ISL-β-CD对实验性类风湿性关节炎大鼠血清细胞因子及关节滑膜组织病理改变的影响

The Effects of ISL-β-CD Complex on Serum Cytokines and Synovial Tissue Pathological Changes in Experimental RA Rats

目的研究异甘草素-β-环糊精包合物(isoliquiritigenin-β-cyclodextrin,ISL-β-CD Complex)对Ⅱ型胶原蛋白诱导的类风湿性关节炎(collagen-induced arthritis,CIA)模型大鼠细胞因子水平及关节滑膜组织病理改变的影响。方法将四周龄雄性SD大鼠分为六组,空白对照组、模型对照组,雷公藤多苷片组(100mg·kg-1)和3个不同剂量的ISL-β-CD组(100、400、800mg·kg-1),除空白对照组,其余五组建立CIA模型,自加强免疫第2天灌胃给药4周,末次给药后取血,ELISA法检测血清肿瘤坏死因子TNF-α、白细胞介素(IL)-1β、IL-4、IL-6、IL-10;取关节滑膜,观察关节滑膜病理改变情况。结果与模型对照组相比,ISL-β-CD各个剂量组均能降低大鼠关节肿胀(P<0.05),降低大鼠血清中促炎性细胞因子IL-1β、TNF-α、IL-6的含量(P<0.05),升高抑炎性细胞因子IL-4、IL-10的含量(P<0.05);ISL-β-CD高剂量组对IL-1β、IL-4水平的影响与阳性药物雷公藤多苷片相比差异无统计学意义(P>0.05)。形态学观察ISL-β-CD各个剂量组和雷公藤多苷片组对滑膜细胞增生有显著的抑制作用。结论 ISL-β-CD可通过上调IL-4、IL-10抑炎性细胞因子和下调IL-1β、TNF-α、IL-6促炎性细胞因子而发挥治疗类风湿性关节炎的作用。

Objective To explore the effects of ISL-β-CD on cytokine levels and synovial tissue pathological changes in rheumatoid arthritis（RA） rat model and to provide a new therapy for RA and a new proof for further research.Methods Sixty 4-week-old male SD rats were divided into six groups,as blank control group,model group,glucoside tripterygium group（100mg·kg-1）and three ISL-β-CD groups with different doses（100mg·kg-1,400mg·kg-1,800mg·kg-1）.In addition to the blank control group,all rats were administered by oral once a day for four weeks.After four weeks,all the rats were anesthetized,and blood samples and the synovial tissue of the joint were collected.The levels of IL-1β,TNF-α,IL-6,IL-4 and IL-10 in serum by ELISA were measured and the pathological change of synovial was observed.Results Compared with the model group,ISL-β-CD could reduce joint swelling of rats（P0.05） in each dose group.In ISL-β-CD groups,the level of IL-4,IL-10 in serum increased and the level of IL-1β,TNF-α and IL-6 in serum decreased（P0.05）.In ISL-β-CD and glucoside tripterygium groups,all could inhibit the apoptosis of synovial cells.Conclusion ISL-β-CD play a role in the treatment of rheumatoid arthritis by up-regulating IL-4,IL-10 suppression of inflammatory cytokines and down-regulation of IL-1β,TNF-α,IL-6 proinflammatory cytokines.