IL-17单克隆抗体对过敏性紫癜小鼠模型的保护作用及机制

The protective effect and mechanism of IL-17 monoclonal antibody on Henoch-Schonlein purpura mice

为探讨IL-17单克隆抗体(monoclonal antibody,mAb)对过敏性紫癜(Henoch-Schonlein purpura, HSP)小鼠模型的保护作用及机制,50只C57BL/6小鼠被随机分为正常对照组、HSP模型组、同型对照组、IL-17 mAb组以及西咪替丁阳性对照组,每组10只。除正常对照组外,其余4组小鼠均进行为期14周的HSP模型构建,通过检测血清循环免疫复合物(circulating immune complex, CIC)水平验证模型是否构建成功。在建模成功后对各组小鼠进行为期3周的药物干预。干预结束后,收集各组小鼠24 h尿液并进行尿蛋白含量检测;碳粒廓清实验检测小鼠单核巨噬细胞系统(mononuclear phagocytic system, MPS)功能;ELISA检测小鼠血清中分泌型IgE(Secretory-IgE, S-IgE)、IL-17、Th1相关细胞因子IFN-γ以及Th2相关细胞因子IL-4水平;Western blotting检测各组小鼠皮肤和肾脏中IL-17蛋白表达量;HE染色观察小鼠皮肤和肾脏的病理学变化。研究发现,与模型组比较,IL-17 mAb能显著降低HSP小鼠尿蛋白含量(P<0.01);增强HSP小鼠MPS功能(吞噬指数K及吞噬系数α均有P<0.01);降低血清S-IgE、IL-17、IL-4水平(均P<0.01);增加血清IFN-γ水平及IFN-γ/IL-4比值(均P<0.01)。此外,IL-17 mAb还能显著改善HSP小鼠皮肤及肾脏的病理学变化,降低IL-17表达量(P<0.01)。以上结果提示IL-17 mAb对HSP小鼠具有显著的保护作用,其作用机制可能与降低IL-17表达进而影响其调节Th1/Th2免疫平衡有关。

To investigate the protective effect and mechanism of IL-17 monoclonal antibody on Henoch-Schonlein purpura(HSP)mice,50 C57 BL/6 mice were randomly divided into normal control group,HSP model group,isotype control group,IL-17 mAb group and cimetidine positive control group,with 10 mice in each group.4 HSP groups of mice were subjected to a 14-week HSP model construction.We detected the serum circulating immune complex(CIC)to verify whether the model was made successfully.Once we had HSP mice,they were subjected to 3 weeks of drug intervention.After the intervention,24-hour urine volume of each group was collected and the urinary protein content was measured.The function of mononuclear phagocytic system(MPS)was evaluated by the method of carbon particles clearance.The levels of secretory IgE(S-IgE),IL-17,Th1-associated cytokine IFN-γand Th2-related cytokine IL-4 in serum were detected by ELISA.Western blotting was carried out to detect the expression of IL-17 protein in the skin and kidney for each group;HE staining was used to evaluate the pathological changes in the skin and kidney.Our results showed that compared with the HSP group,IL-17 mAb significantly reduced the urine protein content in HSP mice(P<0.01),enhanced MPS function(phagocytic index K and phagocytic coefficientα)(all P<0.01),reduced serum S-IgE,IL-17,IL-4 levels(all P<0.01),increased serum IFN-γlevel and IFN-γ/IL-4 ratio(all P<0.01).In addition,IL-17 mAb significantly improved the pathological changes of skin and kidney in HSP mice and reduced the expression of IL-17 protein(P<0.01).Taken together,IL-17 mAb has a significant protective effect on HSP mice,and its mechanism may be related to the reduction of IL-17 protein expression who mediated Th1/Th2 balance regulation.