肾性高血压大鼠脑血管病理及发病机制的研究

目的　探讨肾性高血压大鼠高血压形成的可能机制 ,观察脑内大动脉和血液流变学改变的特点。方法　比较 14周后的肾性高血压大鼠 (实验组 )与对照组大脑中动脉和基底动脉的血管变化 ,并检测血液中降钙素基因相关肽 (CGRP)、内皮素 (ET) ,观察血液流变学变化及脑组织c sis基因表达量。结果　实验组大鼠的大脑中动脉平滑肌增厚、血管横切面积、中层面积、管腔面积增大 ;基底动脉平滑肌增厚、中层面积增大 ,血管横切面积、管腔面积变窄。血液粘度增高 ,血浆内皮素 (ET)、降钙素基因相关肽 (CGRP)水平、c sis基因表达量与对照组有极显著差异。结论　肾动脉狭窄可引起大鼠大脑中动脉、基底动脉血管重构 ,血液粘度增高以及血浆ET、CGRP合成、分泌不平衡 ;c sis基因表达增多等这些变化都可能是导致动脉硬化的重要因素。     

高血压脑动脉硬化大鼠内皮素及一氧化氮变化的研究

目的　探讨高血压脑动脉硬化时（ Ｅ Ｔ 与 Ｎ Ｏ）变化的特点以及 Ｅ Ｔ、 Ｎ Ｏ 对脑动脉硬化的影响。方法　用双肾双夹法复制出高血压 Ｓ Ｄ 大鼠，持续 １４ 周比较实验组与对照组大脑中动脉及基底动脉的平滑肌厚度，以及测定 Ｅ Ｔ、 Ｎ Ｏ 在血浆中的含量。结果　肾血管狭窄后血压持续升高，至 １４ 周时血压至 ２７．５±３３．５ｋ Ｐａ。大鼠的大脑中动脉及基底动脉平滑肌增厚、管腔狭窄，血管壁有重构。血浆 Ｅ Ｔ 水平明显高于对照组（ Ｐ＜ ０．０１），血浆 Ｎ Ｏ 水平与对照组无显著性差异（ Ｐ＞ ０．０５）。结论　肾脏缺血可引起 Ｅ Ｔ 和 Ｎ Ｏ 合成、分泌明显的不平衡， Ｅ Ｔ 分泌增多、 Ｎ Ｏ 相对分泌不足。这种变化可能是致使长期高血压、脑血管平滑肌增厚及脑动脉硬化的重要因素。     

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     

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.     

局灶性脑梗死模型大鼠相对体质量、Bederson评分与梗死类型的鉴别

背景：采用MCAO法制作大鼠脑缺血模型时,通过分析Bederson评分结果并不能完全可靠的诊断皮质下梗死。 目的：对SD大鼠皮质梗死和皮质下基底核区梗死在不同时间点的体质量与Bederson评分结果进行比较。 方法：参照Zea Longa的线栓造模方法制作大脑中动脉闭塞模型SD大鼠,栓塞100 min后拔出线栓。术后将大鼠进行磁共振成像扫描,根据有无梗死灶及梗死部位的不同将大鼠分为：皮质下基底核区梗死组(n=13)、皮质梗死组(n=25)、未出现梗死组(n=10)。对3组大鼠大脑中动脉闭塞后7周内的体质量与Bederson评分结果进行监测。 结果与结论 皮质下梗死组与无梗死组在各时间点大鼠相对体质量相比无显著性意义(P > 0.05)。皮质梗死组大鼠的相对体质量在大脑中动脉闭塞后2周内明显小于皮质下梗死组,在大脑中动脉闭塞后3周内明显小于无梗死组(P < 0.05)。皮质下梗死组大鼠造模后第1天Bederson评分结果与皮质梗死组相比差异无显著性意义,但都明显高于无梗死组(P < 0.05)。提示可结合大鼠大脑中动脉闭塞后第1天的相对体质量与Bederson评分结果对大鼠的梗死类型进行鉴别。     

重视腔隙性脑卒中的诊断

腔隙性脑卒中(lacunarstroke)系指大脑半球深部和脑干等中线部位,由血管直径100～400μm的穿支动脉梗死所引起的,梗死病灶为0.5～15.0mm3的脑梗死。大多由大脑前、大脑中、大脑后、前脉络膜动脉和基底动脉的穿支动脉梗死所引起。高血压和糖尿病是其主要原因,特别是高血压尤为重     

