瘦素对内皮功能的影响及在原发高血压中的变化  

Direct effect of leptin on endothelial function and their changes in patients with essential hypertension

作　　者：姚艳[1] 吴格如[1] 田红燕[1] 杨岚[1] 

机构地区：[1]西安交通大学医学院第一附属医院心内科,陕西西安710061

出　　处：《第四军医大学学报》2009年第24期3132-3135,共4页Journal of the Fourth Military Medical University

摘　　要：目的:观察原发性高血压(EH)患者血清瘦素(lep-tin)和内皮功能的改变、leptin对内皮功能的直接影响及其可能信号转导通路.方法:观察64例EH患者和性别、年龄相匹配的60例正常对照人群血清leptin、内皮素-1(ET-1)及一氧化氮(NO)水平的变化.并采用细胞培养技术观察:leptin对人脐静脉内皮细胞株合成和分泌NO和ET-1的直接影响;酪氨酸激酶抑制剂genestein及磷脂酰肌醇-3激酶(PI3-激酶)抑制剂wortmannin对此作用的影响.结果:与正常血压对照组相比,EH患者血清leptin,ET-1及ET-1/NO均增高(P均<0.05);血清leptin水平与ET-1和收缩压呈显著正相关关系;高浓度leptin可直接促进人脐静脉内皮细胞NO的合成和分泌而对ET-1的合成无明显影响;genestein及wortmannin可抑制leptin的促NO效应.结论:EH患者常合并leptin抵抗及内皮功能失调;酪氨酸激酶和PI3-激酶可能是实现leptin促NO合成效应的两种信号转导效应分子.AIM：To observe serum leptin changes in patients with essential hypertension and direct effect of leptin on endothelial function and its possible signaling pathways.METHODS：Sixty-four patients with essential hypertension（EH） and 60 normotensive subjects matched for age and sex were involved to observe the change of serum leptin,endothelin-1（ET-1） and nitric oxide（NO）.Cell culture technique was used to observe the direct effect of leptin on NO and ET-1 prodution from human umbilical vein endothelial cells（HUVEC）.Tyrosine kinase inhibitor（genestein） and phosphatidylinositol 3-kinase（PI 3-kinase） inhibitor（wortmannin） were added to confer the possible signaling pathway of above effect.RESULTS：EH patients had high serum leptin[（7.95±4.01） μg/L vs （5.68±4.56） μg/L,P0.05],ET-1[（104.24±34.18） ng/L vs （58.26±11.0） ng/L,P0.001] and ET-1/NO[（2.12±1.46） vs （1.24±1.21）,P0.05];Serum leptin level was significantly positively correlated with serum ET-1（r=0.427,P0.05） and systolic blood pressure（r=0.312,P0.05）;High concentration of leptin（1,10 mg/L） had direct effects of promoting the NO secretion from HUVECs;no matter high or low concentration of leptin have no influence on ET-1 synthesis from HUVECs;The effect of leptin on NO was blocked by either tyrosine kinase inhibitor-genestein or PI 3-kinase inhibitor-wortmannin.CONCLUSION：EH patients had leptin resistance and endothelial dysfunction;Both tyrosine kinase and PI 3-kinase were the possible post-receptor signal transduction effector molecules of leptin in HUVECs on NO production;Abnormal receptor or post-receptor signaling transduction of leptin may be the pathological causes of both leptin resistance and endothelial dysfunction in EH.

关 键 词：瘦素 原发性高血压 一氧化氮 内皮 

分 类 号：R544.1[医药卫生—心血管疾病]