塞来昔布对大鼠骨关节炎模型关节软骨中TNF-α表达的影响

The effect of Celebrex on the expression of TNF-α in articular cartilage of osteoarthritic rat

目的研究塞来昔布对大鼠骨关节炎模型关节软骨中肿瘤坏死因子-α(TNF-α)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)和塞来昔布治疗组,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(MAI),Western blot方法检测关节软骨中TNF-α蛋白的表达变化,RT-PCR方法检测TNF-αmRNA的表达变化。结果对照组关节无任何异常变化,OA模型组随着造模的时间延长,关节出现了重度红肿现象,与OA模型组比较,给药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TNF-α蛋白及mRNA表达的变化,结果发现TNF-α蛋白及mRNA在对照组大鼠关节软骨仅有微量表达,而在OA组大鼠关节软骨表达则显著升高(P<0.01);与OA组相比,塞来昔布治疗组大鼠关节软骨中TNF-α蛋白及mRNA表达均显著降低(P<0.01)。结论塞来昔布很可通过下调TNF-α的表达参与骨关节炎的发病机制。

Objective To study the effect of Celebrex on the expression of tumor necrosis factor-α（TNF-α）in articular cartilage of osteoarthritic rat model. Methods 30 healthy male Wistar rats were randomly divided into control group （10）, os teoarthritic group （10） and celecoxib treatment group （10）. The model of osteoarthritis was induced with injecting 4% papain so- lution into knee joints. The mean arthritic index was assessed, and the expressions of TNF-ot protein and mRNA was detected by Western blot and RT-PCR methods respectively. Results There was not any 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 gavage in joint of rats in celecoxib treatment group. The expressions of TNF-α protein and mRNA were detected in joint of rats of all group after surgery 8 weeks. We found there were minimal ex- pressions of TNF-α 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 expressions of TNF-α protein and mRNA lower （P〈0.01）. Conclusion One of the mecha- nisms for celeeoxib participate the pathogenesis of OA might be down-regulating were expression of TNF-α.