[1]胡恩睿,魏义保,廖太阳,等.基于PPARγ/c-Ski信号通路探讨蔓荆子黄素对膝骨关节炎大鼠滑膜组织纤维化的影响及其作用机制[J].中医正骨,2025,37(04):11-19,29.
　HU Enrui,WEI Yibao,LIAO Taiyang,et al.Exploring the effects and mechanism of casticin on synovial fibrosis in knee osteoarthritis rats based on the PPARγ/c-Ski signaling pathway[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2025,37(04):11-19,29.
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基于PPARγ/c-Ski信号通路探讨蔓荆子黄素对膝骨关节炎大鼠滑膜组织纤维化的影响及其作用机制()
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《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第37卷
期数:
2025年04期
页码:
11-19,29
栏目:
基础研究
出版日期:
2025-04-20

文章信息/Info

Title:
Exploring the effects and mechanism of casticin on synovial fibrosis in knee osteoarthritis rats based on the PPARγ/c-Ski signaling pathway
作者:
胡恩睿; 魏义保; 廖太阳; 刘德仁; 龚子健; 王培民
南京中医药大学附属医院,江苏 南京 210029
Author(s):
HU Enrui; WEI Yibao; LIAO Taiyang; LIU Deren; GONG Zijian; WANG Peimin
Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,Jiangsu,China
关键词:
骨关节炎; 膝;  滑膜;  纤维化;  蔓荆子;  黄酮醇类;  炎症;  过氧化物酶体增生物激活受体;  c-Ski;  信号传导;  大鼠
Keywords:
osteoarthritis; knee;  synovial membrane;  fibrosis;  viticis fructus;  flavonols;  lnflammation;  peroxisome proliferator-activated receptors;  c-Ski;  signal transduction;  rats
摘要:
目的:探讨蔓荆子黄素对膝骨关节炎(knee osteoarthritis,KOA)大鼠滑膜组织纤维化的影响及其作用机制。方法:将 40只成年雄性SD大鼠随机分为假手术组、模型组、低浓度组、高浓度组和拮抗剂组,每组8只。模型组、低浓度组、高浓度组和拮抗剂组大鼠均采用前交叉韧带离断法建立右侧KOA模型。造模14 d后,低浓度组和高浓度组大鼠分别按照0.2 mg·kg-1·d-1和0.4 mg·kg-1·d-1的剂量给予蔓荆子黄素灌胃; 拮抗剂组大鼠在给予蔓荆子黄素灌胃的同时,每日按照1.0 mg·kg-1的剂量腹腔注射GW9662溶液; 假手术组、模型组、低浓度组、高浓度组大鼠均每日腹腔注射等体积生理盐水; 连续干预14 d。干预结束后,采用ELISA试剂盒检测大鼠血清白细胞介素(interleukin,IL)-1β、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)含量; 采用HE染色试剂盒、Masson染色试剂盒分别对大鼠膝关节滑膜组织进行染色,观察大鼠滑膜炎症程度与纤维化程度; 分别采用实时定量PCR和Western Blot法检测大鼠膝关节滑膜组织中转化生长因子(transforming growth factor,TGF)-β、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、Ⅰ型胶原、过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR)γ、c-Ski的mRNA和蛋白表达水平。结果:①血清IL-1β和TNF-α含量检测结果。模型组大鼠血清IL-1β、TNF-α含量均高于假手术组(P=0.000,P=0.000),低浓度组和高浓度组大鼠血清IL-1β、TNF-α含量均低于模型组(IL-1β:P=0.004,P=0.000; TNF-α:P=0.000,P=0.000),拮抗剂组大鼠血清IL-1β、TNF-α含量均高于高浓度组(P=0.027,P=0.005)。②膝关节滑膜组织病理学观察结果。模型组大鼠膝关节滑膜组织部分缺损,衬里层细胞排列不规则,滑膜细胞大量增生,炎症细胞浸润明显,胶原纤维大量沉积; 与模型组相比,低浓度组、高浓度组大鼠膝关节滑膜组织衬里层细胞排列较为规则,炎症细胞浸润明显减轻,胶原纤维沉积减轻; 与高浓度组相比,拮抗剂组大鼠膝关节滑膜组织炎症细胞浸润更严重,胶原纤维沉积更多。③滑膜组织纤维化相关基因的mRNA和蛋白表达量检测结果。模型组大鼠滑膜组织中TGF-β、α-SMA、Ⅰ型胶原的mRNA和蛋白相对表达量均高于假手术组(P=0.000,P=0.000,P=0.000; P=0.000,P=0.000,P=0.000),低浓度组和高浓度组大鼠滑膜组织中TGF-β、α-SMA、Ⅰ型胶原的mRNA和蛋白相对表达量均低于模型组(mRNA:P=0.000,P=0.000,P=0.000; P=0.000,P=0.000,P=0.000; 蛋白:P=0.000,P=0.000,P=0.000; P=0.000,P=0.000,P=0.000),高浓度组大鼠滑膜组织中TGF-β、α-SMA、Ⅰ型胶原的mRNA和蛋白相对表达量均低于低浓度组(P=0.000,P=0.021,P=0.001; P=0.001,P=0.000,P=0.002),拮抗剂组大鼠滑膜组织中TGF-β、α-SMA、Ⅰ型胶原的mRNA和蛋白相对表达量均高于高浓度组(P=0.000,P=0.001,P=0.001; P=0.002,P=0.001,P=0.020)。④滑膜组织中PPARγ/c-Ski信号通路相关基因的mRNA和蛋白表达量检测结果。模型组大鼠滑膜组织中PPARγ、c-Ski的mRNA和蛋白相对表达量均低于假手术组(P=0.000,P=0.000; P=0.000,P=0.000),低浓度组和高浓度组大鼠滑膜组织中PPARγ、c-Ski的mRNA和蛋白相对表达量均高于模型组(mRNA:P=0.001,P=0.000; P=0.004,P=0.000; 蛋白:P=0.001,P=0.000; P=0.004,P=0.000),高浓度组大鼠滑膜组织中PPARγ、c-Ski的mRNA和蛋白相对表达量均高于低浓度组(mRNA:P=0.000,P=0.000; 蛋白:P=0.049,P=0.000),拮抗剂组大鼠滑膜组织中PPARγ、c-Ski的mRNA和蛋白相对表达量均低于高浓度组(mRNA:P=0.000,P=0.000; 蛋白:P=0.000,P=0.000)。结论:蔓荆子黄素能够改善KOA大鼠滑膜组织纤维化,且高浓度蔓荆子黄素比低浓度蔓荆子黄素的改善效果更佳; 其作用机制可能与其能够激活PPARγ/c-Ski信号通路、抑制炎症反应有关。
