78c对胶原诱导性关节炎小鼠的治疗效果及其机制

THERAPEUTIC EFFECT OF 78c ON MICE WITH COLLAGEN-INDUCED ARTHRITIS AND ITS MECHANISM

目的探讨78c对胶原诱导性关节炎(collagen induced arthritis,CIA)模型小鼠的治疗作用及其机制。方法将18只C57BL/6J小鼠随机分为正常对照组、CIA对照组、CIA治疗组。CIA对照组和CIA治疗组小鼠尾根部皮内均先注射鸡Ⅱ型胶原与弗氏佐剂等量混合液进行模型制备。建模成功后,CIA治疗组小鼠腹腔注射78c 20 mg/kg,正常对照组、CIA对照组小鼠腹腔注射等量溶剂,每周2次,连续给药3周。利用游标卡尺测量各组小鼠足趾厚度;利用苏木精-伊红(HE)染色观察各组小鼠关节组织病理学变化;采用流式细胞仪检测各组小鼠外周血中淋巴细胞亚型、血清中Th1/Th2比值。结果CIA治疗组与CIA对照组相比,足趾厚度显著降低(F=41.38,P<0.05);外周血中NK细胞、CD38+NK细胞比例显著降低(F=5.42、10.21,P<0.05),Treg细胞比例显著升高(F=10.50,P<0.05);血清中Th1/Th2比值显著下降(F=7.67、16.33,P<0.05)。病理检查结果显示,CIA治疗组与CIA对照组相比,滑膜增生程度减轻,炎性细胞浸润减少。结论78c可能通过抑制CD38+NK细胞比例,升高Treg细胞比例,恢复Th1/Th2细胞的平衡对CIA发挥治疗作用。

Objective To investigate the therapeutic effect of 78c on a mouse model of collagen-induced arthritis(CIA)and its mechanism.Methods A total of 18 C57BL/6J mice were randomly divided into normal control group,CIA control group,and CIA treatment group.The mice in the CIA control group and the CIA treatment group were given intradermal injection of a mixed solution of equal volumes of chicken typeⅡcollagen and Freund’s adjuvant at the tail root for modeling.After successful modeling,the mice in the CIA treatment group were given intraperitoneal injection of 78c 20 mg/kg,and those in the normal control group and the CIA control group were given intraperitoneal injection of an equal volume solvent,twice a week for 3 conse-cutive weeks.A vernier caliper was used to measure toe thickness,hematoxylin-eosin staining was used to observe the pathological changes of joint tissue,and flow cytometry was used to measure lymphocyte subsets in peripheral blood and Th1/Th2 ratio in se-rum.Results Compared with the CIA control group,the CIA treatment group had a significant reduction in toe thickness(F=41.38,P<0.05),significant reductions in the percentages of NK cells and CD38+NK cells in peripheral blood(F=5.42,10.21,P<0.05),a significant increase in the percentage of Treg cells in peripheral blood(F=10.50,P<0.05),and a significant reduction in Th1/Th2 ratio in serum(F=7.67,16.33,P<0.05).Pathological results showed that compared with the CIA control group,the CIA treatment group had significant reductions in the degree of synovial hyperplasia and inflammatory cell infiltration.Conclusion 78c may exert a therapeutic effect on CIA by inhibiting the percentage of CD38+NK cells,increasing the percentage of Treg cells,and restoring the balance of Th1/Th2 cells.