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。     

新型脑白质病变动物模型及其脑小血管的病理学研究

目的建立一个新型的具有高血压及脑小血管病理改变的脑白质病变(white matter lesions,WMLs)动物模型。方法 13只雄性Sprague-Dawley大鼠,随机分为假手术组(n=6)与易卒中型肾血管性高血压-改良的2VO组(stroke-prone renovascular hypertensive rat-modified 2 vessel occlusion RHRSP/Modified 2VO)(n=7),RHRSP/Modified 2VO组先行双肾双夹术制作RHRSP模型,12周后间隔1周先后夹闭双侧颈总动脉。双肾双夹术后20周对大鼠进行水迷宫试验观察大鼠是否存在空间记忆功能的受损,组织病理学检测观察是否存在脑白质病变及相应的脑小血管病理学改变。结果双肾双夹术后12周,RHRSP/Modified 2VO组7只大鼠收缩压均大于180 mm Hg;水迷宫实验:RHRSP/Modified 2VO组的逃避潜伏期较假手术组明显升高(P0.05),穿越平台次数及原平台象限停留时间比较假手术组明显降低[(2.5±1.05 vs.5±1.67);(28.04%±14.13%vs.49.69%±13.12%)],差异具有统计学意义(P0.05);RHRSP/Modified 2VO组脑白质病变的分级明显高于假手术组(2.17±0.75 vs.0.33±0.52),差异具有统计学意义(P0.05),且RHRSP/Modified 2VO大鼠存在脑小血管的病理改变(小动脉管壁增厚、血脑屏障破坏及静脉胶原沉积)。结论 RHRSP/Modified 2VO是适用的WMLs动物模型,可用于探究WMLs的发病机制及治疗靶点。     

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。     

尼膜酮对蛛网膜下腔出血患者血浆内皮素和降钙素基因相关肽的影响

目的探讨血浆内皮素(ET)和降钙素基因相关肽水平(CGRP)在蛛网膜下腔出血病人急性期中的变化。方法采用放射免疫分析技术,在42例蛛网膜下腔出血病人的急性期测定血浆ET和CGRP含量,并与35例健康人员作比较。结果蛛网膜下腔出血病人血浆ET含量在尼膜酮治疗后有所下降(P<0.05),而CGRP的浓度升高(P<0.05)。结论血浆ET在蛛网膜下腔出血的急性期显著升高,并与脑损伤程度有关,提示神经肽参与出血性脑损伤的发生发展过程;尼膜酮可能对ET-1和CGRP有治疗作用。     

延髓左侧腹外侧神经血管压迫致高血压的动物实验研究

目的探讨神经源性高血压的发生机制。方法放免法测定动物模型建立前后其血浆中肾素活性、血管紧张素Ⅱ浓度;实验动物模型建立前后神经病理学与投射电镜检查。结果⑴高血压组犬术后4个阶段所记录动脉收缩压(SBP)、舒张压(DBP)、平均动脉压(MAP)及心率(HR)分别较术前均有明显升高(P<0.001);对照组犬模型建立前后SBP、DBP、MAP及HR等观察指标差异无统计学意义(P>0.05)。⑵对照组犬模型建立前、后PRA及ANGⅡ浓度变化均无统计学意义(P>0.05);高血压组犬模型建立后PRA及ANGⅡ浓度均较模型建立前有明显变化,统计学上有统计学意义(P<0.05)。⑶神经病理学及透射电镜检查示高血压组犬神经脱髓鞘等有异常表现。结论左侧延髓腹外侧Ⅸ、Ⅹ颅神经REZ动脉血管压迫所导致的高血压的发生与左侧延髓血管运动中枢对血压的调节失衡有关。     

盐酸法舒地尔对脑出血大鼠脑血管痉挛的作用研究

目的探讨盐酸法舒地尔(FH)对脑出血(ICH)大鼠脑血管痉挛的影响。方法 60只雄性Wistar大鼠随机分为4组:正常对照组、假手术组、脑出血+生理盐水(ICH+NS)组、脑出血+盐酸法舒地尔(ICH+FH)组,采用非抗凝自体动脉血注入右侧尾状核法建立ICH模型,建模12h后每日给予腹腔注射NS或FH(12mg·kg~(-1))。于1d、3d、7d及14d光镜下观察基底动脉形态学改变并采用医学专业图像分析软件测量基底动脉管腔面积及管壁厚度变化。结果 ICH+NS组在建模后1d及3d和ICH+FH组7d时基底动脉的管腔横截面积与血管横截面积之比均较正常对照组及假手术组明显降低,ICH+NS组在建模后1d、3d、7d和ICH+FH组7d时基底动脉管壁厚度与血管外径周长之比均较正常对照组及假手术组明显升高,差异均有统计学意义(P0.05);而ICH+FH组在建模后1d、3d基底动脉管腔横截面积与血管横截面积之比较ICH+NS组明显升高,1d及3d时基底动脉管壁厚度与血管外径周长之比较ICH+NS组明显降低,差异均有统计学意义(P0.05)。结论 ICH后可能发生脑血管痉挛,且FH可能减轻ICH后脑血管痉挛,从而缓解ICH后继发性缺血性脑损伤。     