Abstract:
Objective:To observe the effects of casticin(CAS)on synovial fibrosis in knee osteoarthritis(KOA)rats,and to explore its underlying mechanism.Methods:Forty adult male SD rats were randomized into sham-operated group,model group,low-concentration group,high-concentration group,and antagonist group,with 8 ones in each group.All rats but the ones in sham-operated group were modeled by anterior cruciate ligment transection(ACLT)on the right knees for inducing KOA.Fourteen days after successful modeling,the rats in low- and high-concentration groups were intervened by intragastric administration with CAS at doses of 0.2 and 0.4 mg/kg/day,respectively; the ones in antagonist group firstly by intragastric administration with CAS,followed by intraperitoneal injection of GW9662 solution at a dose of 1.0 mg/kg; while the ones in sham-operated group,model group,low-concentration group,and high-concentration group by intraperitoneal injection of the same dose of normal saline every day for consecutive 14 days.After the end of intervention,the serum levels of interleukin(IL)-1β and tumor necrosis factor-α(TNF-α)were detected using ELISA kit.After that,the rat knee synovial tissues were harvested and stained with HE staining kit,and Masson staining kit,respectively,to observe the degree of synovial inflammation and fibrosis.Furthermore,the mRNA and protein expression levels of transforming growth factor(TGF)-β,α-smooth muscle actin(α-SMA),type I collagen,peroxisome proliferator-activated receptor(PPAR)γ,and c-Ski in the knee synovial tissues were detected by real-time quantitative PCR(RT-qPCR)and Western Blot,respectively.Results:①The serum levels of IL-1β and TNF-α.The serum levels of IL-1β and TNF-α were higher in model group compared to sham-operated group(P=0.000,P=0.000),were lower in low- and high-concentration groups compared to model group(IL-1β:P=0.004,P=0.000; TNF-α:P=0.000,P=0.000),and were higher in antagonist group compared to high-concentration group(P=0.027,P=0.005).②The pathological changes in knee synovial tissues.The changes,manifesting as partially defective knee synovial tissues,irregularly arranged lining layer cells,significantly proliferated synovial cells,substantially deposited collagen fibers,and obvious inflammatory cells infiltration,were observed in rats of model group.Compared with that of model group,the knee synovial tissues of rats in low- and high-concentration groups exhibited as more uniformly arranged lining layer cells,marked reduced inflammatory cell infiltration,and decreased collagen fiber deposition.While,compared with that of high-concentration group,the rats in antagonist group presented as more severe inflammatory cell infiltration and more increased collagen fiber deposition.