盘状结构域受体1对实验性结肠炎小鼠肠道炎症及纤维化的影响

熊彬; 李小丽; 宋飞雪; 李屹; 韩悌云; 张德奎

doi:10.16016/j.2097-0927.202107088

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盘状结构域受体1对实验性结肠炎小鼠肠道炎症及纤维化的影响

基础医学 | 更新时间：2026-01-09

- 盘状结构域受体1对实验性结肠炎小鼠肠道炎症及纤维化的影响
- Effects of discoidin domain receptor 1 on intestinal inflammation and fibrosis in experimental colitis mice
- 陆军军医大学学报 2022年44卷第2期页码：138-146
- 作者机构：
  
  1.730030 兰州，兰州大学第二医院肿瘤内科
  2.730070 兰州，兰州大学口腔医学院
  3.730030 兰州，兰州大学第二医院消化疾病重点实验室
- 作者简介：
  
  [ 张德奎, E-mail: sczdk1972@163.com ZHANG Dekui, E-mail: sczdk1972@163.com
- 基金信息：
  
  甘肃省科技计划项目(18JR3RA321);兰州市城关区科技计划项目(2018SHFZ0043);兰州大学第二医院萃英科技创新计划项目(CY2017-QN10)
- DOI：10.16016/j.2097-0927.202107088
  中图分类号： R341;R394.3;R574.62
- 收稿：2021-07-13，
  
  修回：2021-10-03，
  
  纸质出版：2022-01-30
- 稿件说明：
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熊彬, 李小丽, 宋飞雪, 等. 盘状结构域受体1对实验性结肠炎小鼠肠道炎症及纤维化的影响[J]. 陆军军医大学学报, 2022,44(2):138-146.

Bin XIONG, Xiaoli LI, Feixue SONG, et al. Effects of discoidin domain receptor 1 on intestinal inflammation and fibrosis in experimental colitis mice[J]. Journal of Army Medical University, 2022, 44(2): 138-146.
熊彬, 李小丽, 宋飞雪, 等. 盘状结构域受体1对实验性结肠炎小鼠肠道炎症及纤维化的影响[J]. 陆军军医大学学报, 2022,44(2):138-146. DOI： 10.16016/j.2097-0927.202107088.

Bin XIONG, Xiaoli LI, Feixue SONG, et al. Effects of discoidin domain receptor 1 on intestinal inflammation and fibrosis in experimental colitis mice[J]. Journal of Army Medical University, 2022, 44(2): 138-146. DOI： 10.16016/j.2097-0927.202107088.

摘要

目的

探究盘状结构域受体1(discoidin domain receptors

DDR1)在慢性结肠炎小鼠肠道炎症及肠纤维化中的功能。

方法

针对DDR1基因exon4设计并合成gRNA序列

与编码Cas9的mRNA混合显微注射入C57BL/6小鼠受精卵内，构建DDR1基因突变小鼠。选择F4

代基因敲除纯合子小鼠(DDR1

-/-

) 和野生型C57BL/6小鼠，通过葡聚糖硫酸钠(DSS)诱导慢性结肠炎模型。比较两组小鼠疾病活动指数(DAI)、体质量、结肠长度及组织病理学变化。ELISA法检测外周血细胞因子的含量，Western blot法检测小鼠结肠纤维化相关蛋白表达。

结果

PCR法检测结果显示利用CRISPR/Cas9技术成功构建DDR1

-/-

小鼠；循环饮用DSS后，与野生型小鼠相比，DDR1

-/-

小鼠体质量下降减缓，DAI评分及肠组织病理学评分降低，结肠短缩减轻(5.81±0.11 cm

5.19±0.05 cm，

0.05)；血清IL-1β、TNF-α及TGF-β水平下调(

0.01)；Masson染色胶原容积评分显示肠纤维化减轻(DSS-WT

DSS-DDR1，41.43±0.08 cm

21.37±0.07 cm，

0.01)；肠组织TGF-β、α-SMA和COL1A1的蛋白表达下降。

结论

DDR1参与慢性结肠炎的发生，敲除DDR1基因可减轻慢性结肠炎肠道炎症及纤维化的症状和疾病进程。

Abstract

Objective

To explore the function of discoidin domain receptor 1 (DDR1) in intestinal inflammation and fibrosis in mice with chronic colitis.

Methods

A 20 bp gRNA sequence targeting exon4 of DDR1 gene was designed and synthesized

and subsequently microinjected into the fertilized eggs of C57BL/6 mice after being mixed with Cas9 mRNA in order to generate DDR1 mutant mice. The F4-generation homozygous mice (DDR1

-/-

) as well as wild-type C57BL/6 mice (WT) were used to induce chronic colitis model by being given 2.5% dextran sodium sulfate (DSS) in drinking water. Disease activity index (DAI)

body weight

colon length and histopathological changes were compared between the 2 groups. The contents of pro-inflammatory cytokines in peripheral blood were detected by ELISA. The severity of intestinal fibrosis and the expression of fibrosis related proteins were observed by Masson staining and Western blotting

respectively.

Results

PCR results identified that DDR1

-/-

mutant mice were successfully generated using CRISPR/Cas9 technology. As compared with the WT group

the DDR1

-/-

mice exhibited slower body weight loss

lower DAI scores and intestin

al histopathology scores

and mild colon shortening (5.81±0.11

5.19±0.05 cm

0.05) after DSS drinking. The serum levels of IL-1β

TNF-α and TGF-β were decreased (

0.01)

with down-regulated expression of TGF-β

α-SMA and COL1A1 proteins in the colon tissues of DDR1

-/-

mice. Masson staining displayed that collagen volume fraction was higher in the WT group than the DDR1

-/-

mice (41.43±0.08

21.37±0.07 cm

0.01).

Conclusion

DDR1 is probably involved in the development of chronic colitis

and DDR1 deletion may mitigate the symptoms and disease progression of chronic intestinal inflammation and fibrosis.

关键词

Keywords

references

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