【作者】 张克巨；

【导师】 李莉；

【作者基本信息】 郑州大学 ， 内科学， 2010， 硕士

【摘要】 背景和目的随着社会经济和科技的发展,人们社会心理、生活方式和饮食习惯改变,原发性高血压(essential hypertension,EH)的患病率呈现逐渐升高的趋势,引起了医学人员的广泛关注,但其确切发病机制仍不十分清楚,目前认为与环境和遗传因素有关。EH可影响心、脑、肾等重要脏器的血流动力学,并能改变其结构和功能。约有23%-48%的EH患者并发左心室肥厚(left ventricular hypertrophy,LVH)。EH引起的LVH使心肌缺血、心力衰竭、心律失常甚至心脏性猝死发生率增高。在EH合并LVH的众多致病因素中,血管紧张素Ⅱ(Angiotensin 11,Ang 11)发挥的重要作用已经比较明确,即肾素-血管紧张素-醛固酮系统(Renin-Angiotensin-Aldosterone System, RAAS)被激活,循环和局部的AngⅡ水平增高,使血压升高,并具有促纤维化和调节生长信息物质水平的作用,参与LVH的形成。近年来,随着晚期糖基化终末产物(advanced glycosylation end products, AGEs)及晚期糖基化终末产物受体(the receptor for advanced glycation endproducts,RAGE)研究的进展,许多相关的研究资料表明,AGEs具有促纤维化作用,AGEs-RAGE系统参与了心血管疾病的发病过程。有实验研究显示：ARB和ACEI可以抑制AGEs在动物体内某些器官和组织上的表达,推测RAAS和AGEs-RAGE系统在致病机制方面可能存在着交叉作用。但目前有关AGEs在EH合并LVH的发病机制中所起的作用尚不清楚,AGEs与AngⅡ在EH及其合并LVH发生发展中可能存在的相互关系国内外亦未见文献报道。本研究通过测定EH患者及正常对照组血清AGEs、血浆AngⅡ含量,探讨AGEs、AngⅡ与EH及EH合并LVH间的关系,进行相关分析,旨在阐明AGEs、AngⅡ在EH及EH合并LVH患者发病过程中的作用和它们之间的相互关系,为EH防治研究提供理论依据。方法记录受试对象血压、心率、身高、体重、左室心肌重量(LVM)、左室重量指数(LVMI)和体表面积(BSA)等。根据2005年修订版《中国高血压防治指南》中规定的高血压诊断标准(SBP≥140mmHg和(或)DBP≥90mmHg)和2007年《ESH/ESC高血压指南》中提出的LVH诊断标准(男LVMI>125g/m2、女LVMI>110g/m2),筛选出EH组患者共85例,其中包括EH不伴LVH组(EHNLVH组)患者52例和EH合并LVH组(EHLVH组)患者33例。又选取健康人组成正常组对照组50例。分别用双抗体夹心酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)及放射免疫法(Radioimmunoassay,RIA)测定受试对象血清AGEs含量及血浆AngⅡ含量。比较组间指标含量的变化差异,进行相关性分析。实验对象排除继发性高血压、糖尿病、严重肝肾脏疾病、脑卒中、妊娠、甲状腺功能亢进症、重度贫血、恶性肿瘤、外周血管疾病、肺心病、肥厚型心肌病、先天性心脏病和心脏瓣膜病等。应用SPSS13.0软件包对测得的数据进行统计学分析。以P<0.05为数据差异有统计学意义。结果1.与正常对照组比较,EHNLVH组和EHLVH血清AGEs、血浆AngⅡ含量均增高(P<0.05),EH-LVH组患者含量显著增高(P<0.01)2.相关性分析显示；EH组患者AGEs含量与AngⅡ含量呈正相关(r=0.627,P<0.01)；LVMI值与AGEs含量呈正相关(r=0.471,P<0.01),LVMI值与AngⅡ含量呈正相关(r=0.516,P<0.01)3.回归分析显示：AGEs和AngⅡ进入以LVMI为因变量建立的回归方程,它们是EH及EH合并LVH发病的危险因素。结论AGEs和AngⅡ参与了EH及EH合并LVH的发生发展,AGEs和AngⅡ在EH及EH合并LVH的发病机制中存在着协同作用的关系。更多还原

