摘要
目的:探究前期合成的含噻唑烷-4-酮的免疫调节剂CH2b对葡萄糖-6-磷酸异构酶(Glucose-6-phosphate isomerase,GPI)混合肽段诱导的类风湿性关节炎(Rheumatoid arthritis,RA)小鼠发病的影响。方法:h GPI325-339、h GPI469-483多肽片段与完全弗氏佐剂充分乳化后,于DBA/1小鼠尾根部多点皮下注射,并用百日咳毒素加强免疫。然后分别用α-半乳糖神经酰胺(α-Gal Cer)和CH2b对模型小鼠进行干预,监测各组小鼠体重变化和足踝关节肿胀变化情况,关节组织苏木精-伊红(Hematoxylin-eosin staining,HE)染色法观察炎细胞浸润情况,流式细胞技术(Fluorescence-activated cell sorting,FACS)检测全血中i NKT细胞频率变化,微量样本多指标流式蛋白定量技术(Cytometric bead array,CBA)检测血清中细胞因子TNF-α、IL-6、IL-4、IFN-γ水平。结果:与GPI混合肽段诱导的模型组相比,α-Gal Cer和免疫调节剂CH2b均可显著改善模型小鼠的体重增长缓慢、关节肿胀情况(P<0.05);炎性细胞浸润减少;且二者均可以显著提高RA小鼠体内i NKT细胞的频率,与模型组相比,差异有统计学意义(P<0.05);α-Gal Cer、CH2b组可以降低模型小鼠炎症高峰期TNF-α、IL-6、IFN-γ水平,两组结果差异无统计学意义(P>0.05)。结论:免疫调节剂CH2b通过激活i NKT细胞影响炎性细胞因子的分泌,缓解GPI混合肽段诱导的关节炎。
Objective： To explore the effect of the synthetic immunomodulator CH2 b with a thiazolidin-4-one ring on the pathogenesis of rheumatoid arthritis（ RA） mice induced by glucose-6-phosphate isomerase（ GPI） mixed peptides. Methods： h GPI325-339,h GPI469-483 peptide fragments were mixed with complete freund＇ s adjuvant fully,DBA /1 mice were givien subcutaneous injection of the emulsifiers,pertussis toxin to strengthen immunity. And then RA mice were intervened with α-Gal Cer and CH2 b,the changes of body weight,ankle joint symptoms scores were observed. The joint tissues stained with hematoxylin and eosin（ HE） was used to evaluate the inflammatory cells. Fluorescence-activated cell sorting（ FACS） was used to detect the frequency changes of i NKT cells. Cytometric bead array（ CBA） was used to analyze the levels of serum cytokines TNF-α,IL-6,IL-4,IFN-γ. Results： Compared with the model group,α-Gal Cer,CH2 b could reduce the inflammation of the model mice,significantly improve the body weight growth and the joint swelling（ P〈0. 05）. The inflammatory cells infiltration were decreased. More importantly,CH2 b improved the frequency of i NKT cells in peak,the difference was statistically significant（ P〈0. 05）. The levels of TNF-α,IL-6,IFN-γ in serum were significantly decreased（ P〈0. 05） by CH2 b. α-Gal Cer,CH2 b could decrease the levels of TNF-α,IL-6,IFN-γ,and the two groups had no statistically significant difference（ P〉0. 05）. Conclusion： Immunomodulator CH2 b by activating i NKT cells affect the secretion of inflammatory cytokines,and it relieved the GPI induced arthritis.
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2016年第8期1094-1098,共5页
Chinese Journal of Immunology
基金
国家自然科学基金(NSFC)(81373197)
河北省自然科学基金(H2014201133
H2015201131)
河北大学医学学科建设基金(2014A1001
2014A1002)
国家级大学生创新项目基金(201510075030)
