热杀死结核分支杆菌H37Ra诱导的SD大鼠佐剂性关节炎模型研究

Research of adjuvant-induced arthritis after mycobacterium tuberculosis H37Ra immunized in SD rats

目的对热杀死结核分支杆菌H37Ra(Mtb)诱导SD大鼠关节炎模型的血液学、T细胞功能、关节滑膜细胞凋亡及病理变化进行分析,以评价该模型与临床RA类疾病的相似性。方法 SD大鼠尾根部一次性皮下注射Mtb-矿物油诱导剂,定期检测大鼠外周血液常规、血液流变学改变;采用流式细胞术测定外周血淋巴细胞凋亡率及调节性T细胞比例;TUNEL法检测关节滑膜细胞凋亡,镜下观察关节滑膜病理改变。结果 SD大鼠经Mtb免疫后,外周血血红蛋白含量下降,血小板总数、红细胞压积上升,全血黏度、血浆黏度上升;外周血淋巴细胞凋亡率明显降低;CD4+CD25+FOXP3+T细胞占CD4+T细胞的比例、CD4+CD25+T细胞占CD4+T细胞的比例均下降;关节滑膜细胞凋亡减少;关节滑膜组织异常增生,有大量炎性细胞浸润,并有肉芽组织形成。结论由Mtb诱导的SD大鼠佐剂性关节炎模型临床表现及组织学改变与临床RA相似,免疫学指标存在明显的细胞免疫异常;该模型制作方法简单、复制成功率高、经济实用,可广泛用于RA的医学研究及抗RA新药筛选。

Aim To analyze the hematology,function of T cell and patho-changes of synovium of AA model induced by Mtb,and estimate the similarity between AA model and RA.Methods AA model was induced with Mtb injection to SD rats,and then the peripheral blood routine,blood rheology,peripheral blood lymphocyte（PBL） apoptosis ratio,regulatory T cells ratio,synoviocyte apoptosis ratio and patho-changes of synovium were objectively recorded.Results After Mtb-immunized adjuvant arthritis in SD rats,the haemoglobin decreased;platelet,hematocrit,blood viscosity and plasma viscosity increased;PBL apoptosis ratio decreased obviously;regulatory T cells ratio of CD4＋CD25＋FOXP3＋ T cells and CD4＋CD25＋ T cells decreased;synoviocyte apoptosis decreased;synovial membrane was hyperplastic,and many inflammatory cells infiltrated,and granulation tissue emerged in it.Conclusions The SD rat AA model induced by Mtb is easy to make and the achievement ratio is high,and its clinical manifestations and histological changes are similar to those of human beings.In addition,this model shows obvious cellular immunological abnormality.To summarize,this method to build an AA model is worth to use widely in RA study and anti-RA drugs research.