口服rhβ2GP1对EAPS小鼠Treg/Th17比率的影响

Effect of oral administration of recombinant human β_2 glycoprotein 1 on Treg / Th17 ratio of mice with experimental anti- phospholipid syndrome

目的:通过口服低剂量抗原(rhβ2GP1)干预EAPS疾病进展过程中小鼠外周血CD4+CD25+Treg和Th17数量和功能变化,探讨EAPS口服耐受机制。方法:ELISA法检测小鼠外周血浆中IL-17、IL-2、IL-6、TGF-β水平变化;计算小鼠流产率(%)、活化部分凝血活酶时间(APTT)和血小板计数(PLT)判断APS病理改变;流式细胞术检测小鼠PBMC中CD4+CD25+Treg及Th17细胞变化。结果:与模型组相比,耐受组小鼠IL-17、IL-2、IL-6水平明显降低,APTT缩短,TGF-β、PLT升高,流产率降低,均差异显著(P<0.05);耐受组小鼠PBMC中CD4+CD25+Treg和Th17细胞百分率及两者的比率与模型组相比差异显著(P<0.05),而与对照组则无差异(P>0.05)。结论:CD4+CD25+Treg/Th17在EAPS口服耐受的诱导中发挥重要作用。

Objective： To explore the oral tolerance mechanism of experimental anti -phospholipid syndrome （EAPS） by interve- ning numerical and functional changes of CIM＋ CD25＋ regulatory T （Treg） and Thl7 in peripheral blood of mice in the course of EAPS pro- gression with oral administration of low- dose recombinant human 132 glycoprotein 1 （rhl3zGP1） . Methods： ELISA was used to detect the changes of interleukin - 17 （ IL - 17 ）, interleukin - 2 （ IL - 2 ）, interleukin - 6 （ IL - 6）, and transforming growth factor - 13 （ TGF - 13） levels in peripheral plasma of mice; the abortion rate, activated partial thromboplastin time （AIYT）, and platelet count （PLT） were calculated ; pathological changes of APS were judged ; flow cytometry was applied to detect the changes of CD4＋ CD25 ＋ Treg and Thl7 cells in pe- ripheral blood mononuclear cells. Results： Compared with model group, the levels of IL - 17, IL -2, and IL -6 in tolerance group decreased significantly （P 〈0. 05） , APTT shortened significantly （P 〈0. 05） , TGF - 13 level and PLT increased significantly （P 〈0. 05） , abortion rate decreased significantly （ P 〈 0. 05 ） ; there were statistically significant differences in the percentages of CD4＋ CD25＋ Treg and Thl7 cells and Treg/Thl7 ratio in peripheral blood mononuelear cells between tolerance group and model group （P 〈 0. 05 ） , compared with control group, there was no statistically significant difference （P 〉 0.05 ） . Conclusion： CD4＋ CD25 ＋ Treg/Th17 ratio plays an important role in induction of oral tolerance in EAPS.