百里醌对兔骨关节炎模型关节软骨的保护作用及机制

Protective effects of thymoquinone on cartilage in rabbit osteoarthritis model

目的探索关节腔内注射百里醌对兔骨关节炎模型关节软骨的保护作用及机制。方法选用新西兰大白兔构建动物模型,分为百里醌组、骨关节炎组和假手术组各20只,观察并记录实验大白兔6min内步行距离。术后9周处死动物取左膝关节标本进行大体组织学Gross评分,切片行苏木精-伊红(HE)染色、番红染色后进行组织病理学Mankin评分,采用RT-PCR检测3组大白兔关节软骨中基底金属蛋白酶-13(MMP-13)、基底金属蛋白酶抑制剂-1(TIMP-1)、聚集蛋白聚糖(Aggrecan)和2型胶原(CollagenⅡ)等靶基因表达水平。结果百里醌组大白兔的行走距离明显大于骨关节炎组(P<0.05);而Gross评分、Mankin评分均低于骨关节炎组(均P<0.05)。与骨关节炎组比较,百里醌组MMP-13m RNA表达水平明显下降(P<0.05),TIMP-1、Aggrecan和Colla g e nⅡm RNA表达水平明显上升(均P<0.05)。结论百里醌对兔骨关节炎模型的关节软骨具有保护作用,可以减少疼痛,延缓骨关节炎的进展。百里醌可能通过下调MMP-13m RNA表达,上调TIMP-1、Aggrecan和CollagenⅡm RNA表达的分子机制实现保护作用。

Objective To evaluate the effects of intra-articular injection of thymoquinone on cartilage in rabbit osteoarthritis model. Methods Sixty New Zealand rabbits were randomly divided into treatment group, model group and control group with 20 in each group. Knee osteoarthritis model was established in thymoquinone and model groups, and sham operation was performed in control group, intraarticular injection of thymoquinone was given to treatment group. The walking distance within 6min was observed and recorded. Rabbits were sacrificed and samples of left knees were collected 9 wks after operation. Grosss cores, HE staining, safranin O staining and Mankin score were evaluated. Real-time polymerase chain reactive (PCR) was performed to analysis the mRNA level of MMP-13, TIMP-1, aggrecan, collagenⅡ in cartilage tissue. Results Compared with model group, the thymoquinone group showed better pain related behavior scores (P<0.05). Gross score and Mankin score showed that the cartilage lesions of thymoquinone group were less severe than that of model group. The expression of mmp-13mRNA was lower and the expressions of timp-1, aggrecan and collagen II mRNA were higher in thymoquinone group than those in model group(P<0.05). Conclusion Thymoquinone shows protective effects on cartilage, and can delay the disease progress and improve the pain related behavior scores in rabbit osteoarthritis model, which may be associated with down-regulation of mmp-13 expression and up-regulation of timp-1, aggrecan, collagenⅡexpression.