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Rosiglitazone

内分泌

关键词内分泌 治疗药物 糖尿病

词汇介绍

拓展阅读

解析

Rosiglitazone

释    义   n. 罗格列酮;梵帝雅

例    句   But they say that despite these limitations, patients and providers should consider the potential for serious adverse cardiac effects of treatment with rosiglitazone.但他们说,尽管有这些限制,病人和供者应考虑到用罗格列酮治疗中潜在的严重不良的心脏治疗。

概述

罗格列酮是一种抗糖尿病药物的噻唑烷二酮类,通过与脂肪细胞中的PPAR结合并使细胞对胰岛素更敏感,它可以作为胰岛素增敏剂。临床应用罗格列酮于1999年获得美国FDA批准,并于2000年获得EMA批准。然而,EMA要求进行两项长期不良影响的上市后研究,一项针对慢性心力衰竭,另一项针对心血管疾病。该药物被批准用于2型糖尿病患者的血糖控制,这是通过糖基化血红蛋白A1c(HbA1c)作为替代终点来进行的,与其他口服降糖药相似。关于不良反应的争议已大大减少了罗格列酮的使用。已发表的研究没有提供证据表明罗

Anti-Diabetic Countermeasures Against Tobacco Smoke-Dependent Cerebrovascular Toxicity: Use and Effect of Rosiglitazone复制标题

抗烟草烟雾依赖性脑血管毒性的糖尿病对策: 罗格列酮的使用及效果

发表时间:2019-08-29

影响因子:4.2

作者: Sivandzade F

期刊:Int J Mol Sci

A vast number of deaths worldwide, are attributed to smoking, as a consequence of its effects on the vascular system in the body. As a major component of the vascular system, the endothelial cells are significantly impaired as a result of exposure to the toxic chemicals, free radicals, aromatic compounds and nicotine contained within tobacco smoke (TS). Endothelial function is critical to maintain the integrity, homeostasis and detoxifying role of the blood–brain barrier (BBB). The exact components of cigarette smoke and the mechanism of the pathophysiological link between smoking and vascular injury are not fully specified. The mechanism of vascular damage induced by cigarette smoking is multifaceted; dysfunction of the BBB through activation of oxidative, inflammatory and immune responses leads to pathogenesis and progression of cerebrovascular and neurodegenerative disorders, including stroke, Alzheimer’s disease (AD), Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), depression, vascular dementia and Huntington’s disease (HD). In fact, the selectivity of the BBB, a dynamic and complex interface between the blood and the central nervous system (CNS), allows some nutrients to transport between the peripheral circulation and the brain, while it prevents many toxic compounds and pathogens from entering the brain. There is now a wealth of evidence suggesting the major role of oxidative stress in endothelial dysfunction in the cerebrovascular level. Despite the valid evidence for the significant link between cigarette smoking and vascular impairment, the impact of TS exposure on the BBB has not been completely addressed. In the recent work of our group, the involvement of common pathogenic modulators of BBB impairment was confirmed so that chronic cigarette smoking and hyperglycemia (HG) carried similar risks for cerebrovascular diseases and stroke, sharing similar pathogenic mechanisms. This result accounts for the reason for the possible application of anti-diabetic drugs to prevent/reduce BBB damage promoted by the chronic TS exposure. Rosiglitazone (RSG) is a member of the thiazolidinedione family of antidiabetic agents that can improve insulin sensitivity through modulating adiponectin gene expression in muscle and adipose tissue, and inhibits hepatic gluconeogenesis. RSG is also considered as a potent and selective transcription factor peroxisome proliferator-activated receptor (PPARγ) agonist which is a nuclear receptor that regulates numerous genes implicated in glucose homeostasis, and fatty acid metabolism. In humans, PPAR receptors are found in key target tissues for insulin action, such as adipose tissue, skeletal muscle, and liver. Despite the unknown mechanism of RSG, numerous studies and our previous work has confirmed the protective effect of RSG against oxidative damage. The aim of the present study is to validate and assess the previous results using animal models in vivo and to confirm RSG’s role in the activation of counteractive antioxidative mechanisms to reduce TS toxicity at the BBB.

译文

由于吸烟对人体血管系统的影响,全世界有大量的人死于吸烟。作为血管系统的主要成分,由于暴露于烟草烟雾(TS)中的有毒化学品、自由基、芳香族化合物和尼古丁,内皮细胞显著受损。内皮功能是维持血脑屏障(BBB)的完整性、稳态和解毒作用的关键。吸烟的确切成分和吸烟与血管损伤的病理生理联系机制尚未完全阐明。吸烟引起血管损伤的机制是多方面的,BBB通过氧化、炎症和免疫反应的激活导致脑血管和神经退行性疾病的发病和发展,包括脑卒中、阿尔茨海默病(AD)、帕金森病(PD)、肌萎缩侧索。硬化症(als)、抑郁症、血管性痴呆和亨廷顿病(hd)。事实上,血液和中枢神经系统(CNS)之间的动态和复杂界面的BBB的选择性,允许一些营养物质在外周循环和大脑之间输送,同时它阻止许多有毒化合物和病原体进入大脑。现在有大量的证据表明氧化应激在脑血管内皮功能障碍中的主要作用。尽管有有效证据表明吸烟与血管损伤之间存在显著联系,但TS暴露对血脑屏障的影响尚未完全解决。在本组近期的工作中,我们证实了bbb损伤的常见致病性调节剂的参与,使得慢性吸烟和高血糖(hg)对脑血管疾病和中风具有相似的风险,具有相似的致病机制。这一结果解释了应用抗糖尿病药物预防/减轻慢性ts暴露引起的bbb损伤的可能性。罗格列酮(rosiglitazone,rsg)是噻唑烷二酮类降糖药家族的一员,通过调节肌肉和脂肪组织脂联素基因表达,提高胰岛素敏感性,抑制肝脏糖异生。RSG也被认为是一种强效和选择性的转录因子过氧化物酶体增殖物激活受体(PPARγ)激动剂,它是调节葡萄糖稳态和脂肪酸代谢的众多基因的核受体。在人类中,PPAR受体在胰岛素作用的关键靶组织中发现,例如脂肪组织、骨骼肌和肝脏。尽管RSG的机制未知,但大量的研究和我们以前的研究证实了RSG对氧化损伤的保护作用。本研究的目的是验证和评估以前的结果,使用动物模型在体内,并确认RSG的作用,在激活反作用的抗氧化机制,以减少TS毒性在BBB。