旋毛虫副肌球蛋白缓解慢性炎症性肠病的初步研究  

Exploratory study on the ameliorative effects of Trichinella spiralis paramyosin on chronic inflammatory bowel disease

作　　者：吴安琪 骆泽妮 江垚 汪志锴 诸欣平[1] 孙希萌[1] Wu Anqi;Luo Zeni;Jiang Yao;Wang Zhikai;Zhu Xinping;Sun Ximeng(Department of Medical Microbiology and Parasitology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China;Grade 2021 Class Medical Laboratory Testing,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学基础医学院病原生物学系,北京100069 [2]首都医科大学基础医学院,北京100069

出　　处：《首都医科大学学报》2024年第5期891-899,共9页Journal of Capital Medical University

基　　金：北京市自然科学基金面上项目(7222007)。

摘　　要：目的本研究旨在观察旋毛虫副肌球蛋白(Trichinella spiralis paramyosin,Ts Pmy)对于慢性结肠炎的影响。方法首先制备Ts Pmy蛋白,并通过初始T细胞诱导的方法在Rag1 KO小鼠中构建慢性结肠炎模型。随后将Rag1 KO小鼠采用随机数字表法分为3组:接受CD4^(+)Foxp3^(-)CD45RB hi T细胞与Ts Pmy共处理的小鼠组、接受CD4^(+)Foxp3^(-)CD45RB hi T细胞与磷酸盐缓冲液(phosphate buffered saline,PBS)共处理的对照组,以及未经处理的Rag1 KO小鼠组。对小鼠进行腹腔内Ts Pmy预处理,并对其临床症状以及结肠缩短情况进行评估。通过苏木精-伊红染色(hematoxylin-eosin staining,HE)法观察结肠组织以评估炎症情况。此外,通过流式细胞术分析结肠固有层免疫细胞中的辅助性T细胞1(T helper 1 cell,Th1)和辅助性T细胞17(T helper 17 cell,Th17)细胞比例,以及肠道中特异性CD103^(+)耐受性树突状细胞(dendritic cell,DC)的比例。结果Ts Pmy能显著减轻小鼠的体质量下降、疾病活动指数、结肠组织的病理损害以及结肠固有层中炎性Th1和Th17细胞的比例,同时能增加耐受性CD103^(+)DC的丰度。结论Ts Pmy可能通过增加CD103^(+)DC的数量并减少Th1和Th17细胞的比例来缓解慢性结肠炎,显示其具有作为潜在治疗慢性结肠炎的候选分子的可能性。Objective This investigation seeks to discern the effect of Trichinella spiralis paramyosin(Ts Pmy)in modulating chronic colitis.Methods We commenced with the preparation of Ts Pmy,followed by the induction of chronic colitis in Rag1 KO mice via na ve T cells.The subjects Rag1 KO mice were systematically allocated into three groups by random number table:a treatment group receiving CD4^(+)Foxp3^(-)CD45RB hi T cells with Ts Pmy,a control group receiving CD4^(+)Foxp3^(-)CD45RB hi T cells with PBS,and a baseline group consisting of untreated Rag1 KO mice.Mice diagnosed with chronic colitis received intraperitoneal Ts Pmy injections.Subsequent evaluations included assessments of clinical manifestations,colon shortening,and histological examination of colonic inflammation using hematoxylin-eosin(HE)staining.Flow cytometry facilitated the quantitative analysis of T helper 1 cell(Th1)and T helper 17 cell(Th17)cell populations in the colonic lamina propria,alongside the enumeration of gut-specific CD103^(+)regulatory dendritic cells(DCs).Results Administering Ts Pmy conferred a significant attenuation of the weight loss,disease activity index,and pathological damage of colon tissue in mice.Key findings included a marked decrement in the proportions of pro-inflammatory Th1 and Th17 cells and an enhanced presence of immunomodulatory CD103^(+)DCs within the colonic lamina propria.Conclusions Ts Pmy has a mitigating influence on chronic colitis in murine models through the expansion of CD103^(+)DCs and the concurrent reduction of Th1 and Th17 cell populations.These insights pave the way for further investigation into helminth-derived paramyosins as a novel therapeutic strategy for chronic colitis.

关 键 词：旋毛虫副肌球蛋白 免疫机制 慢性结肠炎 CD103^(+)耐受性树突状细胞 

分 类 号：R37[医药卫生—病原生物学]