银杏双黄酮通过抑制软骨细胞肿瘤坏死因子α改善膝骨关节炎表型的研究  

Ginkgetin attenuates the osteoarthritis progression by inhibiting the tumor necrosis factorαfrom chondrocytes

作　　者：王芸 周颖[2] 杨岚[3] WANG Yun;ZHOU Ying;YANG Lan(Dept.of Chinese Traditional Medicine,Wuhan Fourth Hospital,Wuhan 430022,Hubei,China;Dept.of Medicare,Zhongnan Hospital of Wuhan University,Wuhan 430071,Hubei,China;Dept.of Medical Affaire,Zhongnan Hospital of Wuhan University,Wuhan 430071,Hubei,China)

机构地区：[1]武汉市第四医院中医科,湖北武汉430022 [2]武汉大学中南医院医保部,湖北武汉430071 [3]武汉大学中南医院医务处,湖北武汉430071

出　　处：《武汉大学学报(医学版)》2025年第3期302-306,356,共6页Medical Journal of Wuhan University

摘　　要：目的:探索银杏双黄酮是否具有抗骨关节炎(OA)功效并探讨其机制。方法:利用前交叉韧带切断建立大鼠膝关节骨关节炎模型,关节腔注射银杏双黄酮,观察大鼠膝关节软骨退变表型;利用重组白细胞介素1β(IL-1β)构建体外退变软骨模型,予以50μmol·L^(-1)银杏双黄酮处理,检测软骨退变指标。结果:在体研究发现,银杏双黄酮关节腔注射可显著改善大鼠膝关节OA表型,降低关节软骨肿瘤坏死因子α(TNF-α)蛋白表达水平及关节液TNF-α浓度;体外研究发现,银杏双黄酮可显著降低IL-1β诱导的原代软骨细胞TNF-αmRNA及蛋白表达水平,并降低培养基TNF-α浓度;另外,银杏双黄酮可上调软骨细胞2型胶原(Col2a1)、蛋白多糖(Acan)mRNA水平,抑制基质金属蛋白酶13(MMP-13)、聚蛋白多糖酶5(Adamts-5)mRNA水平,并通过上调凋亡抑制基因B淋巴细胞瘤-2基因(Bcl-2)mRNA表达水平、抑制凋亡诱导基因硫胱胺酸蛋白酶3(Caspase 3)mRNA水平起到抗凋亡的作用。结论:银杏双黄酮可能通过抑制软骨细胞TNF-α、促进软骨基质合成、抑制软骨基质降解及软骨细胞凋亡,进而起到抗OA的作用。Objective:To study the possible effect and mechanism of Ginkgetin in osteoarthritis(OA)treat-ment.Methods:Rat knee OA models were developed by cutting the anterior cruciate ligament,and then the degeneration of the cartilage was observed after 4 times of intra-articular Ginkgetin(50μL of 100μg·mL^(-1))injection in the knee.Also,chondrocytes were treated with 50μmol·L^(-1) Ginkgetin af-ter induced by 10 ng·mL^(-1) IL-1βfor 24 h in vitro,and the degenerative features of the chondrocytes was detected.Results:Intra-articular Ginkgetin injection could partially rescue the cartilage from de-generation during OA progression in vivo,by down-regulating the protein expression of tumor necrosis factorα(TNF-α)in the cartilage and the level of TNF-αin the synovial fluid.Also,Ginkgetin attenuated the stimulated gene expression of TNF-αby interleukin 1βin the primary chondrocyte in vitro,as well as down-regulating the concentration of TNF-αin the culture supernatant.Further,we found that Ginkgetin also up-regulated the stimulated gene expression of collagen type 2a1(Col2a1),aggrecan(Acan)and B-cell lymphoma 2(Bcl-2),and down-regulated the gene expression of matrix metalloproteinase 13(MMP-13),Adamts-5(a disintegrin and metalloproteinase with thrombospondin motif 5),and Caspase 3.Conclusion:Ginkgetin might be a potential anti-OA agent,which promotes the biosynthesis and inhibits the degeneration of cartilage matrix,and inhibits the apoptosis of chondrocyte during OA progression.

关 键 词：骨关节炎 银杏双黄酮 肿瘤坏死因子Α 软骨细胞 

分 类 号：R961.1[医药卫生—药理学]