玻璃酸钠对兔骨关节炎早期iNOS炎症途径及炎性细胞因子表达影响的实验研究

摘要

目的 探讨骨关节炎(OA)早期病理生理变化中一氧化氮合酶(iNOS)、一氧化氮(NO)和炎症性细胞因子(如TNF-α、IL-1β、IL-6、和IL-17)表达水平的相关性,以及玻璃酸钠腔内注射对OA早期iNOS炎症途径和炎性细胞因子的影响.方法 48只新西兰大白兔随机分为三组,分别为空白对照组、模型组和玻璃酸钠治疗组,模型组和玻璃酸纳治疗组前交叉韧带切断制备兔膝骨关节炎软骨退行性病变(ACLT)模型.造模四周后玻璃酸钠治疗组给予玻璃酸钠0.3 mg/(只·次),关节内重复注射每周一次,连续4周.模型组以相同方式注射等体积的生理盐水.造模8周后处死动物,行关节腔大体观察、软骨组织学观察;采用试剂盒检测血清和关节腔内iNOS、NO的表达量;采用ELISA法对关节腔内TNF-α、IL-1p、IL-6、和IL-17等细胞因子进行检测.结果 经玻璃酸钠治疗4周后,血清和关节腔内iNOS、NO和TNF-α、IL-1β、IL-6、以及IL-17的表达量显著性下降,且具有一定相关性;HE染色和病理学评分结果表明,玻璃酸钠治疗软骨能显著改善关节软骨的退变进程.结论 在OA早期的发病历程中,NO的合成与炎症性细胞因子表达呈正相关,且玻璃酸钠可能通过抑制iNOS途径来阻断NO的产生,发挥保护关节软骨的作用.%Objective To investigate the correlation between the production of NO,iNOS and the expressions of TNF-α、IL-1β、IL-6 and IL-17 in the articular cartilage of rabbits with traumatic osteoarthritis (OA),and to explore the influence of Sodium hyaluronate (SH) on cartilage degeneration in traumatic OA.Methods 48 New Zealand rabbits underwent anterior cruciateligament transaction (ACLT) of the right knee and then were divided into three groups.The animals in the SH-treatment group were injected with SH (0.3 mg) in the knees 4 week after operation,once a week for 4 weeks.Rabbits in the model group were treated with normal saline under the same condition and the control group does nothing.All rabbits were sacrificed after the last treatment.Cartilagineus changes ofthe medial femoral condyles were grossly checked and OA severity was evaluated under light-microscope-The concentration of NO and iNOS in joint fluid,serum and the expressions of TNF-α、IL-1 β、IL-6 and IL-17 in joint fluid were assessed ELISA kit.Results The results of HE staining and pathological score show that cartilage degeneration in the SH-treatment group was significantly slighter than that in the model group.The concentration of NO and iNOS in joint fluid,serum and the expressions of TNF-α、IL-1β 、IL-6 and IL-17 in joint fluid were significantly lower than those in the model group (P＜0.01) after SH treatment.Conclusion The expression of NO was positively correlated with inflammatory Cytokines in the early stages of OA.And SH may protect articular cartilage by inhibiting synthesis of NO.