无菌炎症诱导血管病变和慢性肺损伤在小鼠状细胞疾病
Kevin R Rarick1, Keguo Li2, Ru-Jeng Teng3
1Department of Pediatrics, Division of Critical Care, Medical College of Wisconsin, Milwaukee, WI, 53226, USA; Childrens' Research Institute, Children's Wisconsin, Milwaukee, WI, 53226, USA.
Free radical biology & medicine
|February 9, 2024
概括
高流动性组盒-1 (HMGB1) 和S-酸氨酸还原酶 (GSNOR) 驱动状细胞疾病 (SCD) 的并发症. 针对这些分子进行HE-HMGB1-BP或KYC等疗法可能会减少SCD患者的血管病变和肺损伤.
科学领域:
- 生物医学研究生物医学研究
- 血管生物学 血管生物学
- 肺部医学 肺部医学
背景情况:
- 鼠状细胞病 (SCD) 导致多器官损伤,主要是通过血管病变.
- 氧化的生物可用性和无菌炎症与SCD血管病变有关.
- 高流动性组盒-1 (HMGB1),一种与损伤相关的分子模式 (DAMP),是血管损伤的潜在调解者.
研究的目的:
- 为了研究HMGB1对状细胞疾病 (SCD) 的小鼠内皮依赖血管扩张和肺结构的影响.
- 在SCD模型中评估向HMGB1和S-尼特罗斯格氨酸还原酶 (GSNOR) 的治疗潜力.
主要方法:
- 在SCD的小鼠模型中,用酸盐缓冲盐水 (PBS),He-HMGB1-BP,N6022或N-乙-lysyltyrosylcysteine amide (KYC) 进行了治疗.
- 评估了对血HMGB1,动脉和肺中的GSNOR表达,内皮依赖血管扩张和肺形态学的影响.
- 人类静脉内皮细胞 (HUVEC) 用重组HMGB1 (r-HMGB1) 进行治疗,以研究GSNOR表达.
主要成果:
- HMGB1直接增加了内皮细胞中的GSNOR表达.
- 用 hE-HMGB1-BP 治疗降低了血HMGB1和GSNOR表达,改善了SS小鼠的血管扩张和肺结构.
- 此外,N6022和KYC治疗也分别改善了血管扩张和肺形态学.
结论:
- 鼠类SCD通过一个依赖于HMGB1和GSNOR的机制诱导血管病和慢性肺病.
- 准HMGB1和GSNOR代表了一种有前途的治疗策略,用于减轻SCD中的血管病变和肺部疾病.
相关概念视频
01:20Chronic Obstructive Pulmonary Disease-II: Pathophysiology
5.0K
Chronic Obstructive Pulmonary Disease (COPD) pathophysiology is intricate and multifaceted, involving a complex interplay of physiological processes. Understanding these mechanisms is crucial for effectively managing and treating COPD. Here is an in-depth look at the critical elements in the pathophysiology of COPD:
Chronic Inflammation
Chronic Inflammation
5.0K
01:24Chronic Obstructive Pulmonary Disease III: Chronic Bronchitis Features
40
Chronic bronchitis is a key phenotype of chronic obstructive pulmonary disease (COPD), characterized by airway-centered inflammation and mucus overproduction. It develops from long-term exposure to harmful particles or gases, most commonly cigarette smoke, which triggers a persistent inflammatory response.Cellular and Structural ChangesInflammation initially affects the large bronchi and later the smaller airways, with infiltration by immune cells, including neutrophils, macrophages, and...
40