相关实验视频
Updated: Jul 9, 2026

08:09
A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish
Published on: June 7, 2018
9.7K
阿斯泰米醇通过增强Ptgs2加剧5-甲引发的心脏毒性
Mengshi Xie1, Pan Jiang2,3, Xiyang Yang4
1Department of Cardiology, Zhongshan Hospital Wusong Branch, Fudan University, Shanghai, China.
Cardiovascular toxicology
|January 8, 2025
概括
5-甲 (5-FU) 和阿斯泰米 (AST) 的结合加剧了5-FU诱导的结肠癌心脏毒性,增加了心脏细胞死亡和炎症. 这种药物组合提高了Ptgs2表达,这是与心血管问题相关的标记物.
科学领域:
- 心脏病学 心脏病学
- 在瘤学瘤学.
- 药理学 药理学 是一个学科.
背景情况:
- 5-甲 (5-FU) 是一种具有已知的心血管风险的关键结肠癌药物.
- 抗胺剂阿斯泰米 (AST) 也带有心血管毒性问题.
- 5-FU和AST对结肠癌心脏毒性的联合作用尚不清楚.
研究的目的:
- 在结肠癌治疗期间,调查阿斯泰米 (AST) 在5-甲 (5-FU) 诱导的心脏毒性的作用.
- 阐明5-FU和AST组合的心脏毒性作用背后的机制.
主要方法:
- 建立了5-FU诱导心脏毒性的体外 (HL-1心肌细胞) 和体内 (BALBc小鼠) 模型.
- 评估心脏功能,纤维化,心肌细胞亡,线粒体反应性氧物种 (mtROS) 和巨细胞极化.
- 量化前列腺素-内氧化合成酶2 (Ptgs2) 蛋白质表达使用西方布洛特.
主要成果:
- 在小鼠中,阿斯提米 (AST) 加重了5-甲 (5-FU) 诱导的心脏功能障碍和纤维化.
- AST和5-FU的组合在体外增加了心肌细胞亡和mtROS生成.
- 前炎性M1-样巨细胞占主导地位,Ptgs2表达在组合组中升高.
结论:
- 在结肠癌模型中,AST和5-FU的组合显著增强了心脏毒性.
- 这种增强是通过增加心肌细胞亡,炎症和增加Ptgs2表达的介导.
- 这些发现突出了与这些药物的同时使用相关的潜在心血管风险.
相关概念视频
Teratogenicity
The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
Acid Suppressive Drugs for Peptic Ulcer Disease: Proton Pump Inhibitors
Peptic ulcers, often induced by H. pylori infections or NSAID usage, arise from disruptions in the delicate balance of gastric acid production. Peptic ulcers stem from heightened gastric acid levels due to H. pylori infections or NSAID use. The protective mucus layer diminishes in the presence of these factors, allowing gastric acid to erode the stomach lining and form ulcers.
Gastric acid, a potent cocktail of hydrogen and chloride ions, is produced in specialized parietal cells within the...
Gastric acid, a potent cocktail of hydrogen and chloride ions, is produced in specialized parietal cells within the...
Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists
5-HT3 receptor antagonists, such as dolasetron, granisetron (Kytril), ondansetron (Zofran), and palonosetron (Axoli), are crucial in managing chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea. These drugs selectively block 5-HT3 receptors in the visceral vagal and spinal afferent nerves, chemoreceptor trigger zone, and the vomiting center. They have a rapid onset of action and can be given as a single dose before chemotherapy. Ondansetron and granisetron, in particular,...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Drug Toxicity: Risk factors
Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...
Drug toxicity: Drug–Drug Interaction
Drug–drug interactions can precipitate toxicity through multiple mechanisms. Absorption interactions alter how drugs enter the body, exemplified when ranitidine increases the absorption of basic drugs, while cholestyramine decreases the levels of propranolol. Protein binding interactions occur when drugs share the same binding sites on plasma proteins. Drugs like aspirin and warfarin, when bound in excess, can lead to increased free drug concentrations, enhancing the potential for...

