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．     

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…

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ＲＨＲ高血压的形成     

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。     

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。     

自发性高血压大鼠下丘脑和血浆ET、CGRP含量变化的研究

本实验动态测定自发性高血压大鼠（ＳＨＲ）不同时期下丘脑和血浆ＥＴ、ＣＧＲＰ含量的变化以及其局部脑缺血后不同时期的改变。结果发现，ＳＨＲ３月龄和７月龄其下丘脑和血浆中的ＥＴ含量均明显高于同龄Ｗｉｓｔａｒ鼠（ＷＲ）（Ｐ＜０．０１），而ＣＧＲＰ含量均明显低于同龄ＷＲ（Ｐ＜０．０１）。局部脑缺血后２４小时，无论ＳＨＲ还是ＷＲ，其下丘脑和血浆ＥＴ和ＣＧＲＰ均比缺血前明显增高（均Ｐ＜０．０１）。缺血持续７天时，除ＳＨＲ下丘脑和血浆ＥＴ水平仍保持高水平外，其余均恢复正常。结果提示，高水平的ＥＴ含量和较低的ＣＧＲＰ含量可能与ＳＨＲ高血压的形成和发展有关     

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。     

大鼠急性脑缺血血浆及脑组织NO,ET1含量的变化

通过对大鼠急性脑缺血模型及假手术对照组血浆及脑组织一氧化氮（ＮＯ）、内皮素１（ＥＴ１）含量的测定，并观察脑缺血局部脑血流量及病理学改变。与对照组比较，模型组局部脑血流量降低，病理学改变加重，血浆中ＮＯ呈下降趋势，ＥＴ１水平明显升高；脑组织ＮＯ合成酶活性升高，ＮＯ及ＥＴ１含量明显升高。     

高血压对大鼠局灶性脑缺血再灌注损伤组织病理结构的影响

目的研究高血压对脑缺血性损伤的病理及其超微结构的影响。方法用线栓法将肾性高血压大鼠和正常大鼠制成局灶性脑缺血再灌注模型；TTC染色及图像分析系统测定局部脑缺血后不同时间的梗死灶体积．同时HE染色及透射电镜观察大鼠局灶脑缺血再灌注后及假手术组的组织病理及超微结构的变化。结果高血压大鼠与正常血压大鼠相比局部缺血再灌注在同等时间内梗死灶的面积较大，超微结构改变也较明显。结论高血压引起脑内微小动脉的改变．侧支循环减少．加重脑缺血损伤。     

脑出血病人脑血流量及红细胞变形性的变化

探讨脑出血病人脑血流量和红细胞变形性(ED)的变化.应用SPECT仪测定66例脑出血病人的局部脑血流量(rCBF),并同时采血测定红细胞变形指数.认为,病变侧rCBF明显低于对侧,其中内囊区出血rCBF比值下降最明显.其次是壳核出血,而丘脑出血下降最小;红细胞变形指数较正常对照组明显降低.提示:脑出血病人rCBF和ED降低参与脑出血的病理过程.     

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。     

兔MCAO后脑组织和血浆内皮素的变化

建立兔ＭＣＡＯ脑缺血模型。兔４８只随机分成４组：对照组Ｃ、脑缺血后２ｈ、４ｈ、２４ｈ组。用放免法测兔脑组织和血浆的内皮素含量。发现脑缺血后，缺血侧脑组织和血浆内皮素含量均显著高于对照组（Ｐ＜０．００１），且随缺血后时间的延长而递增（Ｐ＜０．０１）。内皮素与脑水含量之间呈显著正相关（Ｐ＜０．０５）。提示内皮素可能参与缺血脑损害并加重缺血后脑水肿。     

Concurrence of iris aneurysms and cerebral hemorrhage in hypertensive rabbits.

The development of miliary aneurysms of the iris is associated with the high risk of cerebral hemorrhage in rabbits with renal hypertension. The high-risk group of hypertensive rabbits in this series was characterized by the formation of iris aneurysms, and this group developed a striking proportion of hemorrhagic strokes (42.5%). In the low-risk group of hypertensive rabbits that did not develop aneurysms of the iris, only a low proportion of cerebral hemorrhages were found (11%). The development of iris aneurysms in rabbits was directly proportional to increments in level of blood pressure, and their rate of formation was very rapid. The formation of miliary aneurysms of the circular artery of the iris in hypertensive rabbits is likely related to the common embryologic origin and the morphologic similarity between perforating arteries of the brain and the principal arterial vessel of the iris.     

