Abstract:

Objective To study the preventive effects of soluble egg antigen（SEA）of Schistosomia japonicum on atheroscle?
rosis in ApoE?/? mice and its immune modulatory mechanisms. Methods ApoE?/? mice were divided into an Experimental Group
One and an Experimental Group Two. The mice in the Experimental Group One dividing into a prevention and a control subgroups
were fed with high fat diet since the first week，the mice in the former subgroup were injected intraperitoneally with SEA while
those in the latter one were injected with phosphate buffered saline（PBS）with 1 week interval for 4 times. The mice in the Experi?
mental Group Two were fed with high fat diet for 14 weeks，and then they were divided into a treatment and a control subgroups，
which were injected with SEA and PBS，respectively，since the 14th week with 1 week interval for 4 times. All the mice were
killed in the 22nd week，and the atherosclerosis development and the change of levels of cytokines and CD4+CD25+ FoxP3+T cells
in mice were observed. Results Immunization with SEA led to a significant reduction in the levels of cholesterol，TNF?α，and IL?
10 in all the ApoE?/? mice. The atherosclerosis plaque area of aorta of ApoE?/? mice in the prevention subgroup reduced obviously，
while there was no significant change in the treatment subgroup. In the 22nd week，the proportion of CD4+CD25+ FoxP3+T cells
population in CD4+ T cells was（4.4±0.9）% in the prevention subgroup and there was a significant difference compared with that of
the control subgroup［（2.6±0.3）%］（P < 0.05）. However，the change of the proportion in the treatment subgroup showed no sta?
tistic significance（P > 0.05）. Conclusion The preventive injection of SEA in ApoE?/? module mice has the effect of anti?athero?
sclerosis by increasing the proportion of Treg cells together with the inhibition of inflammatory cytokines at the beginning of disease.

Key words: Schistosoma japonicum；Soluble egg antigen（SEA）；Atherosclerosis；Immune modulation；Cytokine；Treg cells

摘要：

目的探讨日本血吸虫可溶性虫卵抗原（SEA）对ApoE?/?小鼠动脉粥样硬化的保护作用及其免疫调节机制。方法设置实验组1和2，实验组1小鼠从第1周开始高脂饮食喂养，分为预防组和对照组，第1周时分别腹腔注射SEA及PBS，每周1次，共4次；实验组2小鼠高脂饮食喂养至第14周，分为治疗组和对照组，第14周时分别注射SEA及PBS，每周1次，共4次。第22周处死小鼠，观察SEA对动脉粥样硬化的干预作用以及小鼠体内的细胞因子和调节性T 细胞亚CD4+CD25+FoxP3+T细胞水平的变化。结果给予SEA后，与相应对照组比较，预防组和治疗组小鼠血清总胆固醇含量均显著降低，外周血TNF?α、IL?10水平均显著下降；预防组小鼠动脉粥样硬化斑块面积被显著抑制，但治疗组无明显变化。第22周时，预防组外周血CD4+CD25+FoxP3+T细胞占CD4+T细胞比例为（4.4±0.9）%，与对照组［（2.6±0.3）%］相比，差异有统计学意义（P < 0.05）；但治疗组细胞比例给予SEA前后差异无统计学意义（P < 0.05）。结论SEA能降低ApoE?/?小鼠血清总胆固醇水平；预防性给予SEA具有抑制动脉粥样硬化作用，其主要机制是在疾病初始阶段抑制炎症因子产生Treg细胞增殖。

关键词: 日本血吸虫；可溶性虫卵抗原；动脉粥样硬化；免疫调节；细胞因子；调节性T细胞