芦荟大黄素对易卒中型肾血管性高血压大鼠大脑中动脉重塑的影响

目的观察芦荟大黄素对易卒中型肾血管性高血压大鼠（RHRSP）大脑中动脉结构改变的影响。方法取造模成功的36只RHRSP大鼠随机分成3组：芦荟大黄素低剂量治疗组、高剂量治疗组和高血压组，另取10只作为假手术对照组（除不上银夹外，其余措施同高血压模型组）。测量收缩压（SBP）和血浆中ET水平。血管平滑肌细胞经α-平滑肌肌动蛋白（α-SM-actin）免疫组化染色后，应用计算机图像分析测量大脑中动脉血管外径、中膜厚度、管腔内径、壁腔比和中膜平滑肌面积。结果低剂量治疗组血浆ET水平显著低于高血压组（P〈0．05），而高剂量治疗组则稍低（P〉0．05）。镜下观察发现低剂量治疗组血管形态损害比高血压组轻，而高剂量治疗组则无减轻甚至更重。低剂量治疗组血管外径、管腔内径、中膜厚度均大于高血压组（P〈0．05），壁腔比则小于高血压组（P〈0．05）。低剂量治疗组中膜平滑肌面积比高血压组大（P〉0．05），但在高剂量治疗组反而缩小（P〉0．05）。结论低剂量芦荟大黄素可降低RHRSP血浆ET水平，改善血管内皮功能，具有一定的改善血管重塑的作用。     

中药复健片对大脑中动脉闭塞大鼠脑多唾液酸-神经细胞黏附分子表达的影响

目的观察中药复方复健片对大脑中动脉闭塞模型大鼠脑内多唾液酸-神经细胞黏附分子(PSA-NCAM)的影响,探讨其促进神经发生的作用机制。方法60只Wistar大鼠随机分为药物组、模型组、假手术组,每组20只。用Tamura等方法制备大脑中动脉闭塞大鼠模型,于造模成功后6 h药物组按体重9 g/kg经灌胃给予复健片水溶液,余两组分别经灌胃给予同等量生理盐水(NS),1次/d,共7 d。用免疫组化法观察大脑中动脉闭塞模型大鼠脑内PSA-NCAM的表达,并对切片进行图像分析,测定染色平均灰度。结果56只大鼠纳入结果分析。给药1周后大鼠脑内PSA-NCAM染色平均灰度药物组为100.10±2.28,模型组为128.65±1.12,假手术组为140.20±8.68。药物组、模型组与假手术组组间比较差异有统计学意义(P<0.01),药物组与模型组比较差异有统计学意义(P<0.01)。结论复健片可显著增强大脑中动脉闭塞大鼠脑内PSA-NCAM的表达,从而促进缺血性脑卒中神经的发生。     

肾血管性高血压大鼠脑动脉瘤模型的建立及发生机制初步探讨

目的 :探讨采用易卒中型肾血管性高血压大鼠建立脑动脉瘤模型。方法 :建立大鼠肾血管性高血压模型 ,再电凝切断左侧颈总动脉 ,然后用光镜和电镜观察右侧大脑前动脉和嗅动脉分叉处及附近的组织学改变。结果 :实验组在 2 0 /2 3只大鼠中可见瘤前、早期及进展期的动脉瘤改变 ,与人类囊状动脉瘤的病理改变相似。结论 :结扎一侧颈总动脉造成血流动力学改变的易卒中型肾血管性高血压大鼠可以作为较理想的脑动脉瘤模型。     

