健康和疾病的发育起源研究现状

Current Opinion in Developmental Origins of Health and Disease

大量流行病学和动物实验研究显示,发育早期不利因素,特别是宫内营养失衡(包括营养不良及营养过剩),导致机体生理和代谢发生永久改变,引发子代肥胖、2型糖尿病、高血压、冠心病等成年慢性疾病的发生发展。这一过程发生在胎儿发育的窗口期,即健康和疾病的发育起源(developmental origins of health and disease,DOHaD)。目前,其具体机制引发了国内外学者的广泛关注,特别是代谢调节关键基因在转录水平的改变及表观遗传学在引发成年代谢表型中的作用。深入了解并进一步探讨其机制以寻求有效的干预方式对控制心血管疾病及2型糖尿病的流行意义重大,对于经济快速转型的发展中国家更是意义深远。

Environmental factors during early life in development have been shown to influence the susceptibility to develop diseases in later life.In particular,there is a wealth of evidence from both epidemiological and animal studies for greater effect on an offspring＇s risk of developing adult chronic diseases（including hypertension,diabetes,coronary artery disease,obesity,et al） as a result of unbalanced maternal nutrition,ranging from poor to rich environments.These findings indicate new bridges of causality,inferring the possibility of early establishment of persistent metabolic and physiological adjustments that determine morbid outcomes throughout life,grouped as the developmental origins of health and disease（DOHaD）.The mechanisms by which nutritional insults during a period of developmental plasticity result in adult metabolic phenotype are now beginning to receive considerable scientific interest,in particular the epigenetic and transcriptional regulation of key metabolic genes in response to nutritional stimuli that mediate persistent changes and an adult metabolic phenotype,a continued and greater understanding of these mechanisms will eventually allow specific interventions,with a favorable impact on the global incidence of cardiovascular disease and type 2 diabetes in the future.