【作者】 张誉洋；

【导师】 王海昌； 马进；

【作者基本信息】 第四军医大学 ， 内科学， 2007， 硕士

【摘要】 心血管疾病目前是世界上发病率和死亡率最高的疾患之一。血流动力学状态的变化对血管结构和功能有着重要的影响。诸如动脉粥样硬化、血栓形成、心肌梗死、高血压、冠心病等常见心血管疾病的发生都与动脉血管中的血液流动密切相关。血液流动区域内压力、速度、管壁切应力的变化,可以通过影响动脉血管平滑肌细胞和内皮细胞的适应性机制,导致血管壁发生病理改变。甲状腺功能亢进会造成动脉血管血液流动区域内的压力增高、速度加快、管壁切应力变大;模拟失重将导致冠状动脉系统灌注压下降,血流减少,血液流动区域内的压力下降、速度减慢、管壁切应力变小。这两种高、低不同的血流动力学状态与心血管疾病的关系还缺乏深入系统的研究。因此可以通过深入研究不同血流动力学状态对动脉血管的影响,来更好地了解心血管疾病的发病机理。目的通过研究甲状腺功能亢时动脉内血液流动的高动力状态及模拟失重时冠状动脉内血液流动的低动力状态对血管反应性的影响,了解心血管疾病的发病机理及航天飞行后立位耐力不良的发生机理。方法建立甲亢大鼠模型及尾部悬吊模拟失重大鼠模型。采用离体动脉血管环技术研究甲亢大鼠肾动脉、肠系膜动脉、股动脉、颈总动脉和脑基底动脉、肠系膜分支小动脉血管反应性的改变,以及模拟失重大鼠冠状动脉血管反应性的改变;利用光镜、电镜技术对模拟失重大鼠冠状动脉组织形态及超微结构的改变进行观察;利用蛋白免疫印迹技术测定动脉中eNOS和iNOS蛋白表达。结果1、甲亢时高血流动力学状态下,大鼠肾动脉、肠系膜动脉、股动脉、颈总动脉对KCl和PE的收缩反应性降低,对ACh的舒张反应性增强,对SNP的舒张反应无明显改变。甲亢大鼠各部位动脉对KCl、ACh敏感性增加,对PE、SNP敏感性没有明显改变。2、甲亢时高血流动力学状态下,大鼠脑基底动脉、肠系膜分支小动脉血管对KCl和5-HT或PE的的收缩反应性降低,对ACh的舒张反应性增强,对SNP的舒张反应无明显改变。甲亢大鼠各部位小动脉对KCl、ACh敏感性增加,对5-HT或PE、SNP的敏感性没有明显改变。3、甲亢大鼠肠系膜分支小动脉和基底动脉中eNOS蛋白表达量显著增多;甲亢大鼠肠系膜分支小动脉和基底动脉中检测到iNOS蛋白表达,而对照组中未检测到iNOS蛋白表达。4、两周模拟失重大鼠冠状动脉对KCl和PE的收缩反应性降低,对ACh、SNP的舒张反应性降低;对KCl、ACh的敏感性下降,对PE、SNP敏感性没有明显改变。5、两周模拟失重大鼠冠状动脉组织形态及超微结构观察发现,血管平滑肌萎缩,血管内皮细胞发生病理改变。6、两周模拟失重大鼠冠状动脉中eNOS蛋白表达显著降低;在模拟失重组及对照组大鼠冠状动脉中均未检测到iNOS蛋白表达。结论甲亢时高血流动力学状态可能通过对血管平滑肌细胞及内皮细胞的影响,使动脉血管收缩反应性减弱、内皮依赖的舒张反应性增强;高血流动力学状态可能通过NO的增加,来使高切应力下血管的内皮依赖性舒张增强。模拟失重大鼠冠状动脉低血流动力学状态对冠状动脉产生了显著影响,冠状动脉收缩及舒张反应性均减弱,血管内皮细胞和血管平滑肌结构和功能发生病理改变,此变化在航天飞行后立位耐力不良及其他心血管疾病的发生机制中可能具有重要作用。更多还原

