Objective To study the mechanism of taraxasterol in the treatment of knee osteoarthritis(KOA)in rats.Methods KOA rats model was prepared by injecting 0.2 mL of 4% papain solution +0.03 mmol/L cysteine into the joint cavity.The taraxasterol 2.5 mg/kg(low-dose group),5 mg/kg(medium-dose group),10mg/kg(high-dose group)and saline(model group)were administered by gavage,respectively.The sham operation group was prepared by injecting 0.2 mL of normal saline into the joint cavity and gavage with normal saline.4 weeks after administration,the serum levels of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β),IL-6,matrix metalloproteinase-1(MMP-1),MMP-3 and cysteine aspartic acid protease-1(Capase-1)in were determined by enzymelinked immunosorption.The expression levels of microRNA(miRNA)-140 and miRNA-146a in articular cartilage tissue were determined by -time PCR(RT-qPCR).The protein expression levels of inhibitor of NF-κB(IκB),inhibitor κB kinase β(IKKβ),nuclear factor-κB(NF-κB),transforming growth factor-βactivated kinase 1(TAK1),NOD-like receptors 3(NLRP3),apoptosis-associated speck-like protein containing CARD(ASC)in articular cartilage tissue were determined by Western blot.The pathological observation of articular cartilage was conducted.Results Compared with the sham operation group,the serum levels of TNF-α,IL-1β,IL-6,MMP-1,MMP-3,Capase-1 and the protein expression levels of IκB,IKKβ,NFκB,TAK1,NLRP3,ASC and Mankin score in articular cartilage tissue in high-dose,medium-dose,low-dose group and model group was significantly increased(P<0.05),the expression levels of miRNA-140 and miRNA-146a in articular cartilage were significantly decreased(P<0.05).Compared with the model group,the serum levels of TNF-α,IL-1β,IL-6,MMP-1,MMP-3,Capase-1 and the protein expression levels of IκB,IKKβ,NF-κB,TAK1,NLRP3,ASC and Mankin score in articular cartilage tissue in high-dose,medium-dose and low-dose group was significantly decreased(P<0.05),it decreased significantly with the increase of dose(P<0.05),the expression levels of miRNA-140 and miRNA146a in articular cartilage were significantly increasedd(P<0.05),it increased significantly with the increase of dose(P<0.05).Conclusion Taraxasterol has a protective effect on KOA rats,alleviate the pathological changes of articular cartilage tissue,and it was dose-dependent.The mechanism might be related to inflammation inhibition,up-regulation of miRNA expression and activation blocked of TAK1/NF-κB,NLRP3 signaling pathway.
谢子康,史铭钰 *,蒋阳,王斌,沈鹏飞,郑冲,杨晓峰. 蒲公英甾醇治疗大鼠膝关节骨关节炎的作用机制初步探索[J]. 实用骨科杂志, 2022, 28(5): 416-421.
Xie Zikang,Shi Mingyu *,Jiang Yang,Wang Bin,Shen Pengfei,Zheng Chong,Yang Xiaofeng. Preliminary Study on the Mechanism of Taraxasterol in the Treatment of Knee Osteoarthritis in Rats. sygkzz, 2022, 28(5): 416-421.
[1]Paultre K,Cade W,Hernandez D,et al.Therapeutic effects of turmeric or curcumin extract on pain and function for individuals with knee osteoarthritis:a systematic review[J].BMJ Open Sport Exerc Med,2021,7(1):e000935.
[2]杨超,闫庆梓,唐洁,等.蒲公英挥发油成分分析及其抗炎抗肿瘤活性研究[J].中华中医药杂志,2018,33(7):3106-3111.
[3]Chen J,Wu W,Zhang M,et al.Taraxasterol suppresses inflammation in IL-1β-induced rheumatoid arthritis fibroblast-like synoviocytes and rheumatoid arthritis progression in mice[J].Int Immunopharmacol,2019,70(5):274-283.
[4]万海山,代伟宏,黄泽晓,等.蒲公英甾醇对类风湿关节炎成纤维样滑膜细胞的增殖、迁移和凋亡及TLR4/NF-κB信号通路的影响[J].医学研究杂志,2020,49(11):126-131.
[5]何强,尹宏,代凤雷,等.早期膝骨性关节炎模型大鼠的建立与验证[J].中国组织工程研究,2019,23(27):4338-4343.
[6]潘炳,周颖芳,方芳,等.骨性关节炎的国内外研究现状及治疗进展[J].中国中医基础医学杂志,2021,27(5):861-865.
