【作者】 方慧娟；

【导师】 胡健；

【作者基本信息】 中国医科大学 ， 内科学， 2004， 硕士

【摘要】 前言 原发性高血压(EH)是常见的心血管疾病，由于内皮素(ET)在高血压的发病机制中具有重要的病理生理学意义，近年来内皮素水平越来越引起人们的关注。ET是1988年日本学者Yanagisawa首先从猪的主动脉内皮细胞(EC)培养液中分离的。既往，对单纯高血压的病人或合并糖尿病的病人内皮素研究的比较多，但是对高血压合并糖耐量减低(IGT)病人的ET的研究较少，本文通过对单纯高血压的病人、高血压合并IGT的病人、高血压合并糖尿病的病人及健康人分别测定血浆ET、胰岛素(INS)、血糖数值，初步探讨高血压合并IGT的病人与血糖、胰岛素抵抗(IR)、体重指数(BMI)等因素的相关性及其临床意义。 实验对象 1．实验对象与分组 (1)对照组：2003年5月-2003年12月随机选择42例健康人，平均年龄59.31±10.24岁，均无高血压，糖尿病等疾病症状，并经过体检及实验室检查均正常的健康人。 (2)单纯高血压组(A组)：来自2003年5月～2003年12月中国医科大学附属第一临床医院内科的病人，43例，平均年龄61.06±9.20岁。入选标准为符合1999年10月颁布的《中国高血压防治指南》的高血压诊断标准，并且空腹血糖(FPG)＜6.0 mmol／L，口服葡萄糖耐量试验(OGTT)的服糖后2小时血糖(2HPG)＜7.8 mmol／L的病人。 (3)高血压伴IGT组(B组)：选自中国医科大学附属第一临床医院内科的病人，77例，平均年龄59.36±11.66岁。入选标准为符合1999年10月颁布的《中国高血压防治指南》的高血压诊断标准，并且OGTT的2HPG在7.8mmol／L～11.1mmol／L之间的病人。 (4)高血压伴糖尿病(C组)：选自中国医科大学附属第一临床医院内科病人，共38例，平均年龄61.26±9.39岁，入选标准为符合1999年10月颁布的《中国高血压防治指南》的高血压诊断标准，并且有糖尿病史且经过OGTT证实FPG〕7 .0~。FL，或OGTT的ZHPG〕11 .1~。FL。实验方法 1.对所有研究对象记录姓名、年龄、性别，按统一方法测血压、、身高、体重、腰围、臀围，均于禁食12小时后晨起空腹采肘静脉血。 2.血浆内皮素的测定:取全血2而，注人含有抗凝剂EDTA30、il和抑肤酶400IU的试管中混匀，离心分离血浆，吸取上层血浆置一70℃冰箱内。 3.同时抽静脉血2血，注人试管中自然凝固后，分离血清一70℃保存。 4.测定血糖:分别测FPG及ZHPG，测定用氧化酶法。 5.计算体重指数( BMI)，腰臀比(WHR):BMI二体重(kg)/身高(mZ)，wHR=腰围/臀围。 6.胰岛素抵抗指数(IR):选用稳态模型评价胰岛素抵抗程度HOMA-IR=FINs x FPG/22.5。 7.统计学分析 用SPSS ro.o软件进行统计学分析，所有数值以均数，标准差(又士s)表示，显著检验采用t检验，用Pearson直线相关性分析法。P<0，05为统计学上差异有显著性。实验结果 1.高血压病人巧8例和对照组42例，在年龄、性别上无显著差别(P>0.05)。与对照组比较，高血压病人的收缩压(SBP)、舒张压(DBp)、BMI、腰臀比(WHR)和腰围有显著性差别(P<0 .05)。 2.A组、B组、C组与对照组比较的血浆ET、HOMA一IR、空腹胰岛素(FINS)参数均明显高于对照组具有显著性差异，ET以C组(190.44士34·76ng/L)最大，其次为B组(143 .21，11·30n扩L)，再次为A组(97·97士9·13n岁L)，它们与对照组(67.53士n.10n扩L)比较差异有显著性意义(P<0.01)，A组与B组间有显著差异(P<0.05)，B组与C组比较差异有显著性意义(p<0.05);HOMA一IR以A组(10.65士2.81)最大，其次为B组(5.50*0.63)，再次为A组(3.52士0.44)，它们与对照组(2.41土0.31)比较差异有显著性意义(P<0.01)，A组与B组间有显著差异(P<0.05)，B组与C组有显著差异(P<0.05)。 3.分析表明高血压伴IGT病人的血浆内皮素与年龄、BMI、腰围、臀围，FPG、ZHPG、空腹胰岛素(FINS)、HOMA一IR、SBP、DBP呈正相关。。讨论 EH是常见的心血管疾病，1988年Yanagasawa等提出ET生成的增加参与了高血压的发病过程，并且ET在高血压的发病机制中具有重要的病理生理学意义。ET对动脉有强烈收缩作用，并且有剂量—效应关系，使肌体保持适宜的血管紧张度。血压的稳定有赖于血管内皮功能的完整，血管内皮受损，与EH互为因果。原发性高血压患者内皮源性舒张因子水平下降，同时ET升高。ET的血管活性效应还影响内皮细胞的增殖，进一步损伤血管内皮并导致其它细胞增殖和促细胞分裂因子的释放。因此，ET水平升高是血管内皮细胞受损的敏感指标之一。 本研究结果表明高血压病人ET值与对照组相比较明显升高，与文献报道的相一致。近年研究表明，ET参与血压的平衡调节，血管内皮细胞损伤、再生，产生大量的ET，而引起EH的相应临床和病理改变。在原发高血压病人和多种实验性高血压动物均发现血浆ET水平明显升高，而且血压越高，血浆ET浓度越高。表明高血压时血浆ET的合成与释放是增加的。最近得到高血压时血管内皮细胞生成ET增加更直接证据。高血压患者不但存在内皮细胞结构和功能变化，而且高血压状态又进一步加重血管内皮细胞结构和功能的损伤，形成?更多还原