【Abstract】 Cardiovascular disease is one of the most challening diseases in modernworld.The change of haemodynamic states significantly affects arterial structureand function.The hemokinesis in artery has great relationship with pathogenesis ofcardiovascular disease,such as artherosclerosis, thrombogenesis, heart infarction,hypertension and coronary artery disease.Alterations of pressure, velocity, andshear stress in artery result in pathological change of vessel wall,throughinfluencing adaptable mechanism of vascular smooth muscle cell and endothelialcell.Hyperthyroidism causes increased pressure,high speed and big shear stresswithin the arterial blood flow region.Whereas simulated weightlessness leadscoronary system to low perfusion pressure, reducing blood flow, therefore withinthe coronary arterial blood flow region it causes decreased pressure,low speed andsmall shear stress. But there is no in-depth and systematic research about therelationship between these high or low haemodynamic states and cardiovasculardisease.So we can get a better understanding of cardiovascular diseasepathogenesis through in-depth and systematic study of alterations in arterialreactivity under different haemodynamic states. AIMAIMS Through studying alterations in arterial reactivity of various arteriesin rats under hingh haemodynamic state of hyperthyroidism and lowhaemodynamic state of simulated weightlessness,to understand the pathogenesisof cardiovascular disease and the mechanism of orthostatic intolerance after spaceflight.METHODS Established hyperthyroid rat model and simulated weightlessnessrat model. By means of isolated arteries ring technology,studied alterations inarterial reactivity of renal artery,mesenteric artery,femoral artery,carotidartery,basilar artery, small mesenteric branches artery in hyperthyroid rats andcoronary artery in simulated weightlessness rats. Using light microscopy andelectron microscopy,observed morphology and ultrastructure changes of coronaryartery of simulated weightlessness rats.The eNOS and iNOS protein expressionswere observed by Western Blot technique.RESULTS1、The isometric contractile tensions evoked by KCl（10～100 mmol/L）andphenylephrine (PE) (10-9～10-4 mol/L)were significantly lower in renalarterial,mesenteric arterial,femoral arterial,carotid arterial rings from hyperthyroidrats compared with those of control ones (P<0.05). The vasodilator responseinduced by acetylcholine (ACh) (10-9～10-4 mol/L)was significantly increased inhyperthyroid group (P<0.05). But the differences of responses of those arterialrings induced by sodium nitroprusside (SNP) (10-9～10-4 mol/L)between twogroups were nonsignificant. The sensitivities of those arterial rings to KCl andACh were significantly enhanced by hyperthyroidism (P<0.05), whereas thesensitivity to PE and SNP did not show any significant differences between twogroups. 2、The isometric contractile tensions evoked by KCl and 5-HT or PE weresignificantly lower in basilar and small mesenteric branch arterial rings fromhyperthyroid rats compared with those of control ones (P<0.05). The vasodilatorresponse induced by ACh was significantly increased in hyperthyroid group(P<0.05). But the differences of responses of those arterial rings induced bysodium SNP between two groups were nonsignificant. The sensitivities of thosearterial rings to KCl and ACh were significantly enhanced by hyperthyroidism(P<0.05), whereas the sensitivity to 5-HT or PE and SNP did not show anysignificant differences between two groups.3、The eNOS protein expression increased in basilar and small mesentericbranch artery of hyperthyroid rats compared with those of control ones (P<0.05).The iNOS protein expression occured in hyperthyroid rats but didn’t occure incontrol ones.4、The isometric contractile tensions evoked by KCl and PE weresignificantly lower in coronary arterial rings from two weeks simulatedweightlessness rats compared with those of control ones (P<0.05). The vasodilatorresponse induced by ACh and SNP were significantly decreased in simulatedweightlessness group (P<0.05).The sensitivities of those arterial rings to KCl andACh were significantly decreased by simulated weightlessness (P<0.05), whereasthe sensitivity to PE and SNP did not show any significant differences betweentwo groups..5、Morphology and ultrastructure changes of coronary arteries of two weekssimulated weightlessness rats were observed: pathological changes took place invascular endothelial cells and vascular smooth muscle was atrophical.6、The eNOS protein expression decreased in coronary arteries of two weeks simulated weightlessness rats compared with those of control ones (P<0.05). TheiNOS protein expression didn’t occure in two groups.CONCLUSION The high haemodynamic state of hyperthyroidism maybethrough influencing adaptable mechanism of vascular smooth muscle cell andvascular endothelial cell caused arteriel vasoconstriction weaken and theendothelium-dependent vasodilator response increase.The vascular endotheliumdependentvasodilation increased under high haemodynamic state maybe bymeans of the enhancement of NO. The low haemodynamic state of simulatedweightlessness significantly affected coronary arterial structure and function.Thecoronary arterial vasoconstriction and vasodilator response both decreased, andpathological changes took place in vascular endothelial cells and vascular smoothmuscle cells.This change may paly a role in pathogenesis of cardiovasculardisease and the mechanism of orthostatic intolerance after space flight.更多还原