图森达宁通过减少通过mTOR介导的内质网膜应激引起的肺血管屏障功能障碍来缓解急性肺损伤
Xiaocheng Mao1, Cheng Wang2, Hong Tang1
1Department of Blood Transfusion, Key Laboratory of Jiangxi Province for Transfusion Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, PR China.
概括
图森达宁 (TSN) 通过向mTOR途径,有效治疗急性肺损伤 (ALI),减少炎症,内分泌网膜应激和亡. 这项研究突出了TSN的特点.
科学领域:
- 药理学 药理学是指药理学的学科.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 急性肺损伤 (ALI) 和急性呼吸困难综合征 (ARDS) 是具有有限治疗选择的危急疾病.
- 一种三基的托森丹宁 (TSN) 具有抗炎性质,但其在ALI中的有效性尚不清楚.
研究的目的:
- 调查TSN对ALI的保护作用,并阐明其潜在的分子机制.
- 在ALI模型中评估TSN对内皮通透性,氧化应激和亡的影响.
主要方法:
- 已确定的脂聚糖 (LPS) 诱导的ALI模型在体外和体内.
- 评估了内皮通透性,活性氧物种 (ROS),亡和细胞活力.
- 利用网络药理学和表面等离子体共振 (SPR) 来识别和验证TSN的分子标,专注于mTOR.
- 通过qRT-PCR和西式涂抹量化基因和蛋白质表达.
主要成果:
- TSN显著降低了内皮通透性和ALI严重程度.
- TSN减轻了ROS的产生,脂质过氧化,内质网膜 (ER) 应激和亡.
- 网络药理学和SPR将mTOR确定为一个关键目标,TSN抑制mTOR信号传递. mTOR激活器MHY1485扭转了TSN的保护作用.
- 在体内,TSN和拉巴胺显示出对ALI的协同保护作用.
结论:
- 通过向mTOR通路,TSN显示出对ALI的显著保护作用.
- 通过调节ER压力,细胞亡和内皮损伤,TSN可以减轻ALI.
- 这些发现表明TSN是ALI的有前途的治疗剂,具有潜在的临床应用.
相关概念视频
01:22PI3K/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
01:18Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
135
Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
135
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
386
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
386
03:03mTOR Signaling and Cancer Progression
3.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.7K