在IBD患者中,DNase通过释放NET相关蛋白质来加剧肠道微血管损伤
Yiming Shao1,2, Linbin Li2, Yunxi Yang2
1Department of Burns and Plastic Surgery, Affiliated Hospital of Jining Medical University, Jining, China.
概括
在炎症性肠病 (IBD) 中,中性粒细胞外细胞陷 (NETs) 和DNase的增加有助于血管损伤. 向DNase活性可能为IBD治疗提供新的治疗策略.
科学领域:
- 胃肠道学和免疫学
- 血管生物学 血管生物学
- 炎症研究 炎症研究
背景情况:
- 中性细胞外细胞陷 (NETs) 与炎症性肠病 (IBD) 病原发生有关.
- 在IBD中,NET诱导的血管损伤的确切机制尚未完全理解.
研究的目的:
- 调查DNase在IBD中NET介导的血管损伤中的作用.
- 探索IBD相关血管损伤的潜在治疗点.
主要方法:
- 在IBD患者样本 (组织和血液) 中分析NET和DNase,使用免疫光学,ELISA和流细胞计.
- 在DSS诱导的小鼠模型中评估结肠损伤和血管透性.
- 试验室试验评估DNase对血管内皮细胞的影响.
- 使用胺硫酸盐 (GS) 的抑制研究.
主要成果:
- 在IBD患者的结肠中观察到高水平的NETs和DNase.
- 在实验室中,DNase释放了与NET相关的蛋白质,包括MPO,并损坏了血管内皮细胞.
- 在体内,增加的DNase和NET与血管损伤标志物 (CD44,sTM) 相关,并加剧了结肠损伤和血管透性.
- 胺硫酸盐抑制了DNase的活性,减少了NET相关蛋白质的释放,并保护了血管内皮.
- 鉴定出MPO和组织蛋白是血管内皮损伤的关键因素,MPO的基质是H2O2.
结论:
- 在IBD病变中DNase和NET的同步增加导致血管内皮损伤.
- DNase活动在IBD相关的血管损伤中起着重要作用.
- 向DNase为IBD治疗提供了一个有希望的治疗途径.
相关概念视频
01:30Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
334
Various diagnostic tests are employed in the diagnostic process for Inflammatory Bowel Disease (IBD), particularly to differentiate between Crohn's disease and ulcerative colitis.
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
334
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
187
Introduction
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
187
01:17Irritable Bowel Syndrome I: Introduction
277
Irritable Bowel Syndrome (IBS) is characterized by functional disturbances in the gastrointestinal system, presenting a cluster of symptoms without evident structural or biochemical abnormalities. It primarily affects the large intestine and may cause abdominal pain, bloating, excessive gas, diarrhea, constipation, or both.
IBS is a chronic condition that can persist over a long period or recur frequently.
The pathogenesis of IBS involves a complex interplay of the following factors:
Altered...
IBS is a chronic condition that can persist over a long period or recur frequently.
The pathogenesis of IBS involves a complex interplay of the following factors:
Altered...
277
01:17Gastritis-II: Pathophysiology
337
Gastritis is marked by disruption of the mucosal barrier that usually protects the stomach tissue from digestive juices and manifests in acute and chronic forms.
In acute gastritis, the gastric mucosa becomes swollen and red and undergoes superficial erosion. Superficial ulceration may lead to bleeding.
In chronic gastritis, persistent or repeated insults lead to chronic inflammatory changes and, eventually, thinning or atrophy of the gastric tissue.
Gastritis can stem from various causes, each...
In acute gastritis, the gastric mucosa becomes swollen and red and undergoes superficial erosion. Superficial ulceration may lead to bleeding.
In chronic gastritis, persistent or repeated insults lead to chronic inflammatory changes and, eventually, thinning or atrophy of the gastric tissue.
Gastritis can stem from various causes, each...
337
01:30Inflammatory Bowel Disease II: Crohn's Disease
251
Introduction
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
251
01:29Inflammatory Bowel Disease IV: Pharmacological Management
128
Upon diagnosis, managing Inflammatory Bowel Disease (IBD) involves addressing several crucial aspects. The primary goals include resting the bowel, correcting malnutrition, and providing symptomatic relief. Resting the bowel may consist of medications to reduce inflammation and promote healing. Correcting malnutrition is essential, often requiring dietary adjustments and nutritional supplements. Symptomatic relief aims to ease pain, diarrhea, and other discomforts in IBD.
Pharmacologic...
Pharmacologic...
128