阿司匹林对高血压性脑卒中预防作用的实验研究

目的 观察阿司匹林对高血压性脑卒中的预防作用,为临床应用提供依据.方法 按已定型的双肾双夹法建立易卒中肾血管高血压大鼠模型,12周后应用人工寒潮引发卒中.预防组给予阿司匹林,假手术组和实验对照组用等剂量植物油,连续7d后,置于人工寒潮箱3d诱发脑卒中;之后,取脑TTC染色、常规病理HE染色以统计卒中灶数目.结果 阿司匹林可以减少卒中发生率、卒中体积.结论 阿司匹林可以减少卒中的发生及梗死体积.     

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     

易卒中肾血管性高血压大鼠血液流变学分析

目的 探讨易卒中肾血管性高血压大鼠血液流变学的变化。方法 运用双肾双夹法建立易卒中肾血管性高血压大鼠模型,常规饲养4个月后检测其血液流变学的变化。结果 术后4个月,易卒中肾血管性高血压大鼠的低切、中切、高切全血粘度、红细胞比积、低切全血还原粘度均显著高于正常血压大鼠。结论 易卒中肾血管性高血压大鼠具备了高血压病的血液流变学改变,是研究高血压性脑卒中的理想模型。     

肾血管性高血压鼠与自发性高血压鼠脑血管损害的病理观察

为了解自发性高血压与肾血管性高血压所致脑血管病理损害的异同点。本研究用１５只自发性高血压大鼠（ＳＨＲ）和通过狭窄双侧肾动脉复制１５只肾血管性高血压大鼠（ＲＨＲ），分阶段动态观察两者脑内动脉管壁的病理变化。结果发现两种高血压动物的脑血管病理损害均是随着鼠龄增长及高血压的长期持续存在，由轻到重逐渐发展的，后期两者都有血管壁玻璃样变性，纤维素样坏死，自发性脑卒中出现。表明无论是原发性高血压还是继发性高血压，其所致的脑血管病理损害是相似的。     

高血压动脉硬化性混合性中风的实验病理学研究

用双肾双夹法复制易卒中型肾血管性高血压大鼠55只,肾动脉狭窄术后40周内自发脑卒中31只,其中单纯出血或缺血性中风20只(64.5％),混合性中风11只(35.5％)。混合性中风的大鼠脑内细小动脉的透明变性、纤维素样坏死、微动脉瘤形成及增生性反应等病变比单纯出血或缺血性中风者更为广泛、严重。表明高血压是混合性中风的重要病因,高血压性血管损害是其发病基础。本文还根据中风灶的大小将混合性中风进一步分型,并探讨了各型的发生机制。     

大鼠脑血栓溶解和亚低温联合治疗的研究

选用纯种健康雄性Spraque-Dawley大白鼠,行双肾双夹肾动脉狭窄术.双肾动脉狭窄术后高血压持续8～10周以上,血压达24 kPa或以上,从未出现脑卒中神经系统症状的肾血管性高血压大鼠(RHRSP)用光化学法制成一侧大脑中动脉闭塞(MCAO)模型,在MCAO后0.5、1、2、3小时应用尿激酶静脉溶栓,结合亚低温治疗,用TTC染色和HE染色,观察溶栓治疗和亚低温联合治疗对梗塞灶大小的影响以及溶栓复流后脑出血情况.     

肾血管性高血压大鼠自发脑卒中与左心室肥厚的关系

目的探讨高血压个体脑卒中与左心室肥厚的关系。方法比较易卒中型肾血管性高血压大鼠发生与未有脑卒中的血压水平及左心室肥厚程度，观察经１０周抗高血压后，其脑卒中与血压和左心室肥厚的关系。结果脑卒中大鼠的血压水平及左心室肥厚程度比未卒中者更高。抗高血压后期，其血压水平与高血压对照组无显著性差异，但随着左心室肥厚的减轻，脑卒中率显著降低。结论左心室肥厚和脑卒中均为高血压的并发症，而前者不是后者的独立危险因素。减轻左心室肥厚的抗高血压治疗，即使降血压轻微，对预防脑卒中仍有意义     

