单胺类神经递质和神经肽Y在老龄大鼠脑缺血再灌注心脏组织损伤中的意义

目的 从多巴胺（DA）、去甲肾上腺素（NE）、肾上腺素（E）、神经肽Y（NPY）方面揭示脑缺血心肌损伤的机制。方法 观察青年（5－6月龄）和老龄（20月龄以上）大鼠全脑缺血心肌损伤乳酸脱氢酶（LDH）、肌酸磷酸激酶（CPK）活性及NPY、DA、NE、E的含量。结果 青年模