瘦素与高血压相关性研究进展

Current Understanding of the Correlation of Leptin and Hypertension

瘦素是一种由肥胖基因编码,主要由脂肪细胞合成分泌的肽类激素。研究表明,瘦素与高血压的发生发展相关,其机制可能是:瘦素对血管有舒张或收缩双向调节作用,该作用呈剂量、时间依赖性。在慢性高瘦素血症状态下,由于血管内皮功能障碍使瘦素诱导的一氧化氮合成减少,交感神经活性增加,交感神经的收缩血管效应占优势,导致血压升高。瘦素可以通过中枢或外周机制激活交感神经系统,前者包括激活POMC-MC3/4R通路和肾素-血管紧张素系统,后者可能与瘦素促进外周交感神经轴索生长有关。此外,在慢性高瘦素血症状态下,瘦素的局部促尿钠排泄作用被破坏,表现为对水钠的重吸收增加而导致水钠潴留,从而参与高血压的发生发展。瘦素与瘦素受体基因多态性与非肥胖相关高血压的发生有一定相关性。

Leptin,encoded by the obese gene,is a kind of peptide-hormone produced mainly by adipose tissue.Many studies have provided evidence that leptin is related to hypertension.The mechanism bases on the fact that leptin can both constrict and dilate the blood vessels.The regulation of vascular activity by leptin is both dose-dependent and time-dependent.Under chronic hyperleptinaemia condition,the NO-mediated vasodilatory effect of leptin is impaired owing to vascular endothelium dysfunction and the stimulation of the sympathetic nerve system（SNS）by this hormone is unop-posed.Thus,the effect of SNS on vascular activity takes the dominant place,which lead to the constriction of blood ves-sels,increasing the blood pressure consequently.Leptin activates SNS through central nerve system（CNS）or peripheral mechanisms.In CNS,leptin activates SNS by POMC-MC3/4R pathway and renin-angiotensin system while in peripheral tissue,leptin stimulates the axonal growth of sympathetic nerve.In addition,under chronic hyperleptinaemia condition, the local natriuretic effect of leptin is impaired,which lead to the increased reabsorption of sodium and water and ac-counts for the development of hypertension partly.Both leptin gene and leptin receptor gene polymorphisms may contrib-ute to hypertension independent of obesity.