阿利,肺动脉高血压的新兴治疗方法:一项实验性研究
José L Sánchez-Gloria1, Constanza E Martínez-Olivares2, Leonardo Del Valle-Mondragón3
1Department of Internal Medicine, Division of Nephrology, Rush University Medical Center, Chicago, IL 60612, USA.
International journal of molecular sciences
|August 26, 2023
概括
在大中发现的一种化合物素,通过减少血管重塑和改善内皮功能来治疗肺动脉高血压 (PAH) 是有前途的. 这项研究表明,氨酸可能是PAH的潜在治疗选择,可以提高生存率.
科学领域:
- 心血管研究研究心血管研究
- 药理学 药理学是指药理学的学科.
- 氧化压力研究研究 氧化压力研究
背景情况:
- 肺动脉高血压 (PAH) 是一种严重的疾病,其特点是血管重塑,内皮功能障碍和氧化应激.
- 目前对PAH的治疗有局限性,需要探索新型治疗剂.
研究的目的:
- 研究以其抗高血压和抗氧化特性而闻名的素在改善实验性PAH方面的潜力.
- 在PAH的小鼠模型中评估艾利对血管改造,内皮功能和氧化应激的影响.
主要方法:
- 在使用单克罗他林 (60毫克/公斤) 的老鼠中诱导了肺动脉高血压.
- 艾利 (16 mg/kg) 给了患有PAH的老鼠.
- 测量了关键的生理参数,包括体重,生存率,中间壁厚度,右心室缩,以及各种信号分子 (血管新生素II,氧化,四水生物,循环瓜诺辛单酸盐,Ang-(1-7) 的度.
- 分析了血管素转化酶II,血管素II类型1受体,Nrf2,HIF-1α和VEGF的基因表达水平.
主要成果:
- 阿利辛的使用改善了PAH大鼠的体重增加和生存率.
- 阿利预防了中间壁厚度和右心室缩,表明血管重塑减少.
- 氨酸调节了氨酸 - ангиотензин系统 (RAS) 并增强了依赖氧化 (NO) 的血管扩张.
- 氧化应激通过增加Nrf2表达和预防HIF-1α和VEGF过度表达而得到改善.
结论:
- 阿利有效地减弱了实验性PAH中的血管重塑和右心室缩.
- 氨酸的治疗作用归因于其改善NO依赖血管扩张,调节RAS和减少氧化应激的能力.
- 阿利辛显示出作为PAH的替代或辅助疗法的潜力,改善内皮功能和生存率,特别是在治疗失败或不耐受的情况下.
相关概念视频
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
215
Prostacyclin receptor agonists are a class of therapeutic agents integral to managing pulmonary arterial hypertension (PAH). These drugs operate by mimicking the action of prostaglandin I2, or PGI2, a naturally occurring compound in the body.
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
215
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
203
Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
203
Treatment for Pulmonary Arterial Hypertension: Oxygen Therapy for Respiratory Failure
263
Oxygen therapy has emerged as a significant tool in enhancing the quality of life for patients suffering from pulmonary arterial hypertension (PAH). While this therapy has principally been studied on patients with significant hypoxemia, this therapeutic approach helps prevent potential organ damage and can be administered in the comfort of one's home.
Oxygen therapy is vital in increasing and maintaining blood oxygen levels in PAH patients. As a result, it aids in reducing fatigue,...
Oxygen therapy is vital in increasing and maintaining blood oxygen levels in PAH patients. As a result, it aids in reducing fatigue,...
263
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
201
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...
201
Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors
187
Phosphodiesterase 5 (PDE5) inhibitors are potent enzymes that function to hydrolyze cyclic nucleotides to their corresponding 5' monophosphates. Their unique biochemical properties have been applied in treating Pulmonary Arterial Hypertension (PAH).
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
187


