[1]张畅,汤萨,宗雪,等.不同日龄乳鼠感染EV71毒株后组织免疫学特征实验研究[J].现代检验医学杂志,2026,41(05):40-45+51.[doi:10.3969/j.issn.1671-7414.2026.05.007]
　ZHANG Chang,TANG Sa,ZONG Xue,et al.Experimental Study on Tissue Immunological Characteristics of Suckling Mice of Different Ages Infected with EV71 Strain[J].Journal of Modern Laboratory Medicine,2026,41(05):40-45+51.[doi:10.3969/j.issn.1671-7414.2026.05.007]
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不同日龄乳鼠感染EV71毒株后组织免疫学特征实验研究()

《现代检验医学杂志》[ISSN:/CN:]

卷:
第41卷
期数:
2026年05期
页码:
40-45+51
栏目:
论著
出版日期:
2026-09-15

文章信息/Info

Title:
Experimental Study on Tissue Immunological Characteristics of Suckling Mice of Different Ages Infected with EV71 Strain
文章编号:
1671-7414 （2026） 05-040-07
作者:
张畅，汤萨，宗雪，石有伟，连捷，王云帆
（北京大学首钢医院病理科，北京100144）
Author(s):
ZHANG Chang, TANG Sa, ZONG Xue, SHI Youwei, LIAN Jie, WANG Yunfan
(Department of Pathology, Peking University Shougang Hospital, Beijing 100144, China)
关键词:
肠道病毒71型毒株;  组织免疫学;  免疫细胞;  乳鼠日龄
分类号:
R-332； R373.25； R392.11
DOI:
10.3969/j.issn.1671-7414.2026.05.007
文献标志码:
A
摘要:
目的 探讨不同日龄乳鼠感染肠道病毒71型 （EV71） 后的组织病理表现、 免疫细胞分布及细胞因子表达特征。 方 法 选取7、 14、 18及21日龄乳鼠， 经腹腔注射EV71 GD10-12株建立感染模型， 动态监测其存活率、 体重变化及临床评 分； 通过组织学检查观察骨髓、 胸腺等免疫器官结构成熟度； 采用流式细胞术检测感染前后小肠组织中3型先天性淋巴细 胞 （ILC3s） 及CD4+ T细胞、 CD8+ T细胞等免疫细胞的比例与数量； 利用实时荧光定量聚合酶链式反应 （RT-qPCR） 检测感染 前后白细胞介素-1β （IL-1β） 、 白细胞介素-22 （IL-22） 、 白细胞介素-23 （IL-23） 及肿瘤坏死因子-α （TNF-α） 基因的相对表 达量。 结果 EV71感染后， 乳鼠死亡率随日龄增大显著降低 （χ2 =29.15， P＜0.001） ： 7日龄3 天内全死， 14日龄4 天内全死， 18日龄7 天内全死， 21日龄无死亡。 体重变化显示， 7～18日龄乳鼠体重增长停滞或死亡前下降， 21日龄乳鼠体重持续正 常增长 （F=73.82， P＜0.001） ； 临床评分显示， 7～18日龄乳鼠快速升至3～5分且严重阶段持续2～3天， 21日龄乳鼠仅升 至1～2分， 感染后8天恢复至0分 （F=4.633， P=0.017） 。 组织学显示， 随日龄增长免疫器官逐渐成熟， 18～21日龄接近成年 小鼠特征。 免疫细胞检测显示， 7～21日龄小肠各免疫细胞 （除NK细胞外） 比例差异逐渐扩大： 与低日龄乳鼠比较， CD4+ T 细胞、 CD8+ T细胞、 γδT细胞比例显著升高， B细胞、 DC细胞比例显著降低 （F=38.861~847.276， 均P＜0.001） 。 与同组感 染前比较， 7～18日龄感染后ILC3s数量显著减少 （t=5.828、 5.854、 4.611， 均P＜0.05） ， 21日龄感染后ILC3s数量显著增加 （t=-4.032， P=0.016） 。 细胞因子检测显示， 感染前IL-1β、 TNF-α随日龄增加逐渐降低 （F=264.322、 104.483， 均P＜0.05） ， IL-22、 IL-23随日龄增加逐渐升高 （F=176.101、 180.815， 均P＜0.05） ；与同组感染前比较， 感染后7～21日龄IL-1β （t= -136.593~-12.890）及14～21日龄TNF-α （t=-38.505~-25.589）均显著升高 （均P＜0.001） ， 14～21日龄IL-22 （t=36.316、 15.083、 8.778） 及7～21日龄IL-23 （t=5.362~74.642） 均显著降低 （均P＜0.001） 。 结论 不同日龄乳鼠感染EV71后的组织免 疫学特征存在显著差异， 乳鼠对EV71感染的抵抗力随日龄增长而增强， 该过程与免疫器官成熟、 ILC3s动态调控及细胞 因子网络平衡密切相关。
Abstract:
Objective To investigate the histopathological manifestations, immune cell distribution and cytokine expression pro- ?les in suckling mice of different ages following Enterovirus 71 (EV71) infection. Methods Suckling mice aged 7, 14, 18, and 21 days were selected to establish infection models by intraperitoneal injection with EV71 strain GD10-12. Survival rate, body weight changes, and clinical scores of the mice were dynamically monitored. Histological examination was performed to evaluate the structural maturity of immune organs such as bone marrow and thymus. Flow cytometry was used to detect the proportions and numbers of type 3 innate lymphoid cells (ILC3s), CD4+ T cells, CD8+ T cells, and other immune cell subsets in the small in- testine before and after infection. Quantitative real-time polymerase chain reaction (RT-qPCR) was employed to determine the relative expression levels of interleukin-1β (IL-1β), interleukin-22 (IL-22), interleukin-23 (IL-23) and tumor necrosis factor-α (TNF-α) before and after infection. Results After EV71 infection, mortality rates of suckling mice signi?cantly decreased with increasing age (χ2 =29.15, P<0.001): all 7-day-old mice died within 3 days, all 14-day-old mice died within 4 days, all 18-day-old mice died within 7 days, whereas no 21-day-old mice died. Body weight was arrested or declined before death in 7~18-day-old mice, while 21-day-old mice maintained normal weight gain (F=73.82, P<0.001). Clinical score in 7~18-day-old mice rapidly increased to 3~5 points and remained at severe levels for 2~3 days, whereas 21-day-old mice only reached scores of 1-2 and re- covered to 0 by day 8 post-infection (F=4.633, P=0.017). Histological results revealed progressive maturation of immune organs with age, with 18-21-day-old mice displaying features close to those of adult mice. Immune cell pro?ling showed that the differ- ences in the proportion of various immune cells in the small intestine of 7~21-day-old mice gradually expanded, except for NK cells: compared with younger suckling mice, the proportions of CD4+ T cells, CD8+ T cells, and γδT cells were signi?cantly in- creased, while the proportions of B cells and dendritic cells were signi?cantly decreased (F=38.861~847.276, all P<0.001). Com- pared with pre-infection evels within the same age group, ILC3 levels signi?cantly decreased after infection in 7~18-day-old mice (t=5.828, 5.854, and 4.611, respectively; all P<0.05), but signi?cantly increased in 21-day-old mice (t=-4.032, P=0.016). Cytokine detection showed that pre-infection expression of IL-1β and TNF-α gradually decreased with age (F=264.322, 104.483, both P<0.05), whereas IL-22 and IL-23 gradually increased (F=176.101, 180.815, both P<0.05). After infection, IL-1β levels in 7~21-day-old mice (t=-136.593 to -12.890) and TNF-α levels in 14~21-day-old mice (t=-38.505 ~ -25.589) were signi?cantly increased (all P<0.001), while IL-22 levels in 14~21-day-old mice (t=8.778 ~ 36.316) and IL-23 levels in 7~21-day- old mice (t=5.362~74.642) were signi?cantly decreased (all P<0.001). Conclusions Signi?cant age-dependent differences in tis- sue immunological characteristics are observed in EV71-infected suckling mice. Resistance to EV71 infection increases with age, a process closely associated with immune organ maturation, dynamic regulation of ILC3s, and cytokine network balance.

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备注/Memo

备注/Memo:
基金项目：北京大学首钢医院首颐医疗科技发展基金（项目编号：SGYYQ202404）。
作者简介：张畅（1988-），女，博士，主治医师，研究方向：肠道免疫微环境，E-mail：zhangchang0605@163.com。
通讯作者：王云帆（1978-），女，硕士，主任医师，研究方向：消化系统肿瘤，E-mail：wangtaozyy@126.com。
更新日期/Last Update: 2026-09-15