吲哚美辛对大鼠骨关节炎模型关节软骨中IL-6表达的影响

目的研究环氧合酶-2(COX-2)抑制剂对大鼠骨关节炎模型关节软骨中白介素-6(IL-6)表达的影响。方法健康雄性Wistar大鼠30只,随机分为对照组、骨性关节炎组(OA组)和COX-2抑制剂(吲哚美辛)处理组,每组10只。利用膝关节注射4%的木瓜蛋白酶溶液的方法制作骨关节炎模型。采用关节炎评分法评定各组大鼠平均关节炎指数,Western blot方法检测关节软骨中IL-6蛋白的表达变化,RT-PCR方法检测关节软骨中IL-6 mRNA的表达变化。结果 OA模型组随着造模时间的延长,关节出现了重度红肿现象,对照组关节无任何异常变化;与OA模型组比较,吲哚美辛组的关节炎症反应呈现消退现象。术后8周检测关节软骨中IL-6蛋白及mRNA表达的变化,结果发现IL-6蛋白及mRNA在对照组大鼠关节软骨中仅有微量表达,而在OA组大鼠关节软骨表达则显著升高(P0.01);与OA组相比,吲哚美辛组大鼠关节软骨中IL-6蛋白表达显著降低(P0.01)。结论吲哚美辛可通过下调IL-6蛋白的表达参与骨关节炎的发病机制。

The effect of cyclooxygenase-2 inhibitor on the expression of IL-6 in articular cartilage of osteoarthritic rat

Objective To study the effect of cyclooxygenase-2 inhibitor on the expression of interleukin-6 （IL-6） in articular cartilage of osteoarthfitic rat. Methods 30 healthy male Wistar rats were randomly divided into control group （n=10）, osteoarthritic group （n= 10） and indomethacin （a kind of cyelooxygenase-2 inhibitor） treatment groups （n=10）. The model of osteoarthritis was induced with injecting 4% papain solution into Knee joints. The mean arthritic index was assessed, and the expression of IL-6 was detected by western blot method, and the level of IL-6 mRNA was detected by RT-PCR method. Results There is no abnormal changes in joint of rats in control group, however, swelling began to appear in joint of rats in OA model group with time sustained ; compared with OA model group, the phenomenon of swelling began to mitigate after celecoxib was garage in treatment group. The expression levels of IL-6 protein and mRNA were detected in joint of rats of all groups 8 weeks after surgery by western blot and RT-PCR methods, respectively. There was minimal expressions of IL-6 protein and mRNA in joint of rats of control group, but increased significantly in joint of rats of OA group ; compared with OA model group, the expression levels of IL-6 protein and mRNA were decreased（P〈0.01 ）. Conclusion One of the mechanisms for indomethacin participate in the pathogenesis of OA might be the down-regulate the expression of IL-6.