脑动脉粥样硬化模型大鼠大脑中动脉的蠕变

背景：蠕变是生物材料黏弹性固体的表现形式之一,脑动脉硬化和脑出血的防治有必要了解脑动脉硬化大脑中动脉的蠕变力学特性。 目的：比较正常和动脉粥样硬化动物模型大脑中动脉的蠕变力学特性,确定动脉粥样硬化对大脑中动脉蠕变特性的影响。 方法：SD雄性大鼠随机分为两组,模型组肌注维生素D3+尼古丁灌胃+高脂饮食制备动脉粥样硬化模型,对照组正常饮食,4周后处死大鼠取大脑中动脉为标本试件。在日本岛津电子万能试验机上对正常和动脉粥样硬化动脉标本试样进行蠕变实验。蠕变实验的应力增加速度为0.01 MPa/s。设定实验时间为7 200 s,采集100个数,以一元线性回归分析的方法处理实验数据,记录蠕变曲线和数据,以及应变与时间的变化规律。 结果与结论：正常和动脉粥样硬化大鼠大脑中动脉蠕变最初600 s变化较快,之后应变缓慢下降,正常动脉标本7 200 s蠕变量高于动脉粥样硬化动脉标本(50.38%,48.26%,P < 0.05)。说明正常和动脉粥样硬化大鼠大脑中动脉具有不同的蠕变力学特性,提示蠕变曲线是以指数关系变化的,动脉粥样硬化对大脑中动脉蠕变特性具有一定影响。     

A new clinically relevant model for intracranial atherosclerosis in rats

Introduction: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and, in particular, has been implicated as a leading cause of recurrent ischemic stroke. We developed a new rat model to study intracranial atherosclerosis.

Methods: Twelve-week-old male Sprague-Dawley rats were divided into a control (on a maintain diet) and a high-cholesterol group (on a daily 1% cholesterol diet) for up to 6 weeks. During the first two weeks, NG-nitro-L-arginine methylester (L-NAME, 3 mg/mL) was added to the drinking water in the high-cholesterol group to induce intimal changes making the rats susceptible to atherosclerosis. Blood lipids, including low-density lipoprotein (LDL), cholesterol (CHO), triglycerides (TG), and high-density lipoprotein (HDL), were measured after 3 and 6 weeks. Histological sections of the brains, including internal carotid artery (ICA), middle cerebral artery (MCA), and basilar artery (BA), were prepared to study intracranial artery morphometry and intimal thickening. The levels of CD68, an inflammatory marker, within the vessel walls as determined by immunohistochemistry were also measured.

Results: The high-cholesterol diet increased the levels of classic blood markers of atherosclerosis, LDL, CHO, and TG as well as decreased HDL, which became progressively more intensive with time. Rats showed increased intimal thickening in the ICA, MCA, and BA. This protocol also increased the levels of CD68 immunoreactivity within the vessel walls.

Conclusions: A rat model of intracranial atherosclerosis was effectively developed by high-cholesterol diet and L-NAME administration. This clinically relevant model would be beneficial for studying ICAS.     

Corticofugal axonal degeneration in rats after middle cerebral artery occlusion

We used the Fink-Heimer method to study degenerating corticofugal axons after unilateral middle cerebral artery occlusion in 14 adult male Long-Evans hooded rats. Axonal degeneration in the pyramidal tracts was prominent at 1-3 weeks, manifesting in well-defined silver-impregnated axonal bundles coursing from the internal capsule to the pyramids and crossing completely to the contralateral spinal cord. In half of eight rats examined at 1-3 weeks, the cortical infarct included the forelimb region of the sensorimotor cortex, and degenerating corticospinal axons could be traced to the lower cervical segments; in rats with involvement of the hindlimb cortical area as well, axonal degeneration extended to the lumbosacral segments. Terminal degeneration products were present in the forebrain, midbrain, and brainstem within 2 days after arterial occlusion; the number of degenerating terminals peaked at 7 days and decreased gradually thereafter up to 6 weeks. Dense terminal degeneration was observed in the trigeminal nuclear complex of all seven rats studied at 2 and 7 days. In these seven rats, five had small cortical infarcts, and silver-impregnated terminals were observed in the lateral reticular formation; in two rats with large cortical lesions, terminal degeneration was prominent in the medial reticular formation as well. We conclude that infarcts produced by middle cerebral artery occlusion cause axonal degeneration in the brainstem and spinal cord. The Fink-Heimer method may be useful for evaluating the rat middle cerebral artery occlusion model.     

