异甘草素-β-环糊精包合物对CIA大鼠Cyclin D1表达的影响

Effects of ISL-β-CD Complex on the Expression of Cyclin D1 in Rats with Collagen Induced Arthritis

目的:研究异甘草素-β-环糊精包合物(isoliquiritigenin-β-cyclodextrin complex,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)模型大鼠体重、血清氧化指标、关节滑膜细胞凋亡及关节滑膜中细胞周期蛋白D1(Cyclin D1)表达的影响,进一步探讨ISL-β-CD包合物治疗CIA模型大鼠的机制。方法:将四周龄雄性SD大鼠分为6组,空白对照组、模型对照组,雷公藤多苷片组(100 mg.kg-1)和3个不同剂量的ISL-β-CD组(100 mg.kg-1,400 mg.kg-1,800 mg.kg-1),除空白对照组,其余5组建立CIA模型,自加强免疫第二天灌胃给药4周,每周测量大鼠体重,末次给药后取血和关节滑膜,检测血清中氧化指标超氧化物歧化酶(SOD)和丙二醛(MDA)水平,TUNEL计算关节滑膜细胞凋亡、western blot检测滑膜细胞中cyclinD1的表达。结果:与模型对照组相比,ISL-β-CD能改善类风湿性关节炎带来的体重降低(P<0.05),降低大鼠血清中SOD水平(P<0.05),升高MDA水平(P<0.05);药物治疗组的细胞凋亡率高于模型对照组;但经过药物治疗后,滑膜中cyclin D1的水平没有降低。结论:ISL-β-CD包合物可促进细胞凋亡改善RA症状而不是通过作用于cyclin D1降低细胞过度增殖改善RA症状。ISL-β-CD包合物可作为治疗RA的潜在药物进一步被开发研究而其作用于RA的机制有待进一步探讨。

Objective： To study the effects of ISL-β-CD Complex on the Rats with Collagen Induced Arthritis,including weights,levels of Superoxide Dismutase（SOD） and malondialdehyde（MDA）,apoptosis of synoviocytes and expressions of cyclin D1 in Synovium of joint.To investigate the mechanism of treating that ISL-β-CD complex on CIA model.Methods： Rats were randomly divided into 6 groups： normal control group,CIA model group,high-dose ISL-β-CD complex group,middle-dose ISL-β-CD complex group,low-dose ISL-β-CD complex group,and total glucoside tripterygium group.Rats in the five groups,except the normal control group,established to be CIA model.The intragastric administration procedure was performed from the first day after boosting immunization once a day for four weeks.Weights were recorded every week.The blood and synovium of joint were taken after the last administration.Levels of serum SOD and MDA were measure,apoptosis of synoviocytes was counted with TUNEL,and the expression of cyclin D1 was detect by western-blot.Results： ISL-β-CD complex could improve the reduction of weight（P0.05）,decrease the level of SOD（P0.05）,increase the level of MDA（P0.05）,reduce the apoptosis of synoviocytes（P0.05） compared with the CIA model group.But our complex could not cut down the expression level of cyclin D1.Conclusion： ISL-β-CD complex is able to improve the symptom of RA which is caused by promoting the apoptosis,not by the action on cyclin D1.ISL-β-CD Complex could be taken further studied as a potential medicine for RA.