【Abstract】 Essential hypertension ( EH) is one of the commonest cardiovascular diseases. Because endothelin (ET) plays a vital role in the mechanism of EH, meas-ureing ET is paid more attention. ET that was firstly found by Japanese scholar Yanagisawa in 1988 is a vascular contractor. ET has strong vasocontriction and promotes the proliferation of vasocular smooth muscles. In the past there were many ET studies about hypertensive patients and diabetes mellitus, but there were few ET studies of hypertensive patients with impaired glucose tolerance (IGT). This study will observe ET, insulin, blood glucose(BG) , body mass index(BMI) , waist circumference, hip circumference of hypertensive patients with normal glucose tolerance (NGT) , IGT , diabetes mellitus (DM) or heathy person. The study will inquired into the correlating relationship of ET, BG, insulin resistance(IR) , BMI, blood pressure(BP)and their clinical significances in hypertensive patients with IGT.Materials1. Sample:(1) control group: 42 healthy persons(22 men and 20 women, mean 59.31 ± 10. 24 years old ) were taken as control.(2) Group A : 43 hypertensive patients (24 men and 19 women, mean 61. 06 ±9.20years old) who were admitted to the first affiliated hospital of china medical university between May 2003 and December 2003 were taken as group A. They conformed to the diagnosis of hypertension, which was issued in October 1999. They also had 2HPG < 7. 8mmol/L(3) group B: 77 hypertensive patients(47 men and 30 women, mean 59.36 ± 11.66 years old ) admitted to first affiliated hospital of china medical university were taken as group B, which had 2HPG 7. 8mmol/L - 11.2mmol/L. (4) group C : 38 hypertensive patients (22 men and 16 women, mean 61.26 ±9.39 years) were taken as group C, which had FPG > 7.0mmol/L or 2HPG>11.lmmol/L.Methods1. All subjects were recorded their names, age and measured their BP, body weight, height, waist circumference and hip circumference, respectively. A sample of venous blood were drawn at early morning before breakfast to measure the ET, FINS and FPG.2. Determination of ET ; Blood samples were drawn in plastic syringes that contained EDTA 30ul and inhibitive peptidase 400IU and centrifuged at 3000 rpm/min for 10 minutes to obtain the plasma of subjects. The supernates were then frozen at -70C3. Determination of BG; measuring FPG and 2HPG. 2HPG means the BG level after taking 75g glucose for 2 hours.4. Calculating BMI and waist to hip (WHR) : BMI = body weight (kg)/ height (m2) ; WHR = waist circumference / hip circumference.5. Calculating IR : IR = FINS x FPG/22. 56. Statistical analysis : quantitative data expressed in mean ± SEM . Excell 2000 and SPSS 10. 0 software were used to analyse the data . T test was used and the value of P <0. 05 was considered to be statistically significant.Results1. There were no statistical differences in age between hypertensive subjects ( n = 158) and healthy subjects (n =42). There are statitistical significances in SBP, DBP, BMI and WHR between them (P <0. 05). In group C, BMI (25.81 ±372 kg/m2) was the largest, second to group B(25. 06 ±0. 34 kg/ m2) , and group A was the smallest (24.21 ±0.41 kg/m2). Compairing groupA, group B, group C to control group(23. 15 ±0. 04kg/m2) had dramatically statistical signifIcance(P<0.01). Group A and group B had statistical significance (p <0.05) between them. Group B and Group C had statistical significance (p <0.05).2. There was statistical significance in ET between the hypertesive group and control group, ET (190. 44 ± 34. 76 ng/L) of Group C was the highest, second to group B ( 143. 21 ±11. 30ng/L) , and was also high in group A (97.97 ±9. 13ng/L). The value of these three groups comparing to control group had significant difference ( p < 0. 01). There was a difference between group B and group C(p<0.01). HOMA - IR was the highest in group C (10. 65 ±2. 81mu/L) and also high in group B (5.50 ±0.63 mu/L) and group A (3. 52 ±0. 44 mu/L). These groups comparin更多还原