二膦酸盐对佐剂性关节炎的影响

Effects of bisphosphonates on adjuvant arthritis

目的观察二膦酸盐对大鼠佐剂性关节炎中关节软骨的影响，探讨其对软骨的保护作用。方法将80只7周龄的Lewis雌鼠随机平均分为对照组（NV）、炎症组（SV）、小剂量（SI10）和大剂量治疗组（SI-100），弗氏佐剂致敏，按10μg／kg和100wg／kg体重每周3次皮下注射英卡膦酸钠。6周和10周时，采用软X线片、组织学染色和末端DNA转移酶介导的脱氧U1P缺口末端标记技术（TUNEL）等方法对前足踝关节进行评估。结果6周时，SV和SI-10关节破坏严重，平均凋亡软骨细胞数分别为（4．23±0．88）个和（3．71±0．74）个，与NV和SI-100差异有统计学意义（P〈0．05）。10周时，SV关节破坏仍很严重，平均凋亡软骨细胞数为（3．84±0．75）个，与其余组差异有统计学意义（P〈0．05）。结论二膦酸盐可以抑制破骨细胞对骨的吸收，保护软骨下骨；还可以抑制软骨细胞的凋亡，保护关节软骨。

Objective To investigate the effects of bisphosphonates on articular cartilage in rat adjuvant arthritis. Methods Eighty seven-week-old female Lewis rats were randomly allocated into normal group （NV）, arthritis group （SV）, low dose （SI-10） and high dose therapy group （SI-100）I Freunds complete adjuvant was used to induce arthritis. The rats in therapy groups were treated with incadronate at 10 or 100 μg/kg subcutaneously three times a week. At 6th and 10th week,the fore-paw joints were evaluated by soft X-rays, toluidine blue staining and TUNEL staining. Results At 6th week, severe articular cartilage destruction and subchondral bone loss were found in SV and SI-10 groups. Apoptotic chondrocyte number in SV group （4,23 ±0.88） and SI-10 group （3.71 ±0.74） was significantly greater than other groups （P 〈0.05）. At 10th week,more severe articular cartilage destruction and greater apoptotic chondrocyte number （ 3.84 ± 0.75 ） were detected in SV group than other groups （ P 〈 0. 05 ）. Conclusion Bisphosphonates can inhibit osteoclast function to protect subchondral bone, and decrease chondrocyte apoptosis to protect articular cartilage in adjuvant arthritis.