【作者】 陈明；

【导师】 胡申江；

【作者基本信息】 浙江大学 ， 内科学， 2004， 硕士

【摘要】 背景 高血压病（Essential Hypertension，EH）是中老年人的常见病、多发病。高血压的主要危害是动脉硬化及其导致的心脑肾等重要脏器功能受损。近年来发现血管内皮细胞不仅是保持血管内壁光滑的表面和选择性通透的普通细胞，而且具有内分泌、旁分泌和自分泌的功能。内皮细胞分泌多种血管活性物质，对维持血管壁的张力、血液的流动、管壁的炎症修复和血管的增生具有重要的作用，血管内皮功能障碍在高血压的发生发展中扮演了极其重要的角色。近年来提出了“内皮—高血压—心血管事件”链这一心血管疾病的发展模式。卡维地洛（Carvedilol）是一种新型的β受体阻滞剂，兼有α₁阻滞和抗氧化作用，临床上广泛用于高血压和心衰病人，但其对高血压患者的血管内皮功能尚未见报导。本研究的目的是了解高血压与血管内皮功能障碍的关系，以及卡维地洛对高血压患者血管内皮功能的影响。 方法 1．54例EH患者按1999年中国高血压防治指南进行危险性分层，将32例无靶器官损伤和临床并发症患者分为低危和中危组，22例合并有靶器官受损或临床并发症患者分为高危和极高危组，30例无高血压者作为对照组。三组间性别、年龄无显著差异。利用超声多普勒技术，测定三组研究对象的右肱动脉流量介导的内皮依赖性舒张功能（Flow mediated vasodilatation，FMD）：基础内径Dd、基础血流量Q、血管阻力R、血管顺应性系数CC和血管扩张性系数DC以及反应性充血后的血管内径和血流量的变化D％、Q％、血管阻力R，并测定血浆内皮功能标志物内皮素（ET-1）、血管性假血友病因子（vWF）来评价EH血管内皮功能。 2．然后随机采用氨氯地平（5mg／d）或氨氯地平（5mg／d）+卡维地洛（12.5mg／d）治疗，经12周治疗后复查上述指标。晰江大母硕士李位论文 结果1.基础状态下，三组间血管内径Dd、血流量Q、血管阻力R无显著性差异（乃0.05）2.反应性充血状态下，高危和极高危组内皮依赖性血管扩张D%（6 .6士4.1%）低于正常对照 组（12.1士4.4%）（只0.01）;高危和极高危组肪动脉血流量增加Q%（88士46%）低于对照组 （246士88%）（只0.01）;而血管阻力R在高危和极高危组明显高于对照组（0.081 vs 0.045; 只0 .05）。3.低危和中危组血流量介导的内皮依赖性舒张功能眺与对照组相比有所下降（10.2士4.5% vs 12.1士4.4%），但未达显著性水平（乃0.05）;胧动脉流量增加姚少于对照组（156士86% vs 246士88%），具有统计学差异（只0.05）;而血管阻力已有较明显增加（0.077 vs 0.045; 只0 .01）。4.三组血浆ET一1检查发现，高危极高危组有明显增高（60.4士12.5），与对照组（44.24士 8.9）相比，有显著差异（只0.01）;低危中危组（46.9士14.4）高血压患者与对照组相似 （乃0 .05）。5.三组血浆vwF检查发现，高危极高危组有明显增高（179.3士10.2），与对照组（132.3士 37.4）相比，有显著差异（只0.01）;低危中危组（139.3士45.7）高血压患者与对照组相似 （乃0 .05）。 以上结果，说明高血压患者胧动脉内皮依赖性血管舒张功能以高危极高危组受损明显，低危中危组尚未明显累及。6.高血压患者随机给予氨氯地平或氨氯地平+卡维地洛治疗，12周以后复查上述指标，FMD 资料完整者51例。其中单用氨氯地平29例，联合应用卡维地洛+氨氯地平22例。经随访 发现二组血压控制均较满意，单纯氨氯地平组SBP134.5士H.7;DBP78士6.5;HR72士8。联 合治疗组SBP128.3士10.3;DBP75.7士7.5;HR68士5。联合用药组收缩压控制更理想，与对 照组比较只0.05;二组间舒张压和心率无明显差异（乃0.05）。7.肪动脉内皮依赖性舒张功能D%、姚二组均较前有改善（只0.01），联合治疗组较单纯氨氯 地平治疗组有更明显改善，但未达统计学差异（乃0.05）。血浆ET一，vWF检查二组治疗后 均有显著下降（只0.01），联合治疗组vWF较单纯氨氯地平组有进一步改善（只0.05）。晰江大母硕士母位伦灰 结论 低危和中危组高血压患者内皮功能障碍表现轻微，与对照组差别不显著;尚待进一步增加样本研究。高危和极高危组高血压患者内皮功能障碍明显，肪动脉血流依赖性内皮舒张功能减退明显，同时ET一1、vWF增高。高血压患者在氨氯地平治疗的基础上，加用卡维地洛治疗，血压控制更理想，肪动脉内皮依赖性舒张功能似有改善，但未达到统计学水平，有待继续观察治疗。但ET一1、vwF已有较明显下降，提示卡维地洛可进一步改善高血压患者血管内皮功能。更多还原

