透骨消痛胶囊干预膝骨性关节炎软骨下骨重塑的分子机制

背景:前期研究表明透骨消痛胶囊能有效治疗膝骨性关节炎,且对膝关节软骨有保护作用,软骨下骨重塑在骨性关节炎病理进程中起重要作用。目的:观察透骨消痛胶囊干预骨性关节炎软骨下骨重塑的作用及并探讨其作用机制。方法:新西兰大白兔分为正常组、模型组、壮骨关节丸组、透骨消痛胶囊组4组。除正常组外动物均按改良Hulth法造模。正常组、模型组兔每天给予生理盐水灌胃;壮骨关节丸组兔每天给予壮骨关节丸水溶液灌胃;透骨消痛胶囊组兔每天给予透骨消痛胶囊水溶液灌胃。结果与结论:造模后6,9,12周,透骨消痛胶囊组软骨下骨CyclinD1基因、胰岛素样生长因子1、细胞核因子κB受体活化因子配体mRNA表达均显著高于正常组(P<0.05)。与模型组比较,造模后1周,透骨消痛胶囊组Cyclin D1 mRNA表达较低(P<0.05);造模后6周,透骨消痛胶囊组细胞核因子κB受体活化因子配体表达较低(P<0.05);造模后9,12周,透骨消痛胶囊组各项指标表达均较低(P<0.05)。与壮骨关节丸组比较,造模1周后,透骨消痛胶囊组Cyclin D1 mRNA表达较低(P<0.05);6周时透骨消痛胶囊组细胞核因子κB受体活化因子配体表达较低(P<0.05);9,12周后,透骨消痛胶囊组胰岛素样生长因子1mRNA表达较低(P<0.05)。提示透骨消痛胶囊可改变软骨下骨重塑的速率和模式,最终减轻软骨下骨硬化。

Molecular mechanism of Tougu Xiaotong capsules for subchondral bone remodeling in knee Osteoarthritis

BACKGROUND:Former study indicates that Tougu Xiaotong capsule is an effective treatment for knee osteoarthritis;it has a protective effect on knee articular cartilage.Subchondral bone remodeling is important in the pathology process of knee osteoarthritis.OBJECTIVE:To observe the effect of Tougu Xiaotong capsule on subchondral bone remodeling in osteoarthritis and to investigate the mechanism.METHODS:New Zealand rabbits were divided into four groups:normal group,model group,Zhuanggu Guanjie pill group and Tougu Xiaotong capsule group.Model construction was performed using modified Hulth method in rabbits except for the normal group.Rabbits in the normal group and model group were administrated with normal saline daily by gavage.Rabbits in the Zhuanggu Guanjie pill group were administrated with the water solution of Zhuanggu Guanjie pill by gavage daily.Rabbits in Tougu Xiaotong capsule group were administrated the water solution of Tougu Xiaotong capsule by gavage daily.RESULTS AND CONCLUSION:The expression of Cyclin D1 gene,insulin-like growth factor and receptor activator of nuclear factor-κB ligand mRNA in the subchondral bone of the Tougu Xiaotong capsule group was significantly higher than that of the normal group in 6,9 and 12 weeks after mo del construction(P < 0.05).Compared with the model group,the mRNA expression of Cyclin D1 in the Tougu Xiaotong capsule group was lower in 1 week after model construction(P < 0.05);the mRNA expression of insulin-like growth factor and receptor activator of nuclear factor-κB ligand was lower in 6 week after model construction(P < 0.05);the expression of indicators in the Tougu Xiaotong capsule group was relatively lower in 9 and 12 week after model construction(P < 0.05).Compared with Zhuanggu Guanjie pill group,the expression of Cyclin D1 mRNA in the Tougu Xiaotong capsule group was lower in 1 week after model construction(P < 0.05);the expression of receptor activator of nuclear factor-κB ligand in the Tougu Xiaotong capsule group was lower in 6 week after model construction(P < 0.05);the mRNA expression of insulin-like growth factor in the Tougu Xiaotong capsule group was lower in 9 and 12 weeks(P < 0.05).These findings indicate that Tougu Xiaotong capsule can change the rates and patterns of subchondral bone remodeling,and ultimately reduce the subchondral bone sclerosis.