首页|期刊导航|中国中医骨伤科杂志|甘草酸对骨关节炎大鼠炎症抑制与软骨保护作用

甘草酸对骨关节炎大鼠炎症抑制与软骨保护作用OA

Glycyrrhizic Acid Inhibits Inflammation and Protects Cartilage in Osteoarthritis Rats by the Regulating NF-κB/NLRP3 Pathway

中文摘要英文摘要

目的:探究甘草酸(GA)调节核因子κB(NF-κB)/核苷酸结合寡聚结构域样受体蛋白 3(NLRP3)信号通路对骨关节炎(OA)大鼠炎症反应和软骨细胞凋亡的影响.方法:首先建立骨关节炎大鼠模型,将建模成功的大鼠随机分为 5 组,即骨关节炎组、甘草酸低/中/高剂量组(GA-L 组、GA-M组、GA-H 组)以及高剂量甘草酸+NF-κB/NLRP3 信号通路激活剂 PMA 组(GA-H+PMA 组),另外随机选取等量只进行假手术的 SD大鼠为阴性对照组.检测各组大鼠膝关节肿胀度和被动活动度;检测各组大鼠压痛阈值和热痛阈值;检测各组大鼠血清炎性相关因子及软骨寡聚基质蛋白(COMP)水平变化;检测各组大鼠软骨组织病理及细胞凋亡变化,并进行Mankin评分;检测各组大鼠软骨组织凋亡、基质金属蛋白酶 13(MMP-13)及NF-κB/NLRP3 信号通路相关蛋白表达.结果:骨关节炎组大鼠软骨组织结构破坏严重,软骨细胞减少且排列紊乱,被动活动度、压痛阈值、热痛阈值、Bcl2 低于阴性对照组,膝关节肿胀度、细胞凋亡率、Mankin 评分、IL-18、IL-6、IL-1β、COMP、Bax、MMP-13、p-NF-κB p65/NF-κB p65、NLRP3、Caspase-1 高于阴性对照组,差异有统计学意义(P<0.05);GA-L 组、GA-M组、GA-H 组大鼠软骨组织破坏及软骨细胞损伤减轻,被动活动度、压痛阈值、热痛阈值、Bcl2 高于骨关节炎组,膝关节肿胀度、细胞凋亡率、Mankin 评分、IL-18、IL-6、IL-1β、COMP、Bax、MMP-13、p-NF-κB p65/NF-κB p65、NLRP3、Caspase-1 低于骨关节炎组,差异有统计学意义(P<0.05);GA-H+PMA 组大鼠软骨组织破坏及软骨细胞损伤加重,被动活动度、压痛阈值、热痛阈值、Bcl2 低于 GA-H 组,膝关节肿胀度、细胞凋亡率、Mankin评分、IL-18、IL-6、IL-1β、COMP、B ax、MMP-13、p-NF-κB p 65/NF-κB p 65、NLRP3、Caspase-1 高于GA-H 组,差异有统计学意义(P<0.05).结论:甘草酸可能通过抑制 NF-κB/NLRP3 信号通路,减少骨关节炎大鼠炎症反应和软骨细胞凋亡,延缓骨关节退化.

Objective:To investigate the effects of glycyrrhizic acid(GA)on inflammatory response and chondrocyte apop-tosis in osteoarthritis(OA)rats via regulation of the nuclear factor-κB(NF-κB)/nucleotide-binding oligomerization do-main-like receptor protein 3(NLRP3)signaling pathway.Methods:Firstly,osteoarthritis rats were established,Then the successfully modeled rats were randomly separated into five groups:OA group,GA low,medium,and high dose groups(GA-L group,GA-M group,GA-H group),and GA high-dose+NF-κB/NLRP3 signaling pathway activator PMA group(GA-H+PMA group).In addition,an equal number of SD rats undergoing sham surgery were randomly considered as the negative control(NC)group.The knee joint swelling and passive range of motion in rats from each group were measured.The tenderness threshold and thermal pain threshold of rats were determined.The changes in serum levels of inflamma-tory-related factors and cartilage oligomeric matrix protein(COMP)were detected in rats.The pathological and apop-totic changes of cartilage tissue in rats were detected by Mankin score.The apoptosis of cartilage tissue,the expression of matrix metalloproteinase-13(MMP-13)and NF-κB/NLRP3 signaling pathway related proteins were detected in each group.Results:The cartilage tissue structure of rats in the OA group was severely damaged,with reduced and disordered arrange-ment of chondrocytes.The passive range of motion,tenderness threshold,thermal pain threshold,and Bcl2 were lower than those in the NC group,and the knee joint swelling,cell apoptosis rate,Mankin score,IL-18,IL-6,IL-1β,COMP,Bax,MMP-13,p-NF-κB p65/NF-κB p65,NLRP3,and Caspase-1 were higher than those in the NC group(P<0.05).The destruction of cartilage tissue and damage to chondrocytes in rats in the GA-L group,GA-M group,and GA-H group were reduced,the passive range of motion,tenderness threshold,thermal pain threshold,and Bcl2 were higher than those in the OA group,and the knee joint swelling,cell apoptosis rate,Mankin score,IL-18,IL-6,IL-1β,COMP,Bax,MMP-13,p-NF-κB p65/NF-κB p65,NLRP3,and Caspase-1 were lower than those in the OA group(P<0.05).The destruction of cartilage tissue and damage to chondrocytes in rats in the GA-H+PMA group were aggravated,the passive range of motion,tenderness threshold,thermal pain threshold,and Bcl2 were lower than those in the GA-H group,and the knee joint swelling,cell apoptosis rate,Mankin score,IL-18,IL-6,IL-1β,COMP,Bax,MMP-13,p-NF-κB p65/NF-κB p65,NLRP3,and Caspase-1 were higher than those in the GA-H group(P<0.05).Conclusion:Glycyrrhizic acid may inhibit the NF-κB/NLRP3 signaling pathway to reduce inflammation and chondrocyte apoptosis in osteoar-thritis rats,and delay bone and joint degeneration.

安梦宇;帕提麦·马秉成;艾则孜·艾海提;孟晓源;张浩沙强;宁凯

新疆维吾尔自治区人民医院(乌鲁木齐,830000)新疆维吾尔自治区人民医院(乌鲁木齐,830000)新疆维吾尔自治区人民医院(乌鲁木齐,830000)新疆维吾尔自治区人民医院(乌鲁木齐,830000)新疆维吾尔自治区人民医院(乌鲁木齐,830000)新疆维吾尔自治区人民医院(乌鲁木齐,830000)

医药卫生

甘草酸核因子κB/核苷酸结合寡聚结构域样受体蛋白3骨关节炎炎症细胞凋亡

glycyrrhizic acidNF-κB/NLRP3osteoarthritisinflammationapoptosis

《中国中医骨伤科杂志》 2026 (4)

7-13,7

新疆维吾尔自治区人民医院院内项目(20230209)

10.20085/j.cnki.issn1005-0205.260402

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