Behavioral changes after focal cerebral ischemia by left middle cerebral artery occlusion in rats

Behavioral changes after occlusion of the left middle cerebral artery (MCA) in rats were investigated for 16 weeks. Impairment of motor coordination and incidence of neurological deficits including hemiplegia and abnormal posture were present for the first 2 and 4 weeks after MCA occlusion, respectively. Learning behavior in one-trial passive avoidance task was disturbed for the entire 16-week period when rats were trained at days 3 after MCA occlusion. Reacquisition was also impaired when rats were retrained on 8 weeks after MCA occlusion. Except for synchronized EEG at days 2 after MCA occlusion, significant changes in spontaneous movement and EEG were not observed in the MCA-occluded group. These results suggest that this rat model of MCA-occlusion is useful for quantitatively measuring functional changes in chronic phase of focal cerebral ischemia.     

Effect of western and high fat diets on memory and cholinergic measures in the rat

Recent evidence shows an association between obesity and cognitive decline. The present study aimed to determine whether a very high fat (60%) or western diet can affect working or spatial memory in rats and whether the diet-induced cognitive impairment is linked to the level of acetylcholine in the brain. Three groups of male Long Evans rats were fed either chow, western diet (21% fat, 0.15% cholesterol) or a high fat diet (60% fat) for 12 weeks (n=12 per group). Body weight, food intake and blood pressure were measured weekly. Behavioural testing, novel object recognition and Y-maze were carried out at 12 weeks. At the end of the study brain choline acetyltransferase and acetylcholinesterase levels were estimated. Results showed that consumption of a western diet for twelve weeks impaired a rat's spatial memory (p<0.05), and increased body weight, calorie intake, blood pressure and triglyceride levels. Conversely our high fat diet also impaired spatial memory (p<0.05) but this effect was independent of the rat's body weight or blood pressure. No significant changes in brain acetylcholine markers were observed. In conclusion, diets with higher fat content impaired hippocampal-dependant memory, even when hypertension and obesity are absent; however the mechanism is still unclear.     

2型糖尿病对鼠缺血性卒中的影响

目的 研究2型糖尿病大鼠诱导血管内皮生长因子(VEGF)和血管增生作用及其在大脑中动脉局灶性脑缺血后对梗死体积、梗死后出血的影响.方法 诱导制备2型糖尿病大鼠,糖尿病大鼠与正常血糖鼠均采用线栓法制备大脑中动脉局灶性脑缺血模型.应用墨汁灌注脑血管法观察脑内血管,2,3,5-三苯四氮唑(TTC)染色法检测梗死体积,免疫组织化学方法 检测VEGF与CD34的表达.结果 墨汁灌注脑血管后在糖尿病组可见细小血管明显增生.TTC染色见糖尿病组梗死局限在皮质下,成蚕豆样,正常血糖组梗死相对弥散,广泛累及皮质,且糖尿病组梗死体积[(80.07±11.21)mm3]明显小于正常血糖组[(98.91±14.86)mm3],差异具有统计学意义(t=2.48,P=0.0326).糖尿病组可见明确的梗死后出血.免疫组织化学结果 显示VEGF与CD34的表达在糖尿病组明显高于正常血糖组,且差异均具有统计学意义.结论 糖尿病脑缺血性梗死后VEGF与CD34表达高于正常血糖组.糖尿病可明显诱导脑血管扭曲、重构及新生.这些病理性血管在脑缺血后可能会减小梗死体积但加重梗死后出血而影响预后.

Abstract：

Objective To study the function of vascular endothelial growth factor (VEGF) in type 2 diabetes model rats and its effect on focal cerebral ischemia induced by middle cerebral artery occlusion in these rats. Methods Focal cerebral ischemia was induced by middle cerebral artery occlusion for 6 hours in type 2 diabetes rats and normal control rats.Blood vessels morphology was examined by ink perfusion,infarct size was measured by TTC and expression of VEGF and CD34 were evaluated by immunohistochemistry staining. Results Ink perfusion revealed increased number of small vessels in type 2 diabetes rats. Infarct size was significantly smaller in type 2 diabetes rats ( ( 80. 07 ± 11.21 ) mm3 ) than that in normal controls ((98. 91 ± 14. 86) mm3,t = 2.48,P = 0. 0326). There were more hemorrhage lesions in the ischemic hemisphere in type 2 diabetes rats when comparing with the controls. VEGF and CD34 showed significantly higher expression in type 2 diabetes rats than in normal controls. Conclusions High expression of VEGF and CD34 are found in type 2 diabetes rats after middle cerebral artery occlusion. There is cerebrolvascular remodeling in diabetes rats. While this diabetes-induced remodeling appears to prevent infarct expansion,the changes also increase the risk of hemorrhagic transformation. The latter may result in poor prognosis.     