实验性高血压所致的颈动脉损害

为了探讨高血压性颈动脉损害与血压水平的关系及其在脑卒中发病中的意义，将易卒中型肾血管性高血压大鼠的颈总动脉进行了形态学测量，并观察了硝苯吡啶、卡托普利和美托洛尔抗高血压治疗后这些测量参数的改变。结果发现，易卒中型肾血管性高血压大鼠的颈动脉损害主要表现为中层肥厚，由平滑肌细胞增生、肥大、弹力纤维增多和管壁重构引起。抗高血压治疗后，平滑肌细胞的增生、肥大受到抑制，但弹力纤维增多和管壁重构无改善。提示脑动脉管壁结构未能恢复正常是抗高血压治疗不能完全防止脑卒中的原因之一。     

易卒中型肾血管性高血压大鼠模型

用内径为0.30mm的银夹钳夹双侧肾动脉,复制出一种易卒中型肾血管性高血压大鼠模型,其血压峰值高且稳定在26.7kPa以上,并发生与人类高血压病类似的脑动脉损害:细小动脉纤维素样坏死、透明变性和微动脉瘤形成等,在此基础上,0.56的大鼠自发产生各种类型的脑卒中:脑梗塞、脑出血、蛛网膜下腔出血和混合性脑卒中。本文还着重将这种易卒中型肾血管性高血压大鼠与易卒中型自发性高血压大鼠作了比较。     

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。     

西比灵对大鼠高血压性脑血管病变作用的研究

目的 探讨西比灵对大鼠高血压性脑血管病变的作用及其机制。方法 建立肾血管性高血压大鼠（RHR）模型。用插胃管法喟食西比灵对RHR进行治疗，观察动脉血压，脑血流速度和脑血管形态的改变。结果 用药2-4周动脉血压明显低于同期未用药RHR，4-6周后脑底动脉内腔面积，横断面积，中膜厚度等明显好于未用药RHR，这些作用可以持续2-4周。结论 在高血压早期，西比灵可以降低RHR的动脉血压，阻止脑血管损害的发展。     

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.     

Stroke-prone renovascular hypertensive rats

Purpose To summarized the methods for establishment, characteristics of vascular lesions in brain and heart and thc application of stroke-pronc renovascular hypertensive rats (RHRSP). Background Spontaneously hypcrtensivc rats (STR) and subtypes of SH R, especially stroke-prone spontaneously hypertensive rats (SHRSP) are considered as most important animal models at present for the studies of hypertension and its complications in heart and brain, evcn SHRSP arc considered as thc unique animal model in which prcvention of stroke can be studied cxperimentally Howcver, the applications of SHR and SHRSP are limited because of the effects of genetic deficits and thc difficulties with breeding Theretore, most of the researches on experimental stroke have been performed on the animal models with normotcnsion and normal structure of cerebral vessels. In fact, there are great differences in structure of cerebrovesscls, autoregulation of cerebral blood flow and extent of lesions in brain tissue, even the reaction to the medication after ischemia between the animals with extcnsive arteriosclerosis and with normal cerebral blood vessels. Obviously, thc relevancc of experimental stroke on normal animals to the stroke on cerebral arteriosclerotic patients clinically remains dubious. Data sources and methods Most published original articles about RHRSP in our laboratory were reviewed Results After the renal arteries were constricted bilaterally with ring-shape silver clips, the stroke-prone rcnovascular hypertensive rats were established. Hypertension was produced in all RHRSP(100%).The peak of blood pressure in RHRSP reached 29.1 ±3.0kPa. The lesions of cerebral arteries and arterioles and the damage of cerebral capillary structure by hypertension were observed in the RHRSP. The incidence of spontaneous stroke was 56.4% with in 40 weeks after the renal artery constriction. Left ventricular hypertrophy and small coronary arterial lesions in myocardium were discovered in all RHRSP. Myocardial infarction occurred spontaneously in 41.8% of RHRSP. The animal models have been used for the studies on mechanisms of stroke and myocardial infarction. Futhermore, RHlRSP with cercbrovascular basal pathological changes can be induced as cerebral thrombosis by thc photochemical method, which is quite similar to that of human being in evolution. Therefore. RHRSP with photochemical cerebral thrombosis can be used to appraised therapeutic effects of medication more objectively Conclusions Because the vascular lesions in cerebrum and heart in RHRSP are similar to that in human beings with hypertension, RHRSP can be used in the studies on mechanisms of hypertensive arterioscle-rotic stroke and cardiac lesions and on verifying the effects of different medications to complications of hypertension, and thc results might be more reliable than that in animal models without hypertension.     