③The mRNA and protein expression levels of fibrosis-related genes in the knee synovial tissues.The relative mRNA and protein expression levels of TGF-β,α-SMA,and type I collagen in knee the synovial tissues were higher in model group compared to sham-operated group(P=0.000,P=0.000,P=0.000; P=0.000,P=0.000,P=0.000),were lower in low- and high-concentration groups compared to model group(mRNA:P=0.000,P=0.000,P=0.000; P=0.000,P=0.000,P=0.000; protein:P=0.000,P=0.000,P=0.000; P=0.000,P=0.000,P=0.000),were lower in high-concentration group compared to low-concentration group(P=0.000,P=0.021,P=0.001; P=0.001,P=0.000,P=0.002),and were higher in antagonist group compared to high-concentration group(P=0.000,P=0.001,P=0.001; P=0.002,P=0.001,P=0.020).④The mRNA and protein expression levels of PPARγ/c-Ski signaling pathway-related genes in the knee synovial tissues.The relative mRNA and protein expression levels of PPARγ and c-Ski in the knee synovial tissues were lower in model group compared to sham-operated group(P=0.000,P=0.000; P=0.000,P=0.000),were higher in low- and high-concentration groups compared to model group(mRNA:P=0.001,P=0.000; P=0.004,P=0.000; protein:P=0.001,P=0.000; P=0.004,P=0.000),were higher in high-concentration group compared to low-concentration group(mRNA:P=0.000,P=0.000; protein:P=0.049,P=0.000),and were lower in an-tagonist group compared to high-concentration group(mRNA:P=0.000,P=0.000; protein:P=0.000,P=0.000).Conclusion:CAS can ameliorate the fibrosis of synovial tissues in KOA rats,and the high-concentration CAS behaves better compared to the low-concentration one.It may work by activating the PPARγ/c-Ski signaling pathway and inhibiting the inflammatory responses.

参考文献/References:

[1] PRIETO-ALHAMBRA D,JUDGE A,JAVAID M K,et al.Incidence and risk factors for clinically diagnosed knee,hip and hand osteoarthritis:influences of age,gender and osteoarthritis affecting other joints[J].Ann Rheum Dis,2014,73(9):1659-1664.
[2] HUNTER D J,BIERMA-ZEINSTRA S.Osteoarthritis[J].Lancet,2019,393(10182):1745-1759.
[3] LI Z,HUANG Z,BAI L.Cell interplay in osteoarthritis[J].Front Cell Dev Biol,2021,9:720925.
[4] MATHIESSEN A,CONAGHAN P G.Synovitis in osteoarthritis:current understanding with therapeutic implications[J].Arthritis Res Ther,2017,19(1):18.
[5] HERRERO-BEAUMONT G,LARGO R.Glucosamine and O-GlcNAcylation:a novel immunometabolic therapeutic target for OA and chronic,low-grade systemic inflammation?[J].Ann Rheum Dis,2020,79(10):1261-1263.
[6] MU Y,HAO W,LI S.Casticin protects against IL-1β-induced inflammation in human osteoarthritis chondrocytes[J].Eur J Pharmacol,2019,842:314-320.
[7] ZHOU L,DONG X,WANG L,et al.Casticin attenuates liver fibrosis and hepatic stellate cell activation by blocking TGF-β/Smad signaling pathway[J].Oncotarget,2017,8(34):56267-56280.
[8] LIU D,MEI W,KANG J,et al.Casticin ameliorates osteoarthritic cartilage damage in rats through PI3K/AKT/HIF-1α signaling[J].Chem Biol Interact,2024,391:110897.
