摘要
目的探讨槲皮素(quercetin,Quer)对NF-κB活性的影响及对类风湿关节炎大鼠软骨细胞基质降解和细胞凋亡的作用。方法建立Ⅱ型胶原诱导性关节炎(collagen-induced arthritis,CIA)大鼠模型,设立CIA模型组、Quer治疗组并以正常大鼠作为对照组,比较各组大鼠AI指数和足趾容积;ELISA检测关节腔液中IL-1β、MMP-13含量;Western blot检测关节软骨组织中p-p65、MMP-13蛋白的表达。体外培养大鼠软骨组织细胞,分为control组、IL-1β处理组,检测软骨组织培养液中MMP-13、Hyp和蛋白多糖含量。将体外培养的软骨细胞分为3组:control组、IL-1β组、IL-1β+Quer组,检测软骨细胞内p-p65、MMP-13、COL2A1蛋白表达,流式检测细胞凋亡。结果与control组相比,CIA组大鼠AI指数和足趾容积明显增加,关节腔液中IL-1β、MMP-13含量以及软骨组织中p-p65、MMP-13蛋白表达明显增加;给予Quer治疗可显著降低大鼠的AI指数和足趾容积,使软骨组织内p-p65、MMP-13蛋白表达量明显减少,关节腔液中IL-1β、MMP-13含量明显降低。IL-1β处理可明显升高软骨组织培养基中MMP-13、Hyp含量,使蛋白多糖含量明显减少。IL-1β处理明显上调软骨细胞内p-p65、MMP-13蛋白表达,使COL2A1蛋白表达明显减少,软骨细胞凋亡明显增加;给予Quer处理则明显抑制软骨细胞内p-p65、MMP-13蛋白表达,使COL2A1表达量增加,细胞凋亡明显减少。结论 Quer可通过抑制NF-κB激活,减弱炎症环境下软骨细胞内MMP-13产生、基质降解和细胞凋亡,起到保护软骨的作用。
This study was performed to investigate the effects of quercetin on the activity of NF-kappa B and the downregulation of chondrocytes matrix degradation and apoptosis in rats with rheumatoid arthritis. Collageninduced arthritis(CIA) model was established in rat, and CIA model group and Quer treatment group were set up,while normal rats were used as control group. The AI index and toe volume of all rat were measured and compared;the levels of IL-1β and MMP-13 in articular cavity fluid were detected by ELISA;Western blot was used to detect the protein expression of p-p65 and MMP-13 in articular cartilage tissue. Rat chondrocytes were culture in vitro and divided into control group and IL-1β treatment group. The contents of MMP-13, Hyp and proteoglycan in cartilage tissue culture medium were detected. Furthermore, the chondrocytes cultured in vitro were divided into 3 groups:control group, IL-1β group, and IL-1β+Quer group, for comparing the protein expressions of p-p65, MMP-13 and COL2 A1, as well as the apoptosis in chondrocytes. Data showed that compared with control group, CIA group demontraed significantly hgher AI index, toe volume, higher levels of IL-1β and MMP-13 in articular cavity, and higher protein expressions of p-p65 and MMP-13 in cartilage tissue. Quer treatment could effectively reduce the AI index and toe volume, the protein expressions of p-p65 and MMP-13 in cartilage tissue, and the contents of IL-1β and MMP-13 in articular cavity fluid of CIA rats. IL-1β treatment increased the levels of MMP-13 and Hyp,while decreased the content of proteoglycan in cartilage tissue culture medium after. Also, IL-1β treatment increased the protein expressions of p-p65 and MMP-13, then downregulated the expression of COL2 A1 and apoptosis in chondrocytes. Quercetin treatment could inhibit the protein expressions of p-p65 and MMP-13,upregulate the expression of COL2 A1, and downregulate the apoptosis of chondrocytes. So we made a conclution that quercetin can protect cartilage by inhibiting NF-kappa B activ
作者
王友庆
陈士芳
梅珏
WANG Youqing;CHENG Shifang;MEI Jue(Department of Rheumatology, Huzhou Central Hospital, Huzhou 313000, China)
出处
《免疫学杂志》
CAS
CSCD
北大核心
2019年第6期485-491,共7页
Immunological Journal
