Lnk基因敲除对葡聚糖硫酸钠诱导小鼠结肠炎的影响

张艳青; 华婧; 郭俊荣; 朱明明; 钱佳丽; 徐月节; 许叶旻; 邓彬

doi:10.7619/jcmp.201908002

Lnk基因敲除对葡聚糖硫酸钠诱导小鼠结肠炎的影响

1.
扬州大学医学院病理生理教研室, 江苏扬州, 225009
2.
扬州大学附属医院消化内科, 江苏扬州, 225012

基金项目:

江苏省自然科学基金面上项目 BK20161339

扬州大学大学生学术科技创新基金项目 x2015769

详细信息

通讯作者:
邓彬, E-mail: brightyq@sina.com

中图分类号: R574.62
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出版历程
- 收稿日期: 2019-01-11
- 录用日期: 2019-02-09
- 网络出版日期: 2020-12-03
- 发布日期: 2019-04-27

Effect of Lnk gene knockout on mice with colitis induced by dextran sulfate sodium

1.
Teaching and Research Section of Pathology and Physiology, Medicine School of Yangzhou University, Yangzhou, Jiangsu, 225001
2.
Internal Department of Digestive Medicine, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, 225012

摘要

摘要:
目的比较Lnk基因敲除小鼠与野生型小鼠在葡聚糖硫酸钠(DSS)诱导结肠炎后的表现。
方法将周龄相近的C57BL/6小鼠分为野生型组(WT)、野生型小鼠结肠炎组(WT+DSS)、Lnk敲除鼠组(KO)和Lnk敲除鼠结肠炎组(KO+DSS)。WT和KO小鼠正常饮水, WT+DSS及KO+DSS组小鼠自由饮用2.5% DSS水溶液。实验进行7 d, 每日观察小鼠体质量变化、粪便软硬度及肠道出血情况, 评估疾病活动指数(DAI)。7 d后取外周血，采用流式细胞技术检测WT小鼠和KO小鼠外周血中调节性B细胞(Breg)频率。处死小鼠，取肠观察外形、颜色，测量肠的长度。结肠组织制作为组织学切片，进行HE染色，显微镜下观察组织学改变。
结果 WT和KO组小鼠排便正常, KO+DSS组小鼠与WT+DSS组小鼠较早出现腹泻及排血便情况。KO+DSS组小鼠的体质量在实验周期内较其他3组有显著降低, KO+DSS组DAI随时间显著增加。KO组Breg细胞频率显著低于WT组。KO+DSS组结肠明显变短, HE组织切片镜检糜烂出血、淤血，多病灶浅溃疡，炎性细胞浸润黏膜及黏膜下层并累及肌层，提示炎症反应加重。
结论 Lnk缺失可加重DSS诱导的小鼠结肠炎表现，可能与Lnk KO小鼠体内Breg细胞频率降低、对炎症反应的负调控作用减弱有关。
- Lnk /
- 结肠炎 /
- 调节性B细胞 /
- 疾病活动指数 /
- 结肠组织
Abstract:
Objective To compare the performance of colitis induced by dextran sulfate sodium (DSS) between Lnk-knockout mice and wild-type mice.
Methods The C57BL/6 mice with similar week age were divided into wild type group (WT), wild type mouse with colitis group (WT+DSS), Lnk-knockout group (KO) and Lnk-knockout mouse with colitis group (KO+DSS). WT and KO mice were admitted to drink water freely, WT+DSS and KO+DSS mice was allowed to drink 2.5% DSS aqueous solution freely. The experiment was carried out for 7 days to observe daily weight change, fecal texture (soft or hardness) and intestinal hemorrhage in mice, and to evaluate the disease activity index (DAI). After 7 days, the peripheral blood was collected to detect the regulatory B-cell (Breg) frequency by flow cytometry in the peripheral blood of WT mice and KO mice. The mouse was sacrificed, and the bowel was taken to observe the shape, color and measure the length of the intestine. The colonic tissue was produced by histological sections and HE staining, and histological changes were observed under the microscope.
Results The bowel movement was normal in WT group and KO group, and the mice in KO+DSS group and the WT+DSS group had manifestation of earlier diarrhea and blood-draining. In the experimental period, the weight of KO+DSS group was significantly lower than the other 3 groups, and DAI in the KO+DSS group increased significantly with time. Breg cells frequency in KO group was significantly lower than WT group. In the KO+DSS group, colon obviously shortened, microscopic examination of HE tissue section showed erosive bleeding congestion, multiple lesions shallow ulcer, inflammatory cell infiltration mucosa and submucosa with involvement of the muscle layer, which indicated increased inflammatory response.
Conclusion Lnk deficiency can aggravate the performance of DSS-induced colitis in mice, which may be related to the decrease of Breg cells frequency and negative regulation of inflammatory response in Lnk KO mice.
- Lnk /
- colitis /
- regulatory B-cell /
- disease activity index /
- colon tissue

HTML全文

图 1 各组小鼠体质量变化率

下载: 全尺寸图片幻灯片

图 2 各组小鼠肠的长度

下载: 全尺寸图片幻灯片

图 3 各组肠组织HE染色镜下表现

下载: 全尺寸图片幻灯片

图 4 野生型和Lnk敲除鼠外周血中Breg细胞频率比较

下载: 全尺寸图片幻灯片

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