日本血吸虫源多肽SJMHE1通过调节脾脏IFN-γ和IL-10的分泌抑制小鼠自身免疫性甲状腺炎

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摘要目的：探讨日本血吸虫源多肽SJMHE1对小鼠自身免疫性甲状腺炎（autoimmune thyroiditis，AIT）的干预作用及其分子机制。方法：将15只6~8周龄雌性C57BL/6小鼠随机分为对照组、AIT模型组和AIT+SJMHE1组，每组5只。对照组小鼠未经任何处理；采用高碘水喂食和皮下多点注射猪甲状腺球蛋白法构建AIT小鼠模型（AIT模型组），并施加SJMHE1干预（AIT+SJMHE1组）。造模28 d后，苏木素伊红（HE）染色观察各组小鼠甲状腺病理变化；化学发光法检测血清甲状腺球蛋白抗体（TgAb）水平；实时荧光定量PCR检测各组小鼠甲状腺及脾脏组织中IFNγ和IL10 mRNA的表达水平；ELISA检测血清中IFNγ和IL10含量。另选取未经任何处理的10只雌性C57BL/6小鼠，随机分为实验组和对照组，每组5只；实验组小鼠皮下输注FITC标记的SJMHE1（FITCSJMHE1），对照组注射等量PBS，用流式细胞技术检测FITCSJMHE1在甲状腺及脾脏组织中的分布。结果： SJMHE1可减轻AIT小鼠甲状腺组织炎症细胞浸润及滤泡结构破坏，且显著降低血清TgAb水平(P<0.01)；此外，SJMHE1显著降低AIT小鼠甲状腺组织和脾脏组织中IFN-γ mRNA的表达，而上调IL-10 mRNA的相对表达量(P均<0.05)；且血清中IFN-γ和IL-10含量的改变趋势与mRNA一致(P<0.01和P<0.05)。流式细胞技术结果显示FITCSJMHE1分布于小鼠脾脏组织。结论： SJMHE1可显著抑制AIT小鼠甲状腺炎症反应，其机制可能与其对脾脏IFN-γ和IL-10的调节有关。

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Abstract： Objective： To investigate the intervention effect and mechanism of SJMHE1, a peptide derived from Schistosoma japonicum, on autoimmune thyroiditis (AIT) mice. Methods： Fifteen female C57BL/6 mice aged 6~8 weeks were randomly divided into control group, AIT model group and AIT+SJMHE1 group, with five mice in each group. Control group mice were without any treatment; the AIT mouse model (AIT model group) was established by feeding with high iodine water and subcutaneous multipoint injection of porcine thyroglobulin; and SJMHE1 was administered to AIT+SJMHE1 group. After 28 days of modeling, Hematoxylineosin (HE) staining was used to observe the pathological changes of thyroid in mice. The expression of thyroglobulin antibody (TgAb) in serum of mice was detected by chemiluminescence. The expression levels of IFNγ and IL10 mRNA in thyroid and spleen tissues of mice were detected by realtime quantitative PCR. Serum IFNγ and IL10 were detected by ELISA. Another 10 female C57BL/6 mice without any treatment were divided into experiment group and control group, with five mice in each group. FITC-labeled SJMHE1 (FITC-SJMHE1) was injected subcutaneously into mice of experimental group, and equal amount of PBS was injected into mice of control group. The distribution of FITC-SJMHE1 in thyroid and spleen tissues was detected by flow cytometry. Results： SJMHE1 significantly reduced the infiltration of inflammatory cells and damage of follicular structure in thyroid tissue of AIT mice, as well as the level of TgAb in serum (P<0.01). In addition, SJMHE1 significantly decreased IFN-γ mRNA expression and upregulated IL-10 mRNA relative level in the thyroid and spleen tissue of AIT mice (P<0.05). The results were consistent with the levels of IFN-γ and IL-10 in serum of mice (P<0.01 and P<0.05). Flow cytometry showed that FITC-SJMHE1 was only distributed in mouse spleen. Conclusion： SJMHE1 can significantly reduce thyroid pathology in AIT mice, which may be related to the regulation on IFNγ and IL10 in spleen.

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收稿日期: 2022-07-23

基金资助: 国家自然科学基金资助项目（81370889，81900562）

通讯作者: 毛朝明（通讯作者），副教授，博士生导师，E-mail: jq1001@ujs.edu.cn

作者简介: 张珊（1998—），女，硕士研究生；

引用本文:

张珊，毛朝明，董利阳，等.. 日本血吸虫源多肽SJMHE1通过调节脾脏IFN-γ和IL-10的分泌抑制小鼠自身免疫性甲状腺炎[J]. 江苏大学学报:医学版, 2023, 33(01): 37-41. ZHANG Shan, MAO Chaoming, DONG Liyang, LIU Jiameng, ZHENG Tingting, GAO Xuerong, XU Xiaowei, LUO Xinkai, WANG Xuefeng. Schistosoma japonicum polypeptide SJMHE1 alleviates autoimmune thyroiditis

in mice by regulating IFN-γ and IL-10 in the spleen

. Journal of Jiangsu University(Medicine Edition), 2023, 33(01): 37-41.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2023/V33/I01/37

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