肾血管性高血压大鼠的大脑表面侧支吻合血管改变

高血压脑动脉硬化是脑梗塞的主要危险因素之一。我们已复制了可靠而稳定的肾血管性高血压大鼠(RHR)模型,并观察到RHR脑血管的形态结构改变。本研究用脑血管铸型方法,实验比较RHR与正常血压大鼠的脑表面侧支吻合血管情况,旨在探     

西比灵对脑缺血再灌注后HSP70表达的影响

血诱导神经细胞表达的热休克蛋白70(HSP70),被认为在脑缺血引起的损伤中具有脑保护作用.西比灵选择性阻断Ca2+过度内流,减轻缺血性神经损伤.本文用肾血管性高血压大鼠(RHR)制作脑缺血再灌注模型,评价西比灵对脑缺血再灌注损伤的保护作用并探讨其脑保护机制.选用纯种健康远交雄性Wistar大鼠36只,制作成肾血管性高血压大鼠并随机分组,采用Longa等人的方法加以改良制备大脑中动脉闭塞(MCAO)模型.术前,西比灵干预组大鼠腹腔注射新鲜配置的西比灵混悬液(1 mg@kg-1),脑缺血再灌注组和假手术组大鼠腹腔注射等容积的生理盐水.     

自发性高血压大鼠脑底动脉神经肽Y能神经纤维的分布

应用免疫组织化学技术ABC法,对10只雄性自发性高血压大鼠脑底动脉神经肽Y能神经纤维分布进行了观察.在自发性高血压大鼠脑底血管的大脑前动脉、大脑中动脉、大脑后动脉和基底动脉壁上均可见棕褐色的免疫反应阳性纤维,纤维较粗,曲线状,呈网状分布,密度较高.与正常血压大鼠同一部位脑底动脉血管壁上的阳性纤维密度相比明显增加.结果表明:高血压大鼠脑底动脉各主要分支较正常血压大鼠脑底动脉各主要分支有更高密度的神经肽Y能神经纤维分布,提示高密度的神经肽Y能神经可能在高血压大鼠脑血管的神经营养和神经调节方面起着重要的作用.     

美托洛尔抗高血压预防脑卒中的实验病理学研究

目的探讨抗高血压治疗预防脑卒中的形态学机制。方法采用易卒中型肾血管性高血压大鼠口服美托洛尔治疗，观察抗高血压治疗各级脑动脉和心室壁厚度的形态学改变。结果治疗组大鼠血压仅短期轻度低于未治疗的高血压对照组，但治疗组各级脑动脉损害和左心室肥厚明显改善，脑卒、中发生率也显著低于高血压对照组。结论美托洛尔抗高血压治疗预防脑卒中的效果，不单纯由血压下降决定，还与其具有保护脑血管和逆转心室肥厚等作用有关。     

临界关闭压对高血压大鼠脑血流的调控作用

目的 探讨临界关闭压（critical closing pressure,CCP）对肾血管性高血压大鼠（renovascular hypertensive rats,RHR）脑血流动力学改变的调控作用。方法 RHR模型（RHR组）26只,假手术正常血压对照组24只,同步记录大脑中动脉血流速度（cerebral blood flow velocity,CBFV）和有创血压,按照CCP理论计算CCP和小动脉阻力,并分析血流动力学参数之间,以及血流动力学参数与血管形态参数改变间的关系。结果 与对照组比较,RHR组动脉血压明显升高的同时,脑循环有效灌注压（effective cerebral perfusion pressure,CPPe）和血管面积阻力指数（resistance area product,RAP）明显升高（CPPe：100.80±26.40 mmHg vs 67.30±13.10 mmHg,P<0.01;RAP：2.94±0.85 vs 2.30±0.59,P=0.003）,但CBFV相对稳定,脑循环阻力（cerebral vascular resistance,CVR）升高不明显。RHR组血管面积阻力指数（resistance area product,RAP）只与小动脉管腔内径呈负相关（rs=-0.610,P=0.001）,CCP与小动脉中膜厚度呈正相关（rs=0.554,P=0.006）;而CVR不仅与小动脉管腔内径呈负相关（rs=-0.463,P=0.023）,也与小动脉中膜厚度呈正相关（rs=0.678,P＜0.01）。结论 RHR的脑血流调控可通过CCP和RAP的改变来完成,用CCP和RAP代替CVR,能更加真实、客观地反映脑血流动力学的调控机制。     

