雷公藤甲素对佐剂性关节炎大鼠核因子κB受体激活剂配基表达的影响

Effect of triptolide on expression of receptor activator of nuclear factor-κB ligand in rat adjuvant induced arthritis

目的探讨雷公藤甲素对佐剂性关节炎(AA)大鼠核因子κB受体激活剂配基(RANKL)和护骨素(OPG)表达的影响及其与抑制关节炎大鼠骨侵蚀的关系。方法AA大鼠经雷公藤甲素治疗后,测定关节中RANKL、OPG的表达,并测定外周血单个核细胞(PBMC)RANKLmRNA的表达水平和外周血中肿瘤坏死因子(TNF)-α和白细胞介素(IL)-1#水平,同时测定胫骨关节端骨密度,并作关节骨侵蚀病理积分。结果雷公藤甲素组和甲氨蝶呤组骨密度高于模型组(P<0.01),关节骨侵蚀积分低于模型组(P<0.01)。雷公藤甲素组大鼠关节滑膜(P<0.01)及骨组织(P<0.05)RANKL表达量低于模型组,滑膜OPG表达量低于模型组(P<0.05)。雷公藤甲素组PBMC中RANKLmRNA表达水平低于模型组(P<0.01),并且TNF-α和IL-1$水平低于模型组(P<0.01)。结论雷公藤甲素可能通过抑制RANKL表达而抑制AA大鼠骨质侵蚀。未见雷公藤甲素对OPG表达有促进作用。

Objective To explore the effect of triptolide （TP） on expression of receptor activator of nuclear factor-κB ligand （RANKL） and osteoprotegerin （OPG） in rat adjuvant induced arthritis （AA）. Methods AA was induced in Wistar rats. Arthritis rats were treated with TP and methotrexate （MTX） at the onset （day 9） of arthritis. On the peak of arthritis （day 24）, the expression of RANKL and OPG protein in the joints and RANKL mRNA in peripheral blood monoeuclear cell （PBMC） were analyzed. TNF-α,IL-1β levels in peripheral blood were determined. Bone mineral density （BMD） and bone erosion scores were also evaluated. Results Compared with AA group, arthritis rats treated with TP had higher BMD, lower bone erosion scores （P〈0.01） and lower levels expression of RANKL in the synovium （P〈0.01） and bone （P〈0.05） and lower OPG level in synovium （P〈0.05）. TP might also decrease RANKL mRNA expression in PBMC （P〈0.01） and TNF-α,IL-1β levels in peripheral blood （P〈0.01）. Conclusion TP may inhibit rat adjuvant arthritis bone erosion by deceasing the expression of RANKL in inflammatory joints.