[7]Nambi G.Does low level laser therapy has effects on inflammatory biomarkers IL-1β,IL-6,TNF-α,and MMP-13 in osteoarthritis of rat models-a systemic review and meta-analysis[J].Laser Med Sci,2020,36(4):475-484.
[8]Sun G,Ba CL,Gao R,et al.Association of IL-6,IL-8,MMP-13 gene polymorphisms with knee osteoarthritis susceptibility in the Chinese Han population[J].Biosci Rep,2019,39(2):BSR20181346.
[9]黄媛霞,徐海斌,郭春.白细胞介素-1β、肿瘤坏死因子α及基质金属蛋白酶13在骨关节炎中的表达及相关性[J].广东医学,2017,38(15):2301-2304.
[10]潘朝旺,王伟,万进军,等.金荞麦提取物对膝骨关节炎兔关节软骨Caspase-1、3、9及MMP-1的影响[J].中国老年学杂志,2019,39(20):5066-5069.
[11]赵光辉,杨磊,马建兵,等.大骨节病与骨性关节炎膝关节软骨下骨差异表达miRNA及其调控网络分析[J].西安交通大学学报(医学版),2021,42(3):414-418.
[12]Oliviero A,Della Porta G,Peretti GM,et al.MicroRNA in osteoarthritis:physiopathology,diagnosis and therapeutic challenge[J].British medical bulletin,2019,130(1):137-147.
[13]Li C,Hu Q,Chen Z,et al.MicroRNA-140 suppresses human chondrocytes hypertrophy by targeting SMAD1 and controlling the bone morphogenetic protein pathway in osteoarthritis[J].Am J Med Sci,2018,355(5):477-487.
[14]Cha Y,He Y,Ouyang K,et al.MicroRNA-140-5p suppresses cell proliferation and invasion in gastric cancer by targeting WNT1 in the WNT/β-catenin signaling pathway[J].Oncol Lett,2018,16(5):6369-6376.
[15]Soyocak A,Kurt H,Ozgen M,et al.miRNA-146a,miRNA-155 and JNK expression levels in peripheral blood mononuclear cells according to grade of knee osteoarthritis[J].Gene,2017,627(10):207-211.
[16]邹磊,周圆家,饶峰,等.miRNA-140、MMP-3在OA关节滑液中的表达及相关性研究[J].安徽医科大学学报,2015,50(9):1289-1292.
[17]施利华,李恒,郭潘,等.miRNA-27a和miRNA-146a在骨性关节炎患者中的诊断意义[J].中华全科医学,2020,18(3):412-414;418.
[18]廖建钊,章晓云,张璇.骨关节炎发生发展中的分子信号通路[J].中国组织工程研究,2020,24(21):3394-3400.
[19]田明月,彭程云,丁小芬,等.NF-κB信号通路在骨性关节炎软骨损伤机制中的研究进展[J].现代中西医结合杂志,2021,30(10):1131-1137.
[20]吴培刚,杨学栋,曹振昊,等.新型蛋白酶体抑制剂膝关腔内注射对兔骨关节炎的治疗作用及其机制[J].山东医药,2020,60(12):46-49.
[21]陈伟达,石玮,杨继国,等.川续断总皂苷调节miR-19a对大鼠骨关节炎软骨细胞SOX9/NF-κB信号通路的影响[J].中国药师,2020,23(5):824-829.
[22]莫选荣,谢江文,吕国菊,等.TAK1基因沉默对TNF-a诱导的滑膜细胞IL-6、IL-8表达的影响[J].中国应用生理学杂志,2017,33(5):471-475.
[23]张琪琪,胡勇,周定,等.ADAMTS-4与TAK1在骨关节炎软骨组织中表达的相关性研究[J].安徽医科大学学报,2014,49(3):343-346.
[24]赵紫琴,徐瑾,王瑞琳,等.类风湿性关节炎滑膜组织中NLRP3炎性小体及下游因子IL-1β/IL-18的表达及意义[J].临床与实验病理学杂志,2019,35(5):534-538.
[25]孙银铁,郭开今,蔡红星.NOD2、NLRP3在石膏关节制动法建立兔膝骨性关节炎模型关节软骨中的表达[J].中国组织工程研究,2018,22(8):1211-1216.
[26]刘宜昕,魏蔚,王阳,等.TNF-α和CRT双信号对RA患者滑膜组织NLRP3炎症小体的活化作用[J].检验医学,2020,35(4):363-369.
[27]陆光辉,褚志华,曾守逵,等.类风湿性关节炎患者外周血Nod样受体蛋白3炎症小体和白细胞介素1β表达[J].贵州医科大学学报,2019,44(6):725-729.