柚皮苷降低基质金属蛋白酶-13和多配体蛋白聚糖-4浓度修复兔膝骨关节软骨损伤的作用  

Naringin Reduces MMP-13 and Syndecan-4 in Synovial Fluid to Repair Cartilage Injury of Rabbit Knee Osteoarthritis

作　　者：刘雨煊 刘向春[1] 亓建[1] 吕天成 赵久丽 陈婧 马小芳 邓斌 叶超[1] LIU Yuxuan;LIU Xiangchun;QI Jian;Lü Tiancheng;ZHAO Jiuli;CHEN Jing;MA Xiaofang;DENG Bin;YE Chao(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China;Beijing University of Chinese Medicine Third Affiliated Hospital)

机构地区：[1]北京中医药大学东直门医院,北京100700 [2]北京中医药大学第三附属医院

出　　处：《中国中医骨伤科杂志》2024年第10期1-5,12,共6页Chinese Journal of Traditional Medical Traumatology & Orthopedics

基　　金：国家自然科学基金青年科学基金项目(82104710);北京中医药大学东直门医院后备青年人才培养项目(DZMG-QNHB0002)。

摘　　要：目的:探讨柚皮苷降低关节液基质金属蛋白酶-13(MMP-13)、多配体蛋白聚糖-4(Syndecan-4)浓度修复兔膝关节软骨损伤的作用。方法:将16只大耳白兔随机分为假手术组、模型组、柚皮苷组、阳性对照组,每组4只。关节软骨损伤造模后,模型组给予去离子水灌胃,柚皮苷组给予柚皮苷灌胃,阳性对照组给予硫酸氨基葡萄糖灌胃。于第12周采用酶联免疫吸附测定(ELISA)法检测关节液MMP-13、Syndecan-4浓度水平,显微CT(Micro-CT)观察关节软骨损伤结构修复,免疫组化法检测关节软骨损伤处P-Smad2表达水平。结果:与假手术组相比,模型组关节液MMP-13、Syndecan-4浓度显著升高(P<0.05),可见明显关节软骨损伤缺损表现,软骨损伤处骨体积分数、骨小梁分离度、骨小梁厚度参数明显不佳(P<0.05)。与模型组相比,柚皮苷组与阳性对照组关节液MMP-13、Syndecan-4浓度显著下降(P<0.05)。与模型组相比,柚皮苷组关节面出现明显修复表现,柚皮苷组关节软骨损伤处骨体积分数、骨小梁分离度、骨小梁厚度参数明显好转(P<0.05)。与模型组相比,柚皮苷组P-Smad2表达水平明显上升。结论:骨碎补主要活性成分柚皮苷可降低关节液MMP-13、Syndecan-4的浓度水平,改善兔膝关节软骨损伤结构,提高关节软骨损伤的修复水平,其可能的机制与激活TGF-β/Smad信号通路的表达水平密切相关。药证相应,TGF-β/Smad信号通路受到抑制引起炎症水平增强所致的关节软骨损伤可能是膝骨关节炎肝肾亏虚的证候特点之一。Objective:To investigate the effect of naringin on the repair of knee cartilage injury by reducing the concentration of matrix metalloproteinase-13(MMP-13)and Syndecan-4 in synovial fluid.Methods:16 large-eared white rabbits were randomly divided into four groups:sham surgery group,model group,naringin group,and positive control group,with 4 rabbits in each group.After the establishment of the articular cartilage injury model,the model group was given deionized water for gastric lavage,the naringin group was given naringin for gastric lavage,and the positive control group was given glucosamine sulfate for gastric lavage.At the 12th week,the levels of MMP-13 and Syndecan-4 in the synovial fluid were detected using the enzyme-linked immunosorbent assay(ELISA)method,the repair of articular cartilage injury structure was observed by Micro-CT,and the expression level of P-Smad2 at the site of articular cartilage injury was detected by immunohistochemical method.Results:Compared with the sham surgery group,the concentrations of MMP-13 and Syndecan-4 in the synovial fluid in the model group were significantly increased(P<0.05),indicating obvious articular cartilage injury and defect,bone volume fraction,trabecular separation and trabecular thickness at the site of cartilage injury were significantly lower(P<0.05).Compared with model group,the concentrations of MMP-13 and Syndecan-4 in synovial fluid of naringin group and positive control group were significantly decreased(P<0.05).Compared with model group,naringin group showed obvious repair performance of articular surface,and naringin group significantly improved bone volume fraction,trabecular separation and trabecular thickness at articular cartilage injury(P<0.05).Compared with the model group,the expression level of P-Smad2 in naringin group was significantly increased.Conclusion:The main active ingredient of rhizoma drynariae,naringin,can reduce the concentration levels of MMP-13 and Syndecan-4 in synovial fluid,improve the structure of articular cartilage injury

关 键 词：柚皮苷 关节软骨损伤 基质金属蛋白酶-13 多配体蛋白聚糖-4 信号通路 

分 类 号：R-33[医药卫生]