亚低温治疗对重型颅脑损伤患者血浆内皮素的影响

目的探讨亚低温治疗重型颅脑损伤的临床疗效及其对血浆内皮素(ET)分泌的调控作用。 方法选取50例重型颅脑损伤患者,分为观察组(n=25)和对照组(n=25)。对照组给予常规治疗,观察组给予常规治疗联合亚低温治疗。比较两组血浆ET表达、颅内压(ICP)及临床预后。 结果治疗后第1~5天,观察组患者血浆ET均显著低于对照组,组间比较差异显著(P<0.05)。治疗后第1~5天,观察组患者ICP均显著低于对照组,组间比较差异显著(P<0.05)。观察组中预后良好7例、轻残8例、重残6例、植物生存2例、死亡2例;对照组预后良好3例、轻残4例、重残10例、植物生存3例、死亡5例,观察组预后情况明显优于对照组,组间比较差异显著(P<0.05)。 结论亚低温治疗的脑保护作用可能与抑制ET分泌,降低ICP有关。     

脑缺血后脑组织和血浆中内皮素的变化

建立兔大脑中动脉阻断(MCAO)脑缺血模型。将48只兔随机分为四组:C(正常对照和假手术对照组)和脑缺血 I_2、I_4、I_(24)组,每组12只,测脑 H_2O、Na~+、K~+、Ca~(2+)、内皮素(ET)和血浆 ET。结果示脑缺血侧脑皮质和血浆中 ET 含量显著高于对照组(P<0.001),且随时相递增(P<0.01),ET与脑 H_2O 含量之间呈显著正相关(P<0.05),提示 ET 可能参与脑缺血、脑水肿的发生发展。     

蛛网膜下腔出血后脑血管痉挛与血管活性物质的关系

目的 探讨蛛网膜下腔出血后脑血管痉挛与血管活性物质的关系。方法 测定52例蛛网膜下腔出血患者血浆血栓素B_2(thromboxane B_2,TXB_2)、6-酮-前列环素F1α(6-keto-prostaglandin,6-Keto)及血浆和脑脊液中血管紧张素转化酶(angiotensin converting enzyme,ACE)活性,同时通过经颅多普勒超声检查法(transcranial Doppler nltrasonography,TCD)观察蛛网膜下腔出血后脑血管平均血流速度(Vm)的变化,并与正常对照组进行比较。结果 蛛网膜下腔出血患者血浆TXB_2水平高于对照组(P<0.01),6-Keto水平低于对照组(P<0.05或P<0.01);发病后血浆ACE活性无明显改变,但脑脊液中ACE活性高于对照组(P<0.01);大脑中动脉平均血流速度于蛛网膜下腔出血后第4～5d的变化最为显著(P<0.01)。结论 蛛网膜下腔出血后患者血浆TXB_2、6-Keto与脑脊液ACE水平均发生明显变化,结合TCD检测结果,推测蛛网膜下腔出血后脑血管痉挛与血管活性物质水平有关。     

老年高血压伴抑郁患者血浆肾素-血管紧张素Ⅱ-醛固酮的研究

目的:探讨老年高血压合并抑郁患者血浆肾素-血管紧张素Ⅱ-醛固酮水平的变化与抑郁症、高血压病的关系。方法:原发性老年高血压病患者180例分为:高血压伴抑郁组(90例)、高血压组(90例),另设对照组(健康在校大学生90例),用放射免疫分析法测定血浆肾素-血管紧张素Ⅱ-醛固酮水平。结果:高血压伴抑郁组和高血压组血管紧张素Ⅱ均显著高于对照组(P<0.01);高血压伴抑郁组血管紧张素Ⅱ水平也显著高于高血压组(P<0.01)。高血压伴抑郁组和高血压组的肾素水平均显著低于对照组(分别P<0.05,P<0.01);高血压伴抑郁组肾素水平与高血压组比差异无统计学意义(P>0.05)。3组间血浆醛固酮水平无差异。高血压伴抑郁组的血浆血管紧张素Ⅱ水平与抑郁病程(r=0.412,P<0.01)和血压水平(r=0.369,P<0.01)呈一定正相关关系。结论:血管紧张素Ⅱ与老年高血压合并抑郁关系密切,血管紧张素Ⅱ可能参与了老年高血压合并抑郁的病理生理过程。     