【Abstract】 Backgrounds and ObjectivesThe hypertension shows a gradual increase trend in the incidence with the development of sociometric and technological level,as well as change of social psychology, life style and food habits.Though a number of people pay extensive attention on it, the pathogenesis of EH is not clear yet.Majority think the pathogenesis involves interaction of environment and genetic factors.EH can affect hemodynamics major organs such as heart, brain, kidney, et al,and change its structure and function.There are about 23%-48% of the EH patients who complicate with left ventricular hypertrophy. The incidence rate of myocardial ischemia, heart failure, arrhythmia even Sudden Cardiac Death is higher than normal when LVH existence caused by EH.As one of pathogenic factors in the EH combined LVH, the important role of angiotensinⅡhas been confirmed.With Renin-Angiotensin-Aldosterone System (RAAS) was activating, AngⅡin circulation and tissue are increased while elevating blood pressure, promoting fibrosis and regulate the level of information material indirectly.Recently, data indicate that advanced glycosylation end products (AGEs) and the receptor for advanced glycosylation end products (RAGE) system was involved in the formation. The development of cardiovascular disease with the progress of the study about AGEs and RAGE.AGEs take part in the development of angiocardipathy with the reason of promoting fibrosis. Some of the studies have shown that the AGEs expression can be inhibited by ARB and ACEI of certain organs and tissues in animals, so speculated that there is cross-talk between RAAS and AGEs-RAGE system in the nosogenesis. However, the pathogenesis of AGEs in the EH complicated LVH is indistinct, the possible relationship between AGEs and AngⅡin the development of EH and EH complicated LVH has not been reported currently.This study discuss the possible relationship and correlation of serum AGEs and plasma Ang II of object by measuring their level in the patients with EH and EH combined LVH. Try to find the relationship between AGEs and AngⅡand their role of the pathogenesis of EH and EH complicated LVH,in order to provide a theoretical basis for prevention and treatment research.MethodsThe blood pressure, heart rate, height, weight, left ventricular mass (LVM),left ventricular mass index (LVMI),and body surface area (BSA) of subjects were recorded.According to the diagnostic criteria of blood pressure (SBP≥140mmHg and (or) DBP≥90mmHg) from 2005 revised edition China hypertension guidelines, and the diagnostic criteria (LVMI values, male>125g/m2,female>110g/m2) from 2007 ESH/ESC hypertension guidelines, seek out the EH group(85 cases),including the EH not complicated LVH(EHNLVH group)(52 cases) and EH complicated LVH (EHLVH group)(33 cases).Then set control group from normal people (50 cases). The content of Serum AGEs and plasma AngⅡwere measured respectively by double antibody sandwich enzyme immunoassay (ELISA) method and radioimmunoassay (RIA) method.Then compare the differences of indicators between the two groups to analyze their correlation.Exclude the diseases from object secondary hypertension, diabetes, renal damage, severe liver kidney disease, apoplexy, hyperthyroidism, severe anemia, malignant tumor, peripheral vascular diseases,cor pulmonale, hypertrophic cardiomyopathy, congenital heart disease, valvular heart diseases, and pregnancy, etc.Applicating SPSS13.0 for the measured data results were analyzed statistically, The significant difference is P<0.05 for the data.Results1.Comparing with normal group, level of the serum AGEs and plasma AngⅡin EHNLVH group and EHLVH group are both higher (P<0.05),while EHLVH group increased more significantly (P<0.01).2.It was showed by Correlation analysis that the content of AGEs and AngⅡin patients with EH was positively correlated (r=0.627 P<0.01);LVMI value and the content of AGEs (r=0.471 P<0.01)were positively correlated;as well as the AngⅡ(r =0.516 P<0.01).3.Regression analysis shows that AGEs and AngⅡare both the risk factors for the pathogenesis of LVH.ConclusionAGEs and AngⅡare both take part in the mechanism of the occurrence and development of EH and LVH. It do have interaction relationships between RAAS and AGEs-RAGE system in pathogenesis of EH and EH complicated LVH.更多还原