朱阿可通过激活AKT/NRF2/HO-1通路来缓解肝缺血-再输液损伤
Haoran Fang1, Min Xu1, Jiakai Zhang1
1Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Biochimica et biophysica acta. Molecular basis of disease
|September 5, 2024
概括
朱胺A (JuA) 通过减少氧化应激,炎症和亡来保护肝脏缺血-再输液 (I/R) 损伤. 这种天然化合物激活AKT/NRF2/HO-1通路,为肝损伤提供了潜在的治疗策略.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 肝缺血-再输血 (I/R) 损伤是一个重大的临床挑战,治疗选择有限.
- 朱化A (JuA) 是一种天然化合物,具有已知的抗氧化,抗炎和抗丧性质.
- 朱阿在肝脏I/R损伤中的保护作用以前没有被研究过.
研究的目的:
- 为了研究Jujuboside A (JuA) 对肝脏缺血-再输液 (I/R) 损伤的保护作用.
- 阐明JuA在减轻肝脏I/R损伤中的作用的潜在分子机制.
主要方法:
- 建立用于肝脏I/R的小鼠模型和用于低氧/低氧化 (H/R) 的AML12细胞模型.
- 使用组织学分析,肝酶测定 (ALT,AST) 和细胞活力测试来评估肝损伤.
- 通过各种生物化学和显微镜技术评估氧化应激,炎症,亡和线粒体损伤.
- 使用分子对接和西部斑分析探索分子通路,包括对AKT/NRF2/HO-1信号通路的调查.
主要成果:
- 在I/R模型中,JuA预治疗显著降低了肝硬化,并使ALT和AST水平升高正常化.
- 在H/R模型中,JuA增强了细胞活力,并抑制了氧化应激,炎症和NLRP3炎症酶激活.
- JuA预治疗缓解了线粒体损伤和亡,显示出广泛的保护作用.
- 机理学研究表明,JuA激活了AKT/NRF2/HO-1信号通路,而AKT抑制部分逆转了其保护作用.
结论:
- 朱胺A (JuA) 有效地减轻肝脏缺血-再输液 (I/R) 损伤.
- JuA通过抑制氧化应激,炎症,亡和线粒体损伤来发挥其肝保护作用.
- AKT/NRF2/HO-1信号通路对于JuA在肝脏I/R损伤中的治疗作用至关重要.
相关概念视频
Liver Regeneration
3.2K
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
3.2K
Liver Physiology
456
The liver, an essential organ in the human body, performs over 200 vital functions that can be broadly categorized into metabolic, hematological, endocrine regulation, and bile production.
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of 70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can...
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of 70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can...
456
Nitric Oxide Signaling Pathway
5.0K
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
5.0K
NF-κB-dependent Signaling Pathway
7.4K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.4K
Ischemic Heart Disease: Overview
1.2K
Ischemic heart disease occurs when the heart's blood supply dwindles, causing an ominous lack of oxygen and nutrients. This deficiency, stemming from reduced or obstructed blood flow, spells danger, leading to heart muscle damage and dysfunction.
Atherosclerosis, the primary malefactor, orchestrates this dangerous condition. It manifests as the accumulation of fatty deposits, akin to insidious plaques, within arterial walls. As time elapses, these plaques metamorphose, hardening and...
Atherosclerosis, the primary malefactor, orchestrates this dangerous condition. It manifests as the accumulation of fatty deposits, akin to insidious plaques, within arterial walls. As time elapses, these plaques metamorphose, hardening and...
1.2K
PI3K/mTOR/AKT Signaling Pathway
3.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.4K


