伯氏疟原虫抗哌喹系小鼠IFN-γ、TNF-α及IL-4分泌细胞的抗性免疫调控作用  

Effect of IFN-gamma,TNF-alpha and IL-4's secretary cells from a murine model of Plasmodium berghei piperaquine resistant on the resistant related immune regulatory

作　　者：黄宪希[1] 周利民[1] 易国辉[1] 薛伟玲[1] 郭虹[1] 

机构地区：[1]海南医学院科学实验中心,海南海口571199

出　　处：《海南医学院学报》2015年第5期577-581,587,共6页Journal of Hainan Medical University

基　　金：国家自然科学基金(81060140);海南省自然科学基金(30838);海南省科技计划(081009);海南医学院科研启动基金(2011011)~~

摘　　要：目的:通过检测及比较伯氏疟原虫(Pb)ANKA株抗哌喹(PQR)系及敏感(PQS)系感染小鼠脾细胞中γ-干扰素(IFN-γ)、肿瘤坏死因子-α(TNF-α)及白介素-4(IL-4)细胞因子分泌细胞水平的动态变化,探讨哌喹抗性相关免疫调节机制。方法:80只昆明小鼠随机分为A(PbPQS)、B(PbPQR)和C(对照组,NC)3组,应用ELISPOT技术测定各组小鼠脾细胞分泌IFN-γ、TNF-α和IL-4的斑点形成细胞数(SFCs)。结果:在PbPQS或PbPQR感染小鼠后3、6d时IFN-γSFCs A、B两组均显著增高,3d时A组高于B组(P=0.05),而6d时B组明显高于A组(P=0.002),TNF-αSFCs的增加B组明显高于A组(3d:P<0.001,6d:P=0.037),IL-4SFCs A、B两组增高无显著性差别。B组3种细胞因子SFCs 22d间的动态变化结果显示:6d时IFN-γSFCs及TNF-αSFCs增至峰值,9d时IL-4SFCs增至峰值,22d时3种细胞因子SFCs再度增加。结论:感染早期Th1免疫反应的有效活化、其后向Th2免疫反应的偏移以及感染后期3种细胞因子的协同抗原虫作用是影响PbPQR感染小鼠早期原虫增殖低下、其后原虫率上升以及最终疾病转归恢复的重要因素,抗性的产生与宿主免疫密切相关。Objective： To explore the mechanism of malaria piperaquine resistance-associated immunomodulatory by de- tecting and comparing of dynamic changes of IFN-γ.TNF-α and IL-4＇s secreting cells in mice infected with the piperaquine re- sistant （PQR） line and the PQ sensitive （PQS） line of Plasmodium berghei （Pb） ANKA strain. Methods： 80 Kunming mice were divided into three groups of A （PbPQS）, B （PbPQR） and C （normal control, NC） randomly. The numbers of spot form- ing cells （SFCs） of secreting IFN-γ, TNF-α and IL-4 in mice splenocytes were determined by ELISPOTS. Results.. On day 3 and 6 post-PbPQR or PbPQS infection,IFN-γSFCs displayed a significant increase in groups of A and B, it was higher in group A than those in group B （P=0.05） on day 3, but remarkably higher in Group B than those in group A （P=0. 002） on day 6. The increasing TNF-a SFCs were significant higher in group B than those in group A（3 d：P〈0. 001,6 d：P=0. 037）. IL-4 SF- Cs in group A and B were increased with no statistical significance. Dynamic changes of three cytokine-secreting cells in group B during 22 days showed that there was a peak increase in 1FN-γ SFCs, TNF-α SFCs on day 6 past-infection （pi）, IL-4 SFCs on day 9 pi. Three kinds of cytokine SFCs increased again on day 22 pi. Conclusion： Thl immune response activated effectively in early stage of the infection and shifted to the Th2 immune response subsequently, and then synergistic antiprotozoal effects of three cytokines in late period of infection are important influencing factors for suppressing the parasitemia proliferation early, raising parasitemia rate later, and ultimate disease recovery in mice infected with PbPQR. The generation of PbPQR is close related with host immune.

关 键 词：伯氏疟原虫 哌喹抗性 细胞因子 酶联免疫斑点法 

分 类 号：R332[医药卫生—人体生理学]