电针对脑缺血大鼠神经黏蛋白mRNA表达与细胞超微结构的影响

目的观察电针对易卒中型肾血管性高血压大鼠(stroke prone renovascular hypertensive rats,RHRSP)脑缺血-再灌注后不同时间点神经黏蛋白mRNA(neurocan-mRNA)表达、细胞超微结构的影响。方法用环形银夹使SD大鼠的双侧肾动脉狭窄,制成RHRSP,再用线栓法制成一侧大脑中动脉闭塞(middle cerebral artery occlu-sion,MCAO)模型。运用原位杂交和电镜等技术观察电针对脑缺血2h后再灌注1、7、14、30d大鼠脑内神经黏蛋白-mRNA表达与细胞超微结构的干预作用,并与对照组比较。结果电针组脑缺血-再灌注7、14、30d大鼠脑缺血区周围及海马区neurocan-mRNA表达均低于同期对照组,差异有统计学意义(P<0.05);电针组神经元、血管壁等细胞超微结构的损伤较对照各组减轻。结论电针对RHRSP脑缺血-再灌注损伤的保护作用,可能与其下调神经抑制因子neurocan-mRNA表达、减轻细胞超微结构损害等机制有关。     

腹膜透析液添加尿激酶对尿毒症合并急性脑梗死患者治疗机理研究

目的探讨腹膜透析液添加尿激酶对尿毒症并发脑梗死患者血清超氧化物歧化酶(SOD)、丙二醛(MDA)、血浆内皮素(ET)及一氧化氮(NO)的影响。方法将健康体检者30人设为健康组,60例尿毒症并发脑梗死患者随机分为治疗组(30例)和观察组(30例),两组基础治疗相同,治疗组在观察组基础治疗上加用腹膜透析液添加尿激酶,治疗8w后观察两组患者超氧化物歧化酶、丙二醛、内皮素及一氧化氮的变化。用比色法测定健康组、观察组、治疗组血清MDA和SOD水平,用放射免疫法测定血浆ET的变化,NO采用硝酸还原法测定。结果与健康组比较,观察组、治疗组血清SOD活性降低(P<0.05),NO降低(P<0.05),MDA含量升高(P<0.05),血浆ET水平升高(P<0.01)。观察组虽能够降低血浆ET水平和升高NO,但未见SOD、MDA的变化,治疗组能够回升SOD活性,降低MDA含量,与健康组及观察组有明显差别(P<0.05,P<0.05),与观察组比较,治疗组在降低ET和升高NO方面疗效更为显著(P<0.01)。结论腹膜透析液添加尿激酶可能通过降低氧化应激反应,降低血浆ET和升高NO水平,对30例尿毒症并发脑梗死患者有治疗作用。     

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.     

大鼠大脑皮层梗死后丘脑继发性轴突变性

目的 探讨高血压大鼠大脑皮层梗死同侧丘脑腹后核（ventroposterior nucleus of the thalamus,VPN）继发性轴突变性的病理过程。方法 采用易卒中型肾血管性高血压大鼠（stroke-prone renovascular hypertensive rats,RHRSP）模型制备右侧大脑中动脉皮层支闭塞（middle cerebral artery occlusion,MCAO）模型,作为MCAO组。RHRSP模型仅暴露而不凝闭右侧大脑中动脉皮层支（middle cerebral artery,MCA）,作为假手术组。健康配对的成年大鼠,作为正常对照组。上述3组动物分别在术后1、2、4周3个时间点,行Bielschowsky氏嗜银染色及免疫组织化学染色检测梗死同侧丘脑腹后核βA4淀粉样前体蛋白（amyloid βA4 precursor protein,APP）、生长相关蛋白43（growth associated protein-43,GAP-43）和微管相关蛋白2（microtubule associated protein-2,MAP-2）的表达水平。结果 与同期假手术组相比,在梗死同侧丘脑腹后核,缺血4周时检测到嗜银染色的纤维束明显减少（P <0.05）;APP蛋白在缺血1周时表达开始增强并逐渐增高（P <0.05）,GAP-43蛋白、MAP-2蛋白的表达水平在缺血1～2周开始下降（P <0.05）并持续降低（P <0.05）。结论 轴突标志性蛋白的免疫组织化学检测方法敏感性高、能早期发现丘脑轴突的病理改变,与传统的嗜银染色方法结合,能较全面地评价VPN轴突变性的病理过程。本实验发现梗死同侧VPN的轴突变性是一个慢性进展性的过程。     

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。     

Delayed Decompressive Craniectomy Improves the Long-term Outcomes in Hypertensive Rats with Space-occupying Cerebral Infarction

Background and Purpose

No experimental data has been published on the long-term effects of decompressive craniotomy in hypertensive rats with space-occupying cerebral infarction. The aim of the present study was to investigate the efficacy of decompressive craniectomy in a middle cerebral artery occlusion (MCAO) model of hypertensive rats in a prolonged period.