高胆固醇、高血压对大鼠脑动脉内皮糖萼的作用

目的分别给易卒中型肾血管性高血压大鼠、正常血压大鼠饲以高脂饲料6周和16周,在电镜下观察其脑动脉内皮糖萼的变化。结果高胆固醇可引起大鼠颈内动脉、大脑中动脉内皮糖萼变薄、分布不均匀,常伴缺失、结块现象,且高胆固醇时间越久、损害越严重。高血压也可引起大鼠大脑中动脉内皮糖萼同样的改变。这在增加脑血管的通透性,促进脂质的沉积和动脉粥样硬化的形成中可能起重要作用。     

高血压在局部脑梗塞边缘区和镜区脑超微结构的动态改变中的意义

本文实验发现双肾双夹肾血管性高血压大鼠（RHR）在大脑中动脉闭塞（MCAO）后1-7天，梗塞灶边缘区有脑微血栓形成，MCAO后3天对侧半球的相应区（镜区）有较明显的微血管变形和星形细胞足突水肿改变，说明RHR与正常的SD鼠在局灶脑梗塞后的超微结构改变是不同的。因此，我们应当重视高血压的防治。     

肾性高血压大鼠脑动脉瘤形成过程中血浆内皮素-1的变化

目的:模拟人类高血压致大脑动脉瘤的病理过程,利用肾性高血压及脑血流动力学变化制备大鼠脑动脉瘤模型,通过观测脑动脉瘤形成过程中大鼠血浆内皮素一1(ET-1)的变化,探讨ET-1在脑动脉瘤发生发展中的作用。方法:将雄性SD大鼠随机分为肾性高血压组(RH)、假手术组,体重为200～250g,自发性高血压(SHR)大鼠购自中国医学科学院动物所,于术后1周、2周、4周、8周、12周、16周分别测定大鼠尾动脉收缩压、血浆ET-1含量。手术16周后处死动物,在光镜下观察脑动脉瘤的发生及部位。结果:①RH及SHR大鼠在术后第2周血压开始升高,血浆ET-1水平随血压升高而增加,在术后第4周时达到高峰,两组大鼠血压及血浆ET-1含量均明显高于同期假手术组。②在手术16周后处死动物,其中10只SHR大鼠、6只RH大鼠形成脑动脉瘤,有脑动脉瘤形成的大鼠血浆ET-1水平明显高于同组未形成动脉瘤的大鼠。③结论:肾性高血压时,随着血压增高缩血管物质ET-1血浆水平增高,ET-1可能通过导致脑血管内皮细胞功能紊乱、血管内皮结构破坏参与了脑动脉瘤的形成。     

尼维地平抗高血压治疗对大鼠局灶脑缺血的保护作用

选用１２周的自发性高血压在大鼠，皮下植入随渗透泵予尼维地平或其溶剂７ｄ（第１组）或１４ｄ（第２组）。用药后分别于第６、１３ｄ阻断左侧大脑中动脉。尼维地平治疗组血压降至正常，第１、２组应用尼维地平治疗后，梗塞灶体积较各自的对照组减少，冠状连续切片上梗塞灶面积在第１组仅有２张，而在第２组有５张缩小。第２组脑水肿体积亦减少。因此尼维地平对自发性高血压大鼠的局灶缺血具有疗程相关的保护作用，提示长期应用该药     

氯沙坦对卒中易感型自发性高血压大鼠的脑保护作用

目的 研究氯沙坦对卒中易感型自发性高血压大鼠(SHRsp)脑保护作用的机制。方法 6周龄雄性SHRsp随机分为生理盐水组、小剂量氯沙坦组(10mg·kg-1·d-1)和大剂量氯沙坦组(30mg·kg-1·d-1),记录血压和脑卒中临床表现评分,18周后处死,光镜观察脑卒中的发生率和脑血管结构;电镜观察脑组织的超微结构;TUNEL法检测神经细胞凋亡。结果 大剂量氯沙坦组血压明显低于未用药组(PO.05)。对照组SHRsp死亡率、脑动脉中膜厚度/管腔半径的比值和神经细胞凋亡率均高于小剂量和大剂量氯沙坦组,差异均有显著性意义(P相似文献   

Effects of acute hypertension on brain metabolism in normotensive, renovascular hypertensive and spontaneously hypertensive rats

Effects of angiotensin-induced acute hypertension on cerebral metabolism were studied in normotensive (NTR), spontaneously hypertensive (SHR) and experimental renovascular hypertensive rats (RHR). Lactate, pyruvate and adenosine triphosphate (ATP) concentrations in the brain frozen in situ at 18--20 min after angiotensin infusion, which raised mean arterial pressure (MAP) by 28--62% of control, were determined by enzymatic methods. Supratentorial lactate was significantly increased to 135% of control in RHR, its increase being correlated with the degree of hypertension, wherease it remained unchanged in NTR or SHR. Furthermore, RHR showed a tendency toward increase in lactate/pyruvate ratio with a decrease in ATP despite no change of arterial acid-base balance measured simultaneously before and after acute induced hypertension. From the present study, it is postulated that some renal factor seems to contribute ischemic metabolic changes in RHR following acute hypertension. The possible effect of renin on the vascular permeability is discussed as the pathogenesis of hypertensive encephalopathy.     