枸杞多糖对颅内动脉瘤大鼠NF-κB信号通路及血管内皮组织炎性损伤的影响

目的 探讨枸杞多糖(LBP)对颅内动脉瘤(IA)大鼠核蛋白因子-κB(NF-κB)蛋白通路及血管内皮组织炎性损伤的影响。方法 取SD雌性大鼠50只,采用切除双侧卵巢并结扎左侧颈总动脉及双侧肾动脉后支以构建IA模型,随机分为IA模型组、LBP低(5 mg/kg)、中(10 mg/kg)、高(20 mg/kg)剂量组,另取10只大鼠,只暴露卵巢、颈总动脉、双侧肾动脉后支,不进行摘除和结扎,作为对照组(Control组); 各组均于手术1周后,开始给药,Control组、IA模型组经灌胃给予生理盐水,LBP各剂量组灌胃给予相应剂量药物,1次/d,共给药30 d; 末次给药12 h后处死,取大鼠血液用酶联免疫吸附法(ELISA)检测血清炎性因子白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)及血管内皮损伤标志物血管内皮生长因子(VEGF)、血管内皮素(ET)水平; 分离取出大鼠脑动脉(Wills)环,在40倍显微镜下检查大脑动脉(Wills)环病理改变,并检测动脉瘤血管壁厚度及动脉瘤体积; 取脑动脉瘤血管组织,用苏木精-伊红染色(HE)检测动脉瘤血管组织病理变化; 蛋白免疫印迹法(Western blot)检测动脉瘤血管组织NF-κB,Toll样受体-4(TLR4)蛋白表达水平。结果 与Control组比较,IA模型组大鼠Willis环上凸起、管壁厚度和肿动脉瘤体积、动脉瘤内皮细胞空泡变性及炎性细胞浸润等病理损伤程度、血清IL-6,TNF-α,VEGF,ET水平、动脉瘤血管组织NF-κB和TLR4蛋白表达水平明显升高(P<0.05); 与IA模型组比较,LBP低、中、高剂量组大鼠Willis环上凸起、管壁厚度和动脉瘤体积、动脉瘤内皮细胞空泡变性及炎性细胞浸润等病理损伤程度、血清IL-6,TNF-α,VEGF,ET水平、动脉瘤血管组织NF-κB和TLR4蛋白表达水平明显降低(P<0.05),且LBP各剂量组上述指标水平呈剂量依赖性降低。结论 LBP可能通过抑制TLR4/NF-κB通路激活、降低炎症反应来减轻IA血管内皮组织损伤。     

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.     

Does methylmercury intoxication induce arteriosclerosis in humans? A pathological investigation of 22 autopsy cases in Niigata,Japan

Summary In order to clarify whether or not arterio-and/or arteriolosclerosis is induced or exacerbated in patients with methylmercury (Me-Hg) intoxication, the pathological features of arteries and arterioles in specific areas in 22 patients and 36 control subjects were examined qualitatively and quantitatively. Vessels investigated were: (1) small arteries and arterioles in the subarachnoid space and cortex of the postcentral gyrus, transverse temporal gyrus, first visual area and cerebellar vermis, as well as the myocardium and renal cortex; (2) the lateral striate artery; (3) the internal carotid, anterior, middle and posterior cerebral, basilar and vertebral arteries, as well as the coronary and renal arteries; and (4) the aorta. The arteriosclerotic changes observed in the patients with Me-Hg intoxication were indistinguishable both qualitatively and quantitatively from those of controls. The results indicate that Me-Hg intoxication does not induce or exacerbate sclerotic changes in arteries and arterioles. Thus, the peculiar neurological symptoms and neuropathological features of Me-Hg intoxication are thought to be induced not by ischemia but by selective primary degeneration of the neurons in specific regions.Supported in part by The Japan Environmental Agency     

An experimental study on cerebral arteriosclerosis

The experimental study suggested that it would be difficult to induce atherosclerosis in the cerebral arteries. Although the atherosclerotic lesions on the aortas were evident in the experimental rabbits of the hypertension plus hypercholesterolemia group, evidence of early atherosclerosis was found on the intracranial small arteries in only three out of the 10 rabbits of this group. Under the microscope widespread thickening and contraction were seen on almost all the small cerebral and cerebral parenchymal arteries. Hyaline degeneration could be seen in some of the arteries. Most of the cerebral parenchymal capillary endothelia were swollen and some of these cells contained lipid drops. All of these pathological changes could not be found in the authors earlier experiment in the group of the rabbits without hypertension. It was, therefore, surmised that both hypertension and hyperlipidemia would be two of the important factors in inducing the lesions in the cerebral arteries, but although such factors would be coordinative, hypertension might be more important in the process of damaging the cerebral arteries and leading to their degenerative changes.     

急性脑血管病患者红细胞流变学研究

对３５例急性脑血管病（ＡＣＶＤ）患者，分脑出血（ＣＨ）组及脑梗塞（ＣＩ）组，分别检测红细胞各实验参数、红细胞变形能力（ＲＣＤ）及红细胞聚集（ＥＡＧ），并设立３２例对照。结果显示红细胞各实验参数有不同程度改变，部分具统计学意义。脑出血组ＲＣＤ及ＥＡＧ与对照组比较无统计学意义，而脑梗塞组ＲＣＤ各切应力下均低于对照组（Ｐ＜０．０１），ＥＡＧ高于正常对照（Ｐ＜０．００１）。ＣＩ组红细胞各参数间有一定相关性，ＣＨ组相关不明显。对ＲＣＤ改变机理及临床意义进行了初探。     

血浆多种神经肽与缺血性脑血管病相关性研究

目的 :探讨血浆多种神经肽在缺血性脑血管病中的作用。方法 :采用放射免疫法检测 112例不同类型缺血性脑血管病患者血浆降钙素基因相关肽 (CGRP)、内皮素 (ET)、心房利钠肽 (ANP)、神经肽 Y(NPY)、神经降压肽(NT)水平。结果 :急性脑梗死 CGRP、 NT较对照组降低 (P<0 .0 5 ) ,ET、 ANP、 NPY均较对照组升高 (P<0 .0 1) ,病情重者较轻者变化更显著 (P<0 .0 1) ,椎动脉供血不足组 CGRP、 ET、 ANP、 NPY均较对照组升高 (P<0 .0 1) ,脑动脉硬化组 ET较对照组升高 ,NT较对照组降低 (P<0 .0 5 ) ,其他神经肽变化不显著。结论 :神经肽参与了缺血性脑血管病病理生理过程 ,其改变可作为早期判断缺血性脑血管病严重程度指标之一