通路,探讨膝痹宁Ⅱ方缓解膝骨关节炎(KOA)大鼠滑膜炎症及纤维化的作用机制。
方法
2
将75只雄性SD大鼠随机分为假手术组(Sham组)、KOA组、膝痹宁Ⅱ低剂量组(XBNⅡ-L组,4 g/kg)、高剂量组(XBNⅡ-H组,8 g/kg)、膝痹宁Ⅱ高剂量联合STAT3激活剂Colivelin三氟乙酸盐(C-TFA)组[C-TFA组,8 g/kg膝痹宁Ⅱ+1.0 mg/(kg·d) C-TFA],每组15只。除Sham组外,其余各组采用前交叉韧带离断法建立KOA模型。造模成功后,各药物组分别给予相应药物灌胃和(或)腹腔注射,每日1次,持续28 d。末次给药后,评估各组大鼠膝关节滑膜组织病理改变并进行指标计算;检测血清炎症因子水平,检测膝关节滑膜组织中磷酸化JAK2(p-JAK2)、磷酸化STAT3(p-STAT3)蛋白阳性表达,滑膜组织JAK2/STAT3通路相关蛋白及mRNA表达。
结果
2
与Sham组相比,KOA组大鼠滑膜衬里细胞显著增生且排列紊乱,Krenn评分,纤维化占比,p-JAK2、p-STAT3阳性面积百分比,p-JAK2/JAK2、p-STAT3/STAT3和Ⅰ型胶原蛋白、
α
-平滑肌肌动蛋白的表达水平,JAK2、STAT3、Ⅰ型胶原蛋白、
α
-平滑肌肌动蛋白mRNA的表达水平,以及血清白细胞介素1β、白细胞介素18水平均显著升高(
P
<0.05)。与KOA组相比,XBNⅡ-L组、XBNⅡ-H组大鼠上述病理改变明显改善,各指标均显著下降(
P
<0.05),且XBNⅡ-H组的改善效果显著优于XBNⅡ-L组(
P
<0.05)。与XBNⅡ-H组相比,C-TFA组上述病理损伤加重,各指标均显著恶化(
P
<0.05)。
结论
2
膝痹宁Ⅱ方可减轻KOA大鼠滑膜炎症与纤维化,其机制可能与抑制JAK2/STAT3通路激活有关。
OBJECTIVE
2
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.
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 .
冯晓晴 , 蔡道章 , 余星磊 , 等 . 基于GBD大数据中国膝骨关节炎疾病负担现状与趋势分析 [J ] . 现代预防医学 , 2022 , 49 ( 10 ): 1753 - 1760 .
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 .
施蕾 , 刘德仁 , 刘江宇 , 等 . 膝痹宁Ⅱ方抑制TGF-β/Smad3介导巨噬细胞-肌成纤维细胞的转化改善KOA滑膜纤维化 [J ] . 南京中医药大学学报 , 2026 , 42 ( 3 ): 388 - 397 .
吴孝政 , 黄高 , 王力子 , 等 . 玉屏风散对博来霉素诱导的肺纤维化大鼠中JAK2/STAT3信号通路的干预机制研究 [J ] . 时珍国医国药 , 2025 , 36 ( 15 ): 2861 - 2870 .
康俊峰 , 揭立士 , 伏厚宇 , 等 . 膝痹宁Ⅱ联合脂肪干细胞外泌体调控线粒体自噬改善膝骨关节炎的机制 [J ] . 中国实验方剂学杂志 , 2024 , 30 ( 11 ): 111 - 119 .
胡恩睿 , 魏义保 , 刘德仁 , 等 . 膝痹宁Ⅱ方调控SETDB2/H3K9me3信号轴缓解寒湿痹阻型KOA大鼠冷刺激疼痛敏感性的机制 [J ] . 中国药房 , 2026 , 37 ( 3 ): 324 - 330 .
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 .
曹子丰 , 梅伟 , 张立 , 等 . 膝痹宁Ⅱ方内服治疗寒湿痹阻型膝骨关节炎临床疗效的回顾性队列研究 [J ] . 中国实验方剂学杂志 , 2024 , 30 ( 14 ): 122 - 129 .
魏义保 , 马振源 , 廖太阳 , 等 . “易层”贴敷对膝骨关节炎大鼠滑膜纤维化的改善作用及机制 [J ] . 中国药房 , 2024 , 35 ( 4 ): 407 - 412 .
刘建华 , 赵海勇 , 温芳 , 等 . 炎性细胞因子在膝骨关节炎中的表达及与高敏C反应蛋白和红细胞沉降率的相关性 [J ] . 天津医药 , 2020 , 48 ( 1 ): 55 - 58 .
朱宇喆 , 王其澜 , 梁琦兴 , 等 . 基于JAK2/STAT3通路探讨独活寄生汤治疗膝骨关节炎的作用机制 [J ] . 浙江中医杂志 , 2025 , 60 ( 12 ): 1112 - 1116 .
李宏军 , 钱亮 , 邓新超 , 等 . 舒筋活血胶囊通过JAK2/STAT3通路缓解大鼠膝骨关节炎的机制研究 [J ] . 天津医药 , 2023 , 51 ( 9 ): 961 - 967 .
向文远 , 邓迎杰 , 热米拉·艾买提 , 等 . 基于JAK2/STAT3信号通路探讨补肾痹通方抑制ECM降解及炎症反应对骨关节炎大鼠软骨保护的作用 [J ] . 新疆医科大学学报 , 2026 , 49 ( 2 ): 145 - 152 .
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 .
姜敬敏 . 桑根皮活性成分桑辛素通过下调STAT3表达减轻力竭运动诱导的肾损伤 [J ] . 分子植物育种 , 2025 , 23 ( 21 ): 7278 - 7285 .
杨丽娜 , 孔慧 , 贾平 . 藏红花酸通过下调STAT3活性抑制糖尿病视网膜病变 [J ] . 眼科新进展 , 2025 , 45 ( 7 ): 526 - 532 .
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 .
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