复原益肾汤对类风湿关节炎大鼠白细胞介素-17、肿瘤坏死因子-α及基质金属蛋白酶-3的影响

Effects of recovery and benefiting kidney（R&B） soup on interleukin-17，tumor necrosis factor-α and matrix metalloproteinase-3 in rats with rheumatoid arthritis

摘要:

目的：观察复原益肾汤对Ⅱ型胶原诱导的关节炎大鼠滑膜组织病理改变及相关细胞因子表达的作用，探讨复原益肾汤治疗类风湿关节炎（rheumatoid arthritis，RA）的潜在机制。方法：以Ⅱ胶原诱导大鼠RA模型，设正常组、模型组、甲氨蝶呤（methotrexate，MTX）组、复原益肾汤高中低剂量组，测算大鼠足肿胀率；酶联免疫吸附试验法检测血清肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）和白细胞介素-17（interleukin-17，IL-17）水平；免疫组化法检测软骨和滑膜基质金属蛋白酶-3（matrix metalloproteinase-3，MMP-3）水平；光镜观察大鼠足关节滑膜组织病理学变化。结果：复原益肾汤高剂量组及MTX组的RA大鼠关节炎症积分较模型组有显著降低（F=156.671，P=0.000）；中药高、中剂量组及MTX组血清中TNF-α、IL-17均有显著降低（TNF-α：F=20.233，P=0.000；IL-17：F=205.412，P=0.000），中药高剂量组与MTX组之间无统计学差异（TNF-α：P=0.952；IL-17：P=0.142）；中药高剂量组和MTX组中软骨层及滑膜层MMP-3较模型组有显著降低（F=14.867，P=0.000），中药高剂量组与MTX组之间无统计学差异（P=0.08）。结论：复原益肾汤可改善关节炎大鼠的病理损伤，其作用机制与抑制TNF-α、IL-17、MMP-3等炎症介质的表达密切相关，为复原益肾汤治疗类风湿关节炎提供了科学依据。

Abstract:

Objective：To determine the effects of recovery and benefiting kidney soup（R&B，a capsule containing several Chinese herbs）on pathology changes of synovial tissues and expressions of related cytokines in rats with type Ⅱ collagen induced arthritis （CIA） and to further discuss the possible mechanism of R&B soup treatment for rheumatoid arthritis（RA）. Methods：RA in SD rats was induced using cattle collagen Ⅱand the rats were divided into normal group，model group，methotrexate（MTX） group，large，medium and small doses of R&B soup groups. Rat feet swelling rates were calculated；serum tumor necrosis factor-α（TNF-α） and interleukin-17（IL-17） levels were detected by ELISA；synovial matrix metalloproteinase-3（MMP-3） levels were detected by im－munohistochemistry assay；light microscopic was used to observe rat feet joint synovial tissues pathological changes. Results：In－flammatory scores of RA were significantly decreased in high dose R&B soup group and MTX group compared with those of model group（F=156.671；P=0.000）. Serum TNF-α and IL-17 levels were also significantly decreased in high，medium dose R&B soup groups and MTX group（TNF-α：F=20.233，P=0.000；IL-17：F=205.412，P=0.000）；no significant difference in serum TNF-α and IL-17 was observed between high dose R&B soup group and MTX group（TNF-α：P=0.952；IL-17：P=0.142）. MMP-3 levels in cartilage and synovium were significantly decreased in high dose R&B soup group and MTX group than in model group（F=14.867；P=0.000）；there was no difference in MMP-3 levels in cartilage and synovium between high dose R&B soup group and MTX group（P=0.08）. Conclusions：R&B soup is revealed to alleviate pathological damages of RA rats through inhibiting the expressions of TNF-α，IL-17，MMP-3 and other inflammatory mediators，which provide scientific proofs for treating RA with R&B soup.