在两种CKD模型中,慢性环境低氧减弱了先天免疫激活和损伤
Fernanda Florencia Fregnan Zambom1, Amanda Helen Albino1, Helena Mendonça Tessaro1
1Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
American journal of physiology. Renal physiology
|July 13, 2023
概括
慢性低氧 (低氧) 在慢性病 (CKD) 模型中意外保护脏. 这一发现挑战了缺氧会恶化CKD的观点,并提出了新的保护策略.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 生理学 生理学 生理学
- 病理生理学 病理生理学
背景情况:
- 组织缺氧被认为是慢性病 (CKD) 进展的主要驱动因素.
- 然而,现有的证据显示,缺氧在CKD发病过程中的作用存在不一致.
- 以前的研究表明,慢性缺氧不会导致损伤,甚至在某些模型中减轻了损伤.
研究的目的:
- 在慢性病 (CKD) 的两个不同的模型中研究慢性低环境氧气暴露的保护作用.
- 在腺因诱导和氧化物抑制的CKD模型中,探索正常环境低氧对损伤和炎症的影响.
- 阐明潜在的机制,包括炎症途径和氧化应激,参与缺氧介导的保护.
主要方法:
- 利用了两种已知慢性病 (CKD) 的老鼠模型:腺过量和慢性氧化抑制.
- 给CKD模型大鼠进行了慢性normobaric环境低氧 (低环境Po2).
- 评估了损伤,炎症,NF-κB和炎症酶激活,氧化应激和血管素II透.
主要成果:
- 持续暴露于低环境氧气显著减弱损伤和炎症,在腺因诱导和氧化物抑制的CKD模型中.
- 发现缺氧会限制关键炎症途径的激活,包括NF-κB和NLRP3炎症体.
- 缺氧还减少了氧化应激和血管素II阳性细胞的内透,这可能是由缺氧诱导因子 (HIF) - 2α激活的介导.
结论:
- 长期暴露在低环境氧气下,在多种慢性病 (CKD) 模型中显示出显著的保护作用.
- 这些发现挑战了传统的缺氧理解,认为缺氧在CKD中仅仅是有害的.
- 保护机制包括抑制炎症,氧化应激和激活适应性缺氧反应,这表明CKD的新疗法.
相关概念视频
01:25Chronic Kidney Disease I: Introduction
41
Chronic Kidney Disease (CKD) arises when the kidneys progressively lose their ability to function, ultimately leading to end-stage kidney disease (ESKD). At this advanced stage, the kidneys can no longer filter waste or maintain essential body functions, requiring renal replacement therapy (RRT) through dialysis or a kidney transplant for survival.Early-stage chronic kidney disease and detection challengesIn CKD's early stages, symptoms often remain absent because healthy nephrons compensate...
41
01:24Chronic Kidney Disease II: Clinical Manifestations
35
Chronic Kidney Disease (CKD) progressively impairs multiple body systems due to the accumulation of uremic toxins, which disrupt cellular functions across various organs.Neurologic symptomsNeurologic symptoms often arise early in CKD, as uremic toxin buildup drives changes in cognitive and motor functions. Patients frequently experience fatigue, headache, confusion, difficulty concentrating, and, in severe cases, seizures. Peripheral neuropathy commonly manifests as burning sensations in the...
35
01:29Acute Kidney Injury II: Pathophysiology
34
Acute kidney injury (AKI) causes are categorized into three primary categories based on the location of the injury: prerenal, intrarenal (or intrinsic), and postrenal causes. This classification guides clinical management and illustrates how different pathways can impair kidney function.Etiology and Pathophysiology of Acute Kidney Injury1. Prerenal causesEtiology: Prerenal Acute Kidney Injury, the most common type, occurs when reduced blood flow to the kidneys decreases filtration capacity...
34
01:28Chronic Kidney Disease III: Interprofessional Care
43
Chronic kidney disease (CKD) requires collaborative and comprehensive management. CKD progresses through stages and can lead to end-stage kidney disease (ESKD) if untreated. Interprofessional collaboration and patient education are crucial, enabling patients to manage their health and improve their quality of life.Diagnostic approach for chronic kidney diseaseThe diagnosis of CKD primarily focuses on the glomerular filtration rate (GFR), which assesses kidney function by measuring how well...
43
01:22Acute Kidney Injury I: Introduction
34
Introduction:Acute Kidney Injury (AKI) describes a swift decrease in kidney function occurring over hours to days, characterized by the kidneys' failure to remove waste products from the bloodstream. This leads to dangerous complications like metabolic acidosis, fluid overload, and electrolyte imbalances, such as hyperkalemia, which can cause life-threatening arrhythmias. AKI is common in both hospital and outpatient settings, often triggered by dehydration, sepsis, or exposure to nephrotoxic...
34
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
36
Accurate diagnosis and effective prevention are critical in managing Acute Kidney Injury (AKI), which is linked to high mortality rates ranging from 10% to 80%. Timely recognition of at-risk patients and careful monitoring can significantly reduce the likelihood of kidney damage.Diagnostic Assessments:The diagnostic process starts with a comprehensive medical history to identify prerenal, intrarenal, and postrenal causes.Prerenal causes, such as dehydration, hypotension, or blood loss, should...
36