秋水仙碱、心血管疾病的炎症和纤维化:合并三个经典故事

G. Chaldakov
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引用次数: 4

摘要

秋水仙碱,从秋水仙中分离出来,是一种治疗急性痛风性关节炎的药物,几千年来一直沿用至今。在过去的几十年里,这种非常古老的药物的使用已经超出了痛风治疗的范围。这是由于以下知识的进步:(1)高尿酸血症和痛风与心血管疾病的关联,(2)细胞骨架微管(ÐœÐⅱ),以及(3)秋水仙碱的抗炎和抗纤维化作用,秋水仙碱是一种经典的mt分解剂(抗微管蛋白)。在这里,我们介绍了保加利亚在20世纪70年代初在保加利亚瓦尔纳医学研究所电子显微镜实验室研究血管平滑肌细胞的分泌(纤维生成)功能时对秋水秋碱治疗心血管疾病的潜力的贡献。从那时起,低剂量秋水秋碱(LoDoCo, 0.5 - 1.0 mg/d)越来越多地被口服用于心血管疾病的治疗,如急性冠状动脉综合征、心脏手术后心房颤动、心包炎、心脏肥厚相关性心力衰竭和系统性坏死性血管炎。因此,秋水仙碱可能成为目前治疗这些疾病的新工具。这只是一个mt分解药物的例子。在对这种抗微管蛋白疗法获得真正的信心之前,肯定需要进一步的研究。这可能导致开发新的和更特异的抗微管蛋白治疗心血管疾病。Biomed Rev 2017;28日:105 - 110。关键词:微管,微管蛋白,秋水仙碱,抗微管蛋白,心血管疾病,炎症,纤维化
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Colchicine, Inflammation and Fibrosis in Cardiovascular Disease: Merging Three Classical Tales
Colchicine, isolated from Colchicum autumnale, is a drug for acute gouty arthritis known from thousands of years whose use has survived to modernity. Over the past decades, the use for this very old drug extended beyond gout therapy. This was due to the advance in knowledge of (i) association of hyperuricemia and gout with cardiovascular disease, (ii) cytoskeletal microtubules (МТ), and (iii) anti-inflammatory and antifibrotic effects of colchicine, a classical MT-disassembling agent (antitubulin). Here, we present the Bulgarian contribution to colchicine potential in the therapy of cardiovascular disease that has emerged in the early 1970`s in the Laboratory of Electron Microscopy, Medical Institute, Varna, Bulgaria, studying the secretory (fibrogenic) function of vascular smooth muscle cells. From this time onward, low-dose colchicine (LoDoCo, 0.5 - 1.0 mg/daily) was increasingly administered orally for therapy of cardiovascular disease such as acute coronary syndromes, cardiac surgery postoperative atrial fibrillation, pericarditis, cardiac hypertrophy-associated heart failure, and systemic necrotizing vasculitis. Thus colchicine might be a new tool in the present therapeutic armamentarium for these diseases. It is simply an example of MT-disassembling drugs. Further studies will definitely be required before gaining real confidence in this kind of antitubulin therapy. This may lead to developing new and more specific antitubulins for therapy of cardiovascular disease. Biomed Rev 2017; 28: 105-110. Keywords: microtubules, tubulin, colchicine, antitubulins, cardiovascular diseases, inflammation, fibrosis
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