[9] ZHANG L,LI M,LI X,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,2021,35:141-151.
[10] 廖太阳,马振源,康俊峰,等.基于“柔肝养筋”理论探讨小鼠肝脏来源外泌体对膝骨关节炎模型小鼠膝关节软骨的影响[J].中医正骨,2024,36(3):7-14.
[11] LI X,MEI W,HUANG Z,et al.Casticin suppresses monoiodoacetic acid-induced knee osteoarthritis through inhibiting HIF-1α/NLRP3 inflammasome signaling[J].Int Immunopharmacol,2020,86:106745.
[12] PRIMORAC D,MOLNAR V,ROD E,et al.Knee osteoarthritis:a review of pathogenesis and state-of-the-art non-operative therapeutic considerations[J].Genes(Basel),2020,11(8):854.
[13] 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.
[14] LONG H,LIU Q,YIN H,et al.Prevalence trends of site-specific osteoarthritis from 1990 to 2019:findings from the global burden of disease study 2019[J].Arthritis Rheumatol,2022,74(7):1172-1183.
[15] RIM Y A,JU J H.The role of fibrosis in osteoarthritis progression[J].Life(Basel),2021,11(1):3.
[16] LIU Q,HAN M,WU Z,et al.DDX5 inhibits hyaline cartilage fibrosis and degradation in osteoarthritis via alternative splicing and G-quadruplex unwinding[J].Nat Commun,2024,4(5):664-680.
[17] MENG X M,NIKOLIC-PATERSON D J,LAN H Y.TGF-β:the master regulator of fibrosis[J].Nat Rev Nephrol,2016,12(6):325-338.
[18] VAN DER KRAAN P M.The changing role of TGFβ in healthy,ageing and osteoarthritic joints[J].Nat Rev Rheumatol,2017,13(3):155-163.
[19] DAMERAU A,ROSENOW E,ALKHOURY D,et al.Fibro-tic pathways and fibroblast-like synoviocyte phenotypes in osteoarthritis[J].Front Immunol,2024,15:1385006.
[20] FRIEDMAN S L.Mechanisms of hepatic fibrogenesis[J].Gastroenterology,2008,134(6):1655-1669.
[21] CHANG X M,CHANG Y,JIA A.Effects of interferon-alpha on expression of hepatic stellate cell and transforming growth factor-beta1 and alpha-smooth muscle actin in rats with hepatic fibrosis[J].World J Gastroenterol,2005,11(17):2634-2636.
[22] DE LANGE-BROKAAR B J,IOAN-FACSINAY A,VAN OSCH G J,et al.Synovial inflammation,immune cells and their cytokines in osteoarthritis:a review[J].Osteoarthritis Cartilage,2012,20(12):1484-1499.
[23] SRIWATANANUKULKIT O,DESCLAUX S,TAWONSAWATRUK T,et al.Effectiveness of losartan on infrapatellar fat pad/synovial fibrosis and pain behavior in the monoiodoacetate-induced rat model of osteoarthritis pain[J].Biomed Pharmacother,2023,158:114121.
[24] REMST D F,BLANEY DAVIDSON E N,VAN DER KRAAN P M.Unravelling osteoarthritis-related synovial fibrosis:a step closer to solving joint stiffness[J].Rheumatology(Oxford),2015,54(11):1954-1963.
[25] REMST D F,BLANEY DAVIDSON E N,VITTERS E L,et al.Osteoarthritis-related fibrosis is associated with both elevated pyridinoline cross-link formation and lysyl hydroxylase 2b expression[J].Osteoarthritis Cartilage,2013,21(1):157-164.
[26] ZHANG L,XING R,HUANG Z,et al.Synovial fibrosis involvement in osteoarthritis[J].Front Med(Lausanne),2021,8:684389.
[27] CUNNINGTON R H,NAZARI M,DIXON I M.c-Ski,Smurf2,and Arkadia as regulators of TGF-β signaling:new targets for managing myofibroblast function and cardiac fibrosis[J].Can J Physiol Pharmacol,2009,87(10):764-772.
[28] 刘德仁,廖太阳,魏义保,等.基于PI3K/AKT/HIF-1α信号通路研究易层敷贴缓解TGF-β1诱导的膝骨关节炎大鼠滑膜纤维化的机制[J].南京中医药大学学报,2023,39(8):738-745.