Cerebral infarction following bilateral carotid artery ligation in normotensive and spontaneously hypertensive rats: a pathological study.

A pathological examination was performed on normotensive rats (NTR) and spontaneously hypertensive rats (SHR) following bilateral common carotid artery ligation. After ligation, diffuse and extensive cerebral infarcts in the carotid artery territory occurred frequently in SHR, while NTR occasionally had well-circumscribed small infarcts. The posterior communicating arteries, which are the major anastomotic channels connecting the carotid and vertebrobasilar systems, did not show any anomalies and were well developed in SHR and NTR. Vascular changes secondary to hypertension, such as fibrinoid necrosis or thickening of the wall, were not observed in SHR. Because of the paucity of structural difference of the blood vessels, the more diffuse and extensive cerebral infarcts in SHR after carotid occlusion were attributed to the hemodynamic difference rather than the morphological difference between the two groups. The results of the present experiment suggest that hypertension per se, i.e., hemodynamic factors, may be operative for the development of cerebral infarction.     

Serial magnetic resonance imaging of rat brain after induction of renal hypertension.

BACKGROUND AND PURPOSE: Hypertension is a major risk factor for ischemic and hemorrhagic stroke and may also cause more chronic and subtle brain injury. Progressive brain changes in a rat model of renal hypertension have been assessed to better understand the pathogenesis of hypertensive brain damage. METHODS: Young adult rats were made hypertensive by partial occlusion of both renal arteries. MR images of brain were obtained weekly, and histopathological outcome was assessed. A separate group of rats was used to measure brain specific gravity and Evans blue dye content as an indicator of extravasation. RESULTS: Rats developed maximal mean systolic blood pressures of 173 to >300 mm Hg, reaching a plateau in 6 to 8 weeks. Rats whose mean systolic pressure never exceeded 210 mm Hg never had brain lesions, while rats whose mean systolic pressure exceeded 276 mm Hg consistently developed brain lesions. Brain T2 values increased with increasing blood pressure. Lesions seen on MRI corresponded to those seen histologically. MRI also demonstrated transient brain expansion, probably due to diffusely increased water content, and rarely demonstrated focal cortical edema, which had no histological correlate. These transient phenomena, as well as hemorrhagic and ischemic infarcts, occurred mainly during the phase of climbing blood pressure and early stages of stable hypertension. CONCLUSIONS: Serial MRI reveals aspects of hypertensive brain disease that cannot be studied by histological examination alone. The observed phenomena are likely related to loss of autoregulation and/or blood-brain barrier integrity. Breach of blood vessel integrity is less likely once the vessels become accustomed to high pressures.     

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。     

The adrenergic innervation of pulmonary vasculature in the normal and pulmonary hypertensive rat

It would appear that susceptibility to chronic proliferative pulmonary hypertension in response to chronic alveolar hypoxia is most severe in species in which adrenergic innervation of pulmonary arteries is reduced or lacking. Intrapulmonary arteries of the rat have been reported to lack adrenergic innervation by some workers but not others. Since the rat develops severe proliferative pulmonary hypertension in response to prolonged alveolar hypoxia, the different divisions of the lung vasculature of Sprague-Dawley rats were thoroughly examined to determine the presence or absence of an adrenergic innervation. The degree of innervation in normal rats was compared with that of rats developing pulmonary hypertension. Both in normal and experimental pulmonary hypertensive rats the pulmonary arteries, all their branches and the small pulmonary veins with a smooth muscle media were found to be devoid of adrenergic innervation. In contrast, the cardiac-like muscle in the media of large pulmonary veins, the bronchial arteries and the vasa vasorum of larger vessels were richly innervated by adrenergic nerves. Thus the increase in medial smooth muscle which occurs in pulmonary arteries during chronic alveolar hypoxia is independent of a pre-existing adrenergic innervation or of such an innervation newly derived from that of adjacent vessels or structures. This is in contrast to systemic vessels where it has been suggested that increased adrenergic activity and density of innervation may augment hypertrophy of the media in hypertensive animals. Adrenergic nerves are suggested to have a protective action on pulmonary vessels.     

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.