外源性IL⁃25对日本血吸虫感染引起肠壁损伤的影响  

Role of IL⁃25 in gut damage induced by Schistosoma japonicum infection

作　　者：孙思宇 杨宇轩 陈璐[1] 倪杨玥 常浩[1] 陈琳[1] 侯敏[1] 徐志鹏[1] 熊春蓉[2] 杨坤[2] 季旻珺[1] SUN Siyu;YANG Yuxuan;CHEN Lu;NI Yangyue;CHANG Hao;CHEN Lin;HOU Min;XU Zhipeng;XIONG Chunrong;YANG Kun;JI Minjun(Department of Pathogen Biology,Nanjing Medical University,Jiangsu Province Key Laboratory of Modern Pathogen Biology,Nanjing 211166;Jiangsu Institute of Parasitic Diseases,Wuxi 214064,China)

机构地区：[1]南京医科大学病原生物学系,江苏省现代病原生物学重点实验室,江苏南京211166 [2]江苏省血吸虫病防治研究所,江苏无锡214064

出　　处：《南京医科大学学报（自然科学版）》2023年第4期452-458,474,共8页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81971965,82272368);国家自然科学基金青年基金(81903621)。

摘　　要：目的:探究外源性白细胞介素(interleukin,IL)⁃25对日本血吸虫感染所致小鼠肠壁损伤的影响。方法:24只雌性C57BL/6J小鼠随机分为正常组、正常+IL⁃25组、感染组、感染+IL⁃25组。感染组、感染+IL⁃25组中每只小鼠感染日本血吸虫尾蚴40条;感染+IL⁃25组、正常+IL⁃25组小鼠于感染后或实验开始后第4周开始腹腔注射IL⁃25(0.5μg/只,隔天注射1次,持续3周)。感染6周后剖杀小鼠,取肝脏和肠组织制作病理切片,苏木素伊红(hematoxylin⁃eosin,HE)染色后观察小鼠肝脏、结肠病理学变化,阿尔新蓝⁃过碘酸雪夫(Alcian blue⁃periodic acid⁃Schiff,AB⁃PAS)染色观察小鼠结直肠内杯状细胞数量变化;酶联免疫吸附试验(enzyme⁃linked immunosorbent assay,ELISA)、实时荧光定量试验(real⁃time polymerase chain reaction,real⁃time PCR)检测小鼠结肠部位炎症相关因子IL⁃10、IL⁃4、IL⁃13、肿瘤坏死因子⁃α(tumor necrosis factorα,TNF⁃α)、γ干扰素(interferonγ,IFN⁃γ)和IL⁃1β等的表达水平。结果:感染6周后的肠组织HE染色结果显示,日本血吸虫感染后,结直肠部位出现虫卵堆积,但是在经过IL⁃25注射之后,肠道损伤减轻,虫卵堆积减少;感染+IL⁃25组小鼠肠道单个肉芽肿面积显著低于感染组小鼠,但是感染组小鼠肝脏肉芽肿面积与感染+IL⁃25组小鼠无明显区别;AB⁃PAS结果显示IL⁃25能够显著增加日本血吸虫感染小鼠肠道杯状细胞数量;ELISA、real⁃time PCR结果显示感染日本血吸虫后小鼠结肠1型、2型细胞因子均有不同程度的升高,且在注射IL⁃25之后,呈现2型细胞因子表达量上升、1型细胞因子表达量下降的趋势。结论:IL⁃25可通过促进杯状细胞分化缓解日本血吸虫感染所致的肠壁损伤。Objective:To investigate the effects of exogenous interleukin(IL)⁃25 in gut damage in mice caused by Schistosoma japonicum(S.japonicum)infection.Methods:Twenty⁃four female C57BL/6J mice were randomly divided into four groups,control group(n=5),control+IL⁃25(n=5),S.japonicum infection group(Inf,n=7),S.japonicum infection+IL⁃25 group(Inf+IL⁃25,n=7).Mice in the Inf group and Inf+IL⁃25 group were infected with forty S.japonicum cercariaes.IL⁃25 was intraperitoneally injected from the 4th week after infection(0.5μg/mice every 2 days for 3 weeks).Six weeks after infection,mice were sacrificed.Hematoxylin eosin(HE)staining was performed in the liver and colon tissue to observed the pathological changes.Alcian blue⁃periodic and acid⁃Schiff(AB⁃PAS)staining was performed to observe the number of goblet cells in the colon.The levels of inflammation⁃related cytokines including IL⁃10,IL⁃4,IL⁃13,tumor necrosis factorα(TNF⁃α),interferonγ(IFN⁃γ),IL⁃1βin the colon were detected by enzyme linked immunosorbent assay(ELISA)and real⁃time polymerase chain reaction(real⁃time PCR).Results:HE staining results showed that the area of individual granulomas in the colon in the Inf+IL⁃25 group was significantly lower than that of mice in the Inf group,but the area of granulomas in the liver in the Inf group was not significantly different from that in the Inf+IL⁃25 group.The results of AB⁃PAS staining showed that IL⁃25 could significantly promote the number of colonic goblet cells in mice after infection with S.japonicum,the ELISA and the real⁃time PCR results showed that cytokines in the colon after S.japonicum infection were obviously altered,and IL⁃25 injection promoted the expression of type 2 cytokines and decreased the expression of type 1 cytokines.Conclusion:IL⁃25 can alleviate the gut damage induced by S.japonicum infection by promoting the differentiation of goblet cells.

关 键 词：日本血吸虫 肠壁损伤 IL⁃25 

分 类 号：R383.2[医药卫生—医学寄生虫学]