首页|炎症性肠病子代患病的性别差异及其机制研究

炎症性肠病子代患病的性别差异及其机制研究

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目的 探讨炎症性肠病(inflammatory bowel disease,IBD)小鼠子代中患IBD是否存在性别差异.方法 将BALB/c雌鼠随机分为正常对照组(Naïve组)和DSS模型组(DSS组),Naïve组小鼠自由饮用高压灭菌水,DSS组连续饮用2%葡聚糖硫酸钠溶液(dextran sodium sulfate,DSS),7 d后更换为自由饮用高压灭菌水10 d,共进行3~4个循环,同时与健康雄鼠合笼构建IBD母鼠模型.待幼鼠出生后8周,将幼鼠分为Con组和IBD组,Con组自由饮用高压灭菌水7 d,IBD组饮用3%DSS溶液7 d构建IBD模型.造模期间通过每日监测小鼠体重、粪便一致性以及便血情况进行疾病活动指数评分;观察结肠组织的病理切片、杯状细胞和黏液层变化;酶联免疫吸附法检测结肠中白细胞介素-6(interleukin-6,IL-6)、IL-1β、IL-33 和 IL-10 的含量;实时荧光定量 PCR(Real-time quantitative PCR,RT-qPCR)测定结肠中紧密连接蛋白和MUC-2 mRNA表达水平.结果 与IBD雌性小鼠相比,IBD雄性小鼠疾病活动指数评分更高、结肠显著缩短,结肠中出现大量炎性浸润、隐窝异常和杯状细胞缺失的现象,闭合蛋白(occludin,OCLN)的mRNA相对表达量显著降低,IL-6、IL-33水平显著升高、IL-10水平显著下降.结论 IBD小鼠的子代中雄鼠比雌鼠的结肠炎症状更严重,主要与肠道上皮屏障功能严重受损有关.
Effects and mechanisms of sex differences on the prevalence of inflammatory bowel disease in offspring
Objective To investigate whether there are sex differences in inflammatory bowel disease(IBD)among the offspring of mice with IBD.Methods BALB/c female mice were randomly divided into Naïve and DSS groups.The mice in the Naïve group drank autoclaved water freely,and the DSS group freely drank 2%dextran sodium sulfate(DSS)for 7 days before it was replaced with autoclaved water for 10 days.A total of 3~4 cycles were applied,and the IBD female mice were paired with healthy male mice in cages.When the pups were 8 weeks old,they were divided into the Con group and IBD group.The Con group drank autoclaved water freely for 7 days,and the IBD group drank 3%DSS for 7 days.During the modeling period,disease activity index was scored by monitoring body weight,fecal consistency,and the presence of blood in stool every day.Pathological sections were taken to observe changes in goblet cells and the mucus layer of colon tissues.The concentrations of interleukin(IL)-6,IL-1β,IL-33,and IL-10 in the colon were detected by enzyme-linked immunosorbent assay.Real-time quantitative PCR was used to determine the mRNA expression levels of tight-junction proteins and MUC-2 in the colon.Results Compared with female IBD mice,male IBD mice had higher DAI scores,significantly shorter colons,larger amounts of inflammatory infiltrate,more crypt abnormalities,and a higher absence of goblet cells in the colon;their relative mRNA expression of occludin mRNA was significantly reduced,levels of IL-6 and IL-33 were significantly increased,and level of IL-10 was significantly decreased.Conclusions The symptoms of colitis in the offspring of IBD mice were more severe in male than in female mice,a result that was mainly attributed to the more severely impaired intestinal epithelial barrier function in males.

inflammatory bowel diseasecolitisinflammatory responseepithelial barriergut barrier

吴雨泓、陈碧华、吴欢、刘瀚文、欧阳璞玉、孟轩夷、陈红兵

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南昌大学食品科学与资源挖掘全国重点实验室,南昌 330047

南昌大学食品学院,南昌 330047

南昌大学江西省食物过敏重点实验室,南昌 330047

南昌大学中德联合研究院,南昌 330047

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炎症性肠病 结肠炎 炎症反应 上皮屏障 肠道屏障

国家自然科学基金江西省自然科学基金

3210209220224BAB215009

2024

中国实验动物学报
中国实验动物学会,中国医学科学院医学实验动物研究所

中国实验动物学报

CSTPCD北大核心
影响因子:0.767
ISSN:1005-4847
年,卷(期):2024.32(7)
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