龙胆苦苷对创伤性骨关节炎大鼠关节软骨的保护作用机制研究

Pro tective Mechanism of Gentiopicroside on Articular Cartilage of Rats with Traumatic Osteoarthritis through NF-κB Signaling Pathway

目的探讨龙胆苦苷通过核转录因子-κB(NF-κB)信号通路对创伤性骨关节炎大鼠关节软骨的保护作用机制。方法将30只雄性SD大鼠根据随机数字表法分为对照组、模型组和龙胆苦苷治疗组。模型组和龙胆苦苷治疗组制作大鼠创伤性骨关节炎模型,对照组只切开关节腔,在造模1周后对龙胆苦苷治疗组大鼠灌胃给予龙胆苦苷溶液,对照组和模型组给予等量蒸馏水,连续8周,进行病理学检测和Mankin评分,检测软骨组织中一氧化氮(NO)和肿瘤坏死因子-α(TNF-α)含量以及NF-κB和NF-κB抑制蛋白(I-κB)蛋白的水平。结果龙胆苦苷治疗组膝关节软骨组织在变性、坏死方面均较模型组轻;与对照组比较,模型组和龙胆苦苷治疗组Mankin评分、大鼠膝关节软骨组织中NO和TNF-α含量、大鼠膝关节软骨组织中NF-κB蛋白水平增加,大鼠膝关节软骨组织中I-κB蛋白水平降低(P<0.05);与模型组比较,龙胆苦苷治疗组Mankin评分、大鼠膝关节软骨组织中NO和TNF-α含量、大鼠膝关节软骨组织中NF-κB蛋白水平降低,大鼠膝关节软骨组织中I-κB蛋白水平增高(P<0.05)。结论龙胆苦苷能够改善创伤性骨关节炎大鼠关节软骨的形态、降低软骨组织中NO和TNF-α含量,减轻软骨退变,其机制可能与降低了NF-κB蛋白水平,增加了I-κB蛋白水平有关。

Objective:To investigate protective mechanism of gentiopicroside on articular cartilage of rats with traumatic osteoarthritis through nuclear factor κB(NF-κB) signaling pathway. Methods:30 male SD rats were divided into control group,model group and gentiopicroside group according to the random number table method. Rats in the model group and gentiopicroside group were used to establish the traumatic osteoarthritis model. While the rats in control group only had the articular cavity exposed. 1 wk after model establishment,the rats in the gentiopicroside group were given 50 mg/kg gentiopicroside solution by gavage,and the same amount of distilled water was given to the control and model groups once a day for 8 weeks. Thereafter,the Pathological examination and Mankin score were performed. The levels of nitric oxide(NO) and tumor necrosis factor-α(TNF-α) in articular cartilage tissues as well as the levels of NF-κB and inhibitor of NF-κB(I-κB) were detected. Results:The degeneration and necrosis degree were more mild in the gentiopicroside group than in the model group;The Mankin score as well as higher levels of NO,TNF-α,and NF-κB among three groups in a descending order was the model group,gentiopicroside group and control group,while the I-κB level among three groups in an ascending order was model group,gentiopicroside group and control group groups (P < 0.05). Conclusion:Gentiopicroside can ameliorate the morphology of articular cartilage in rats with traumatic osteoarthritis,decrease the content of NO and TNF-α in cartilage tissue,and reduce cartilage degeneration. The mechanism may relate to the decreasing level of NF-κB protein and increasing level of I-κB protein.