高选择性非甾体抗炎药塞来昔布对大鼠骨关节炎关节软骨的影响

Effects of highly selective NSAIDs on osteoarthritic cartilage in experimental rat model

目的探讨长期应用高选择性NSAIDs(塞来昔布)对大鼠骨关节炎关节软骨代谢的影响。方法采用左侧跟腱切除术诱发Wistar大鼠同侧膝关节骨关节炎(OA),分4组,每日给赛来昔布24mg/kg(CE组)、布洛芬72mg/kg(IBP组)、吲哚美辛9mg/kg(IN组)及生理盐水(NS组)。观察3、6及9个月后关节软骨组织学、蛋白多糖(PG)含量、Ⅱ型胶原表达及软骨细胞超微结构的变化。结果CE、NS组软骨表现为OA的渐进过程,CE组改变较NS组轻;IN组软骨损害明显重于NS组;IBP组介于两者之间。CE明显增加OA软骨基质PG含量;IBP的短、中期应用对PG的含量无明显影响,其长期应用减少PG含量;IN明显减少PG含量。CE、IBP促进OA软骨细胞Ⅱ型胶原的表达,IN抑制Ⅱ型胶原的表达。电镜观察:CE组、NS组的软骨细胞表现类似,但CE组可见发达的粗面内质网、高尔基复合体;IBP组:细胞周晕逐渐消失,核染色质结构模糊;IN组:软骨细胞的电子密度明显增加、溶解性坏死多见。结论塞来昔布可抑制大鼠OA关节软骨的退变,对退变的关节软骨可能有一定的修复作用。

[Objective] To investigate the potential effects of Celecoxib on osteoarthritic cartilage in the experimental rat model, [Methods] The left knee osteoarthritis was induced after surgery two months later by the excision of the left achilles tendon. Wistar rats were randomly divided into 4 groups, CE, IBP, IN and NS group. Celecoxib was given at dosage of 24 mg/kg·day. Ibuprofen （72 mg/kg ·day） and indomethcin （9 mg/kg·day） were given. The rats were sacrificed in batches 3, 6 and 9 months after the procedures. [Results] Celecoxib had favourable action on OA progression by increasing the matrix component synthesis, inhibiting the degradation of chondrocytes, increasing the synthesis of proteoglycan and collagen type Ⅱ. Ibuprofen inhibited the matrix component synthesis and increased the degradation of proteoglycan and the synthesis of collagen type Ⅱ. Indomethacin caused the damage of chondrocytes and erosion of articular cartilage, and suppressed the synthesis of proteoglycan and collagen type Ⅱ. [Conclusion] Celecoxib may has some beneficial influences on the articular cartilage in the experimental rat model, and may be the drugs of choice in the treatment of chronic destructive joint disease where anti-inflammatory drugs need to be used for a prolonged period.