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糖尿病的心血管并发症:动物模型的启示。

Cardiovascular complications in diabetes: lessons from animal models.

机构信息

Department of Biomedical Sciences and Human Oncology, Pharmacology Section, University of Bari, Bari, Italy.

出版信息

Curr Med Chem. 2011;18(12):1806-19. doi: 10.2174/092986711795496755.

Abstract

Micro- and macro-vascular complications are the leading causes of morbidity and mortality in type 1 and type 2 diabetic patients. Despite the vast clinical experience linking diabetic metabolic abnormalities to cardiovascular lesions, the molecular basis of individual susceptibility to diabetic cardiovascular injury is still largely unknown. Significant advances in this area may come from studies on suitable animal models. Although no animal model can accurately reproduce the human disease, experimental studies in animals have the great advantage to eliminate factors such as ethnicity, economic and geographic variables, drug interactions, diet, gender and age differences that importantly limit clinical studies. Indeed, appropriate animal models have provided important information on genetic and environmental risks of diabetes, and helped to dissect molecular mechanisms underlying the development, progression and therapeutic control of this disease. Unfortunately, none of the diabetic models presently available fully mimics the human syndrome. Therefore, the current knowledge on the pathogenesis of cardiovascular complications relies on the evaluation of distinct phenotypes from various diabetic models. In addition to strains prone to diabetes, this disease can be induced by surgical, pharmacological or genetic manipulation in several animal species. Rodents are the most used, although some studies are still performed in larger animals as rabbits, cats, pigs or monkeys. Far from being exhaustive, this work should serve as a general overview of the most relevant clues provided by major species and models for the overall comprehension of cardiovascular complications in type 1 and type 2 diabetes.

摘要

微血管和大血管并发症是 1 型和 2 型糖尿病患者发病率和死亡率的主要原因。尽管大量临床经验将糖尿病代谢异常与心血管病变联系起来,但个体易患糖尿病心血管损伤的分子基础仍知之甚少。在这一领域的重大进展可能来自于对合适的动物模型的研究。尽管没有一种动物模型可以准确模拟人类疾病,但动物实验研究具有很大的优势,可以消除种族、经济和地理变量、药物相互作用、饮食、性别和年龄差异等重要限制临床研究的因素。事实上,适当的动物模型为糖尿病的遗传和环境风险提供了重要信息,并有助于剖析这种疾病发展、进展和治疗控制的分子机制。不幸的是,目前现有的糖尿病模型都不能完全模拟人类综合征。因此,目前对心血管并发症发病机制的了解依赖于对各种糖尿病模型不同表型的评估。除了易患糖尿病的品系外,这种疾病还可以通过手术、药理学或遗传操作在几种动物物种中诱导。啮齿动物是最常用的,但一些研究仍在兔子、猫、猪或猴子等较大的动物中进行。这项工作远非详尽无遗,它应该作为主要物种和模型为全面理解 1 型和 2 型糖尿病心血管并发症提供的最相关线索的概述。

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