[29] ABDELHADY R,CAVALU S,SABER S,et al.Mirtazapine,an atypical antidepressant,mitigates lung fibrosis by suppressing NLPR3 inflammasome and fibrosis-related mediators in endotracheal bleomycin rat model[J].Biomed Pharmacother,2023,161:114553.
[30] LUAN Z L,ZHANG C,MING W H,et al.Nuclear receptors in renal health and disease[J].EBioMedicine,2022,76:103855.
[31] MIRZA A Z,ALTHAGAFI I I,SHAMSHAD H.Role of PPAR receptor in different diseases and their ligands:physiological importance and clinical implications[J].Eur J Med Chem,2019,166:502-513.
[32] WANG J,GUO L,SHEN D,et al.The role of c-SKI in regulation of TGFβ-induced human cardiac fibroblast proliferation and ECM protein expression[J].J Cell Biochem,2017,118(7):1911-1920.
[33] 李工博,李军,曾益军,等.PPARγ对TGFβ/smad信号通路阻遏子c-Ski的上调作用[J].生理学报,2011,63(1):62-68.
[34] 康毅,罗伟生,黄红,等.荔枝核总黄酮对肝纤维化大鼠模型PPARγ/c-Ski表达的影响[J].世界科学技术-中医药现代化,2016,18(1):106-111.
[35] WANG F,FAN K,ZHAO Y,et al.Apigenin attenuates TGF-β1-stimulated cardiac fibroblast differentiation and extracellular matrix production by targeting miR-155-5p/c-Ski/Smad pathway[J].J Ethnopharmacol,2021,265:113195.
[36] BAUMANN A,BURGER K,BRANDT A,et al.GW9662,a peroxisome proliferator-activated receptor gamma antagonist,attenuates the development of non-alcoholic fatty liver disease[J].Metabolism,2022,133:155233.

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[14]梁朝,蔡静怡,闫立,等.针刀疗法改善膝骨关节炎早期疼痛症状的疗效评价[J].中医正骨,2015,27(09):9.
　LIANG Zhao,CAI Jingyi,YAN Li,et al.Evaluation of the curative effect of needle-knife therapy for relieving knee pain in patients with early knee osteoarthritis[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2015,27(04):9.
[15]王建武,党建军,李强,等.四联疗法治疗膝骨关节炎[J].中医正骨,2015,27(08):44.
[16]刘红娟,郭会利,郭树农.云克联合中药治疗膝骨关节炎的护理[J].中医正骨,2015,27(08):75.
[17]陈卫衡.探索建立系统的膝骨关节炎中医临床科研范式 和理论体系[J].中医正骨,2015,27(07):1.
[18]帅波,沈霖,杨艳萍,等.加味青娥丸治疗膝骨关节炎的作用机制研究[J].中医正骨,2015,27(07):15.
　SHUAI Bo,SHEN Lin,YANG Yanping,et al.Study on the mechanism of action of Jiawei Qing'e Wan(加味青娥丸)for the treatment of knee osteoarthritis[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2015,27(04):15.
[19]梅其杰,袁长深,段戡,等.壮药骨痹方烫熨联合运动疗法治疗膝骨关节炎的临床研究[J].中医正骨,2015,27(07):27.
　MEI Qijie,YUAN Changshen,DUAN Kan,et al.Clinical study of the curative effect of hot compressing and rubbing with packet of Gubi Fang(骨痹方)combined with exercise therapy in the treatment of knee osteoarthritis[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2015,27(04):27.
[20]王丹辉,张燕,刘丽娟,等.重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白 关节腔注射联合中药薰洗治疗膝骨关节炎的临床研究[J].中医正骨,2015,27(07):31.
　WANG Danhui,ZHANG Yan,LIU Lijuan,et al.Clinical study on intra-articular injection of TypeⅡrecombinant human tumor necrosis factor receptor-Fc fusion protein combined with Chinese herbal steaming and washing therapy for treatment of knee osteoarthritis[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2015,27(04):31.

备注/Memo

备注/Memo:
基金项目:国家自然科学基金(82274545); 江苏省医学重点学科和医学重点实验室建设项目(JSDW202252); 江苏省中医院临床医学创新中心发展项目(Y2023zx05)
通讯作者:王培民 E-mail:drwpm@163.com
更新日期/Last Update: 1900-01-01