【Abstract】 Background: essential hypertension(EH) is a common disease in old and elderly people. The main risk in EH is arteriosclerosis and its complications in heart, brain and kidney. Recent years, it has demonstrated that the endothelium and its dysfunction in arteries has played an important role in the appearance and development of EH and its complications. For this reason , the ACC2003 annual meeting initiate the "vascular-hypertension-cardiovascular event" track to a new spotlight session to illustrated the importance of endothelial function . It has become a common idea at large doctors that "endothelium-hypertension-cardiovascular risk" chain is the most probably track for the cardiovascular diseases. Carvedilol is a new -block drug. It can be able to block the receptors as well as to resist oxidation. It has been prescribed to EH and heart failure widely. But it has not been proved that whether there is a certain benefit to the endothelial dysfunction in EH. The endothelial function on EH and the treatment of Carvedilol on it is required to study further . Method: there are 54 cases of EH diagnosis according to 1999 Chinese guidelines of prevention and treatment hypertension. And 2 groups were divided based on the guidelines with the target damage and complications in the heart and brain and kidney as well as cardiovascular risk . 32 cases were divided as low risk group which the cardiovascular risk is low or middle and 22 cases as high risk group which the risk is high or very high . And there are 30 cases as contrasted group which have normal blood pressure. There are no significant differences in the age and sex among three groups. Detection the flow-mediated vasodilatation(FMD) in right brachial artery by ultrasound in 3 groups were approached: the inner diameter of artery(Dd), velocity of flow(Q) ,vessel resistance (R), cross-sectional compliance(CC) and distensibility coefficient(DC) of the brachial artery in rest as well as which in FMD that is criticized by calculation the increased artery diameter(D%) andflow(Q%) and vessel resistance (R) .Examination the endothelin(ET-l) and Von Willibrand factor(vWF) in fast serum were obtained. The endothelial function were criticized based on above data. Then the EH patients were prescribed Amlodipine 5mg daily or combined Amlodipine 5mg/d plus Carvedilol 12.5mg/d randomly. The endothelium function above were examined repeatedly after 12 weeks long separated treatment.Result 1. There are no significant difference of artery inner diameter(Dd) ,flow(Q) and vessel resistance (R) in the rest among three groups. 2. While FMD, the increased diameter(D%) in the high risk group is lower than that in the contrasted one(6.6 4.1% vs 12.1 4.4%;P<0.01);and the increased flow(Q%) is lower than the contrasted (88 46% vs 246 88%;P<0.01);the vessel resistance (R) is higher in high risk group than that in contrasted(0.081 vs 0.045;P<0.01). 3. The increased diameter by FMD in low risk group is somehow lower than that in contrasted (10.2 卤4.5% vs 12.1 4.4%), but there is no significant difference (.P>0.05).The increased flow (Q%) in low risk group is less than that in contrasted (156 86% vs 246 88%;P<0.05). The artery resistance is certain elevated in low risk group than that in contrasted (0.077 vs 0.045;P<0.01).4. The laboratory examination of ET-1 and vWF in three group have shown that it is similar in low risk group and the contrast group(P>0.05), but it is elevated in high risk group than that in contrasted(,P<0.05). It means that the endothelial function of brachial artery in EH is seriously impaired in high risk group, but not occurred obviously in low risk group. 5. After twelve weeks treatment with Amlodipine 5 milligram diary alone or Amlodipine 5 milligram plus Carvedilol 12.5 milligram combined randomly, the data above, of endothelial function have been examined again. There are 51 cases have been examined by ultrasound. There are 29 cases prescribed Amlodipine solely and 22 cases combined with Carvedilol. Both the blood pressure are controlled well after 12 w更多还原