Methods

Totally 92 stroke-prone renovascular hypertensive rats (RHRSP) were subjected to left MCAO by an endovascular occlusion technique. The decompressive craniectomy was performed on 26 RHRSP at 1 and 24 h after MCAO, respectively. Infarct volume, neurological performance, and mortality were evaluated at 1, 2, 4, and 8 weeks after MCAO.

Results

The mortality was reduced from 52.5% in controls to 7.7% and 23.1% in the rats underwent craniectomy at 1 and 24 h after MCAO, respectively (P < 0.05, respectively). All of the treated rats presented smaller infarct volume from 1 week to 8 weeks and better neurological performance at 4–8 weeks after MCAO compared to the controls (P < 0.05, respectively). The craniectomy at early stage was more effective than that at late stage in reducing infarct volume and improving neurological performances at 1 and 2 weeks (P < 0.05, respectively). However, there was no significant difference in infarct volume and neurological scores between the treated groups of rats at 4 and 8 weeks after MCAO (P > 0.05).

Conclusions

Although the early craniectomy is more effective than delayed craniectomy in improving short-term outcome, the latter has the similar beneficial effects as early craniectomy on long-term outcome in hypertensive rats with space-occupying cerebral infarction.     

环维黄杨星D对高血压大鼠脑缺血GAP-43 mRNA表达与细胞损伤的影响

目的观察中药单体环维黄杨星D(CVB-D)对易卒中型肾血管性高血压大鼠(RHRSP)脑缺血再灌注不同时间脑组织生长相关蛋白-43(GAP-43)mRNA表达与细胞超微结构损伤的影响。方法采用环形银夹使SD大鼠的双侧肾动脉狭窄,制成RHRSP,再用线栓法制成一侧大脑中动脉闭塞(MCAO)模型。用原位杂交等方法观察CVB-D对脑缺血2h后复流1d、7d、14d、30d不同时间点大鼠脑组织GAP-43mRNA表达、水含量、梗死面积百分率、行为学评分及细胞超微结构的干预作用。结果脑缺血2h复流后1d缺血区周围及海马可见GAP-43mRNA表达,7d明显增多至高峰,14d开始下降,30d时则明显减少,CVB-D治疗组在上述区域各时间点较对照组显著增加。脑缺血再灌注7d后,治疗组较对照组大鼠脑水含量及梗死面积显著降低,受损脑组织神经元和血管壁的超微结构亦明显改善。结论CVB-D对RHRSP缺血性脑细胞损伤有一定保护作用,其促进轴突的再生可能与上调脑组织GAP-43mRNA表达有关。     

The effects of endothelin antagonist BQ-610 on cerebral vascular wall following experimental subarachnoid hemorrhage and cerebral vasospasm

Abstract. Endothelin, a potent vasoconstrictor, has been found to increase in the cerebrospinal fluid and serum of patients following subarachnoid hemorrhage (SAH) and to play a major role in the development of cerebral vasospasm. The aim of this study is to investigate the role of endothelin-A antagonist BQ-610 in the experimentally performed cerebral vasospasm following SAH. Thirty New Zealand rabbits were divided into three groups (each n = 10): group A, control group; Group B, SAH group; Group C, treatment (endothelin antagonist BQ-610 treated) group. In the study, the rabbits developed vasospasm after injection of intracisternal autolog blood into the cisterna magna. After cerebral vasospasm development, in group C, endothelin antagonist BQ-610 was injected intracisternally. Morphometrically, basilar artery lumen was constricted 25% and 62% compared to the control group (group A) in the endothelin treated group (group C) and the endothelin untreated group (group B), respectively. Histopathological findings of the basilar artery wall confirmed the therapeutic effect of endothelin antagonist in vasospasm development. Endothelin-A receptor antagonist BQ-610 has a therapeutic effect in the cerebral vasospasm following experimentally performed subarachnoid hemorrhage when used intracisternally.     

易卒中型肾血管性高血压大鼠血浆CAM-1和P-选择素的动态观察

目的动态观察易卒中型肾血管性高血压大鼠（RHRSP）血浆ICAM-1和P-选择素的活性改变。方法双肾双夹法制作RHRSP模型,分别于术前及术后2、4、6、8、10、12、16周取血,酶联免疫吸附测定（ELISA）法检测ICAM-1和P-选择素含量。结果4周始RHRSP血中ICAM-1和P-选择素含量逐渐增高,明显高于正常对照组,且ICAM-1和P-选择素呈正相关,ICAM-1和P-选择素均与大鼠收缩压密切相关。结论血浆中ICAM-1和P-选择素含量升高提示梗死或出血的危险性增加,可作为脑卒中的预测指标之一。