胰岛素抵抗大鼠血糖正常阶段颈动脉内皮细胞结构改变及可能机制

目的:观察胰岛素抵抗(IR)大鼠血糖正常阶段颈动脉内皮细胞超微结构病理改变。方法:普通饲料喂养的SD大鼠为正常对照,高脂饲料喂养SD大鼠6周复制IR模型。透射电镜观察颈动脉内皮超微结构;应用钳夹法评价大鼠的胰岛素敏感性;酶联免疫方法测定甘油三酯(TG)、胆固醇(TC)、高密度脂蛋白胆固醇(HDL)、低密度脂蛋白胆固醇(LDL)、空腹胰岛素(FIN)、游离脂肪酸(FFA)。结果:IR大鼠颈动脉电镜下可见部分内皮细胞和内皮下结构的病理性改变。IR大鼠实验结束时FBG及PBG2h与正常对照组比较无显著差异(P>0.05);与正常对照组相比IR大鼠血浆FINS、TG、TC、FFA水平明显高于正常对照组(P<0.05);胰岛素敏感性指数(ISI)显著降低(P<0.05);两组高密度脂蛋白(HDL)及低密度蛋白(LDL)水平比较差异无显著性(P>0.05)。结论:结论:高脂膳食诱发的IR大鼠在血糖正常阶段已存在颈动脉内皮超微结构的病理性改变,高胰岛素血症和脂代谢紊乱在内皮损害中可能发挥了重要作用。     

Soy protein diet increases skilled forelimb reaching function after stroke in rats

Stroke is a leading cause of lasting disability. Dietary strategies aimed at increasing post-stroke outcomes are lifestyle alterations which could be easily implemented by people at risk of occlusive stroke. Soy diets have been demonstrated to provide some benefits in the short term following stroke, but longer time periods have not been studied. Further, carefully defined diets containing soy protein isolates have not been investigated. In the current study, male Long Evans Hooded rats were fed semi-purified diets containing either sodium caseinate or soy protein isolate. Rats were trained to perform the skilled forelimb reaching task and subsequently underwent unilateral middle cerebral artery occlusion (MCAO) to induce a stroke lesion. After stroke, rats remained on the same diet and were tested daily for a period of 8 weeks to observe their performance on the skilled forelimb reaching task. In the first week following stroke, rats receiving the soy protein-containing diet (SP) demonstrated less severe reaching deficits than rats fed the Na caseinate-containing diet (CAS) (p<0.05). These results suggest that a soy protein-based diet provides significant protection from neurological damage following MCAO stroke in rats.     

Effects of a saturated fat and high cholesterol diet on memory and hippocampal morphology in the middle-aged rat

Diets rich in cholesterol and/or saturated fats have been shown to be detrimental to cognitive performance. Therefore, we fed a cholesterol (2%) and saturated fat (hydrogenated coconut oil, Sat Fat 10%) diet to 16-month old rats for 8 weeks to explore the effects on the working memory performance of middle-aged rats. Lipid profiles revealed elevated plasma triglycerides, total cholesterol, HDL, and LDL for the Sat-Fat group as compared to an iso-caloric control diet (12% soybean oil). Weight gain and food consumption were similar in both groups. Sat-Fat treated rats committed more working memory errors in the water radial arm maze, especially at higher memory loads. Cholesterol, amyloid-beta peptide of 40 (Abeta40) or 42 (Abeta42) residues, and nerve growth factor in cortical regions was unaffected, but hippocampal Map-2 staining was reduced in rats fed a Sat-Fat diet, indicating a loss of dendritic integrity. Map-2 reduction correlated with memory errors. Microglial activation, indicating inflammation and/or gliosis, was also observed in the hippocampus of Sat-Fat fed rats. These data suggest that saturated fat, hydrogenated fat and cholesterol can profoundly impair memory and hippocampal morphology.