高迁移率族蛋白B1/Toll样受体9途径在重症急性胰腺炎肠黏膜屏障损伤中的作用及机制分析

蒲玟静; 赵宏贤; 柏超; 周翔宇; 陈霞

doi:10.3969/j.issn.1001-5256.2019.05.020

高迁移率族蛋白B1/Toll样受体9途径在重症急性胰腺炎肠黏膜屏障损伤中的作用及机制分析

DOI: 10.3969/j.issn.1001-5256.2019.05.020

1. 西南医科大学附属医院消化内科
2. 西南医科大学组胚教研室
3. 西南医科大学附属医院血管外科

基金项目:

泸州市政府-四川医科大学合作项目[2015LZYD-S04(3/15)]；国家自然科学青年基金(81600420)；

详细信息

中图分类号: R576
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出版历程
- 收稿日期: 2019-01-28
- 出版日期: 2019-05-20

Role and mechanism of the high-mobility group box 1/Toll-like receptor 9 signaling pathway in intestinal mucosal barrier injury in severe acute pancreatitis

Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University

Research funding:

摘要

摘要: 目的探讨高迁移率族蛋白B1（HMGB1）、Toll样受体（TLR） 9信号通路在重症急性胰腺炎（SAP）小鼠肠黏膜屏障损伤中的作用机制。方法将20只KM小鼠随机分为对照组和SAP组,每组10只。SAP组小鼠采用雨蛙素及脂多糖联合腹腔内注射建模,12 h后取材。HE染色观察小鼠胰腺病理学变化; ELISA检测小鼠血清二氨氧化酶（DAO）和内毒素核心抗体（Endo CAb）水平; TUNEL法检测小鼠小肠黏膜凋亡变化; Western Blot检测各组小鼠小肠HMGB1、TLR9、NF-κB蛋白水平的变化。计量资料2组间比较采用t检验。结果 SAP组小鼠均造模成功。SAP组小鼠血清DAO和EndoCAb水平明显高于对照组,差异有统计学意义（12. 172±1. 356 vs 4. 341±0. 521、32. 480±3. 054 vs 13. 281±2. 105,t值分别为16. 613、14. 725,P值分别为<0. 001、0. 025）; SAP组小鼠小肠黏膜细胞凋亡较对照组明显增加,差异有统计学意义（6. 25±2. 10 vs 19. 54±3. 63,t=11. 5...
- 胰腺炎,急性坏死性 /
- 肠黏膜 /
- HMGB1蛋白质 /
- Toll样受体9 /
- NF-κB /
- 小鼠 /
- 动物实验
Abstract: Objective To investigate the role and mechanism of the high-mobility group box 1 ( HMGB1) /Toll-like receptor 9 ( TLR9) signaling pathway in intestinal mucosal barrier injury in mice with severe acute pancreatitis ( SAP) . Methods A total of KM mice were randomly divided into control group and SAP group. The mice in the SAP group were given intraperitoneal injection of cerulein and lipopolysaccharide to establish a model of SAP, and the samples were collected at 12 hours after modeling. HE staining was used to observe the pathological changes of the pancreas; ELISA was used to measure the serum levels of diamine oxidase ( DAO) and endotoxin core antibody ( EndoCAb) ; TUNEL was used to observe the apoptosis of intestinal mucosal cells; Western Blot was used to measure the changes in the protein expression of HMGB1, TLR9, and nuclear factor-kappa B ( NF-κB) in the small intestine. The t-test was used for comparison of normally distributed continuous data between two groups. Results A mouse model of SAP was successfully established. Compared with the control group, the SAP group had significantly higher serum levels of DAO ( 12. 172 ± 1. 356 vs 4. 341 ± 0. 521, t = 16. 613, P < 0. 001) and EndoCAb ( 32. 480 ± 3. 054 vs 13. 281 ± 2. 105, t = 14. 725, P = 0. 025) . Compared with the control group, the SAP group had a significant increase in apoptotic intestinal mucosal cells ( 19. 54 ± 3. 63 vs 6. 25 ± 2. 1, t = 11. 582, P < 0. 05) . Compared with the control group, the SAP group had significantly higher protein expression of HMGB1 ( 0. 590 ± 0. 004 vs 0. 059 ± 0. 035, t = 47. 336, P = 0. 001) , TLR 9 ( 0. 530 ± 0. 043 vs 0. 070 ± 0. 023, t = 30. 565, P = 0. 034) , and NF-κB ( 0. 670 ± 0. 059 vs 0. 170 ± 0. 032, t = 23. 655, P =0. 014) . Conclusion There is an increase in the expression of HMGB1 in the intestine of SAP mice, which may play an important role in intestinal mucosal barrier injury by activating the downstream TLR9 signaling pathway.
- pancreatitis, acute necrotizing /
- intestinal mucosa /
- HMGB1 protein /
- Toll-like receptor 9 /
- NF-kappa B /
- mice /
- animal experimentation

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参考文献(14)

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