ET、CGRP水平在高血压及局部脑缺血后下丘脑和血浆中的动态变化

本实验动态测定了肾性高血压大鼠（ＲＨＲ）不同时期下丘脑和血浆ＥＴ和ＣＧＲＰ水平的变化以及局部脑缺血后不同时期的改变，并与正常血压的ｗｉｓｔａｒ鼠对比。结果发现，形成稳定高血压的３月龄ＲＨＲ和７月龄ＲＨＲ其下丘脑和血浆中的ＥＴ含量均明显高于同龄Ｗｉｓｔａｒ鼠，而ＣＧＲＰ含量无显著差异。局部脑缺血后２４小时，无论ＲＨＲ还是Ｗｉｓｔａｒ鼠，其下丘脑和血浆ＥＴ和ＣＧＲＰ均比缺血前明显增高（Ｐ＜０．０１），以ＲＨＲ更加明显。缺血持续７天时，ＥＴ和ＣＧＲＰ在Ｗｉｓｔａｒ鼠全部恢复至缺血前水平，而在ＲＨＲ下丘脑和血浆中ＣＧＲＰ含量恢复至缺血前水平，ＥＴ含量仍明高于缺血前水平。结果提示，高水平的ＥＴ含量可能参与了ＲＨＲ高血压的形成和发展，而局部脑缺血后，ＲＨＲ中枢和外周ＥＴ大量持续释放不利于缺血区域侧支循环血管的开放，此可能是高血压性脑梗塞恢复慢，疗效差的原因之一．     

Brain metabolism following bilateral carotid occlusion in 2 different models of experimental hypertensive rats

Brain metabolites and arterial acid-base measurements were made one hr after bilateral carotid artery occlusion in 2 different models of hypertensive rats. Animals used included renovascular hypertensive rats (RHR) with an altered renin-angiotensin system and desoxycorticosterone hypertensive rats (DHR) with low plasma renin activity (PRA). The mean value for supratentorial lactate of 7.41 mM/kg in RHR was significantly higher than in DHR (3.90 MM/kg) or in control normotensive rats (3.10 - 2.56 mM/kg). Concomitantly, the lactate/pyruvate ratio tended to increase and ATP to decrease in RHR only. In these same rats (RHR) infratentorial lactate was also increased. The results suggest that bilateral carotid occlusion leads to anaerobic metabolism of the brain in RHR but not in DHR, suggesting that the renin-angiotensin system may play some role in the susceptibility to cerebral ischemia following carotid occlusion in the hypertensive rats.     

Protective effects of angiotensin II type 1 receptor blocker on cerebral circulation independent of blood pressure

Angiotensin II type 1 receptor (AT1R) blocker (ARB) has been reported to modify hypertensive cerebrovascular changes; however, it is not clear whether its protective effects are independent of blood pressure. The aim of this study was to clarify the role of AT1R-mediated signals in cerebral circulation by the chronic treatment with telmisartan, an ARB, at a dose that did not lower the blood pressure. Male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were treated for 4 weeks from 16 weeks of ages with telmisartan (SHR-L: 0.3 mg/kg/day, SHR-H: 3 mg/kg/day, WKY-H: 3 mg/kg/day) or vehicle (SHR-V, WKY-V). Superoxide measured by a chemiluminescent assay or dihydroethidium fluorescence and vascular morphology were examined for the thoracic aorta (Ao), common carotid (CCA), middle cerebral (MCA) and basilar arteries (BA). After 4 weeks of treatment, the blood pressure significantly declined in SHR-H but not in SHR-L in comparison to SHR-V. The lower limit of cerebral blood flow (CBF) autoregulation, evaluated by hemorrhagic hypotension, was significantly lower in SHR-L and SHR-H than SHR-V. In both SHR and WKY, the superoxide levels in the arteries were significantly attenuated by both doses of ARB. ARB also reversed vascular hypertrophy in Ao, CCA and BA and the inward remodeling in MCA. These results suggest that chronic treatment with telmisartan may therefore improve CBF autoregulation with a restoration of the vascular structure and an attenuation of superoxide generation, even at a dose that does not lower the blood pressure.     

高血压大鼠局部脑缺血再灌流边缘区超微结构改变

用透射电镜观察了肾血管性高血压大鼠局部脑缺血早期再灌流及持续缺血９个实验组和假手术组缺血边缘区超微结构改变。结果发现：局部脑缺血０．５至３小时再灌流均较相应持续缺血神经元损害轻；缺血６小时再灌流，神经元细胞器固缩，并有暗黑颗粒沉积。表明在高血压鼠局部脑缺血早期，恢复血流有利于边缘区神经元恢复。     

银夹形状对肾血管性高血压大鼠远期血压及并发症的影响

观察不同形状银夹对肾血管性高血压大鼠远期血压及并发症的影响。　　方法　用内径均为 0 3mm的环形和槽形银夹分别复制双肾双夹型肾血管性高血压大鼠 ,记录两组大鼠在肾动脉狭窄术后 3 0周内的血压水平、自发脑卒中率和心肌梗塞率。　　结果　肾动脉狭窄术后 1～1 4周内 ,两组血压无显著性差异 ,1 4周后环形银夹组血压高于槽形银夹组 ,3 0周内自发脑卒中率和心肌梗塞率也高于槽形银夹组。　　结论　用环形银夹复制的双肾双夹型肾血管性高血压大鼠模型 ,更适用于高血压性心、脑并发症的研究     

肾血管性高血压大鼠脑梗塞后脑微血管形态计量学动态观察

本研究选用双肾双夹肾动脉狭窄术复制成的肾血管性高血压大鼠（ＲＨＲ）５４只；同龄正常血压鼠（ＳＤＲ）５４只，各分为大脑中动脉闭塞（ＭＣＡｏ）前、后不同时间的９个实验和对照组，各组均即时从心腔等压灌注中华墨汁，取脑顶叶梗塞灶边缘区，行冠状、矢状、水平三方向取材，制片，在显微镜下作微血管形态计量学测定．结果显示ＲＨＲ顶叶脑皮质毛细血管直径、单位体积毛细血管长度、表面积、通过２００μｍ的毛细血管支数均较ＳＤＲ减少，表明高血压可致脑微血管稀疏；同时观察到局部脑梗塞后上述反映毛细血管网三维构筑的参数变化远较对照鼠明显，缺血后脑损伤更严重。说明毛细血管损伤程度与梗塞灶的大小直接相关，因此应加强高血压的防治，以保护脑微血管立体构筑。     

Influence of antihypertensive treatment with budralazine on autoregulation of cerebral blood flow in spontaneously hypertensive rats

We studied the effect of chronic antihypertensive treatment with budralazine on the lower blood pressure limit of cerebral blood flow autoregulation using spontaneously hypertensive rats. Cerebral blood flow in the parietal cortex and caudate nucleus was measured to determine the lower limit using the hydrogen clearance method. The lower limit in both cerebral regions was significantly higher in 10 untreated spontaneously hypertensive rats than in 10 Wistar-Kyoto rats. The upward-shifted lower limit was restored to close to normal in the caudate nucleus and was partially restored in the parietal cortex of nine rats by 9 weeks of treatment with the high dose (50-68 mg/kg/day) of budralazine, which kept blood pressure constant at approximately normotension during the treatment period; the lower limit was slightly restored in both cerebral regions of seven rats by 4 weeks of treatment with the high dose. However, 9 weeks of treatment with the low dose (19-27 mg/kg/day) of budralazine, which produced moderate continuous hypotension in nine rats, did not apparently influence the lower limit. Our results suggest that long-term antihypertensive therapy with budralazine reduces the upward-shifted lower blood pressure limit of cerebral blood flow autoregulation toward normal and that the restoration induced by budralazine depends on the degree of blood pressure reduction as well as on the duration of the therapeutic period.     

肾血管性高血压鼠及局部脑缺血后下丘脑和血浆中内皮素、降钙素基因相关肽水平的变化

实验测定了肾血管性高血压大鼠（ＲＨＲ）不同鼠龄下丘脑和血浆ＥＴ、ＣＧＲＰ水平以及局部脑缺血后不同时期的变化。结果发现，３，７月龄ＲＨＲ其下丘脑和血浆中的ＥＴ水平明显高于对照鼠。局部脑缺血组１天，ＲＨＲ和对照鼠的下丘脑及血浆中ＥＴ、ＣＧＲＰ水平均比缺血前增高，缺血７天时，对照鼠ＥＴ、ＣＧＲＰ均恢复至缺血前水平，而在ＲＨＲ，下丘脑和血浆ＥＴ仍高于缺血前水平，提示：高水平的ＥＴ可能参与了ＲＨＲ高血压的形成和发展，而局部脑缺血后，ＥＴ大量持续释放，可能是导致高血压性脑梗塞患者恢复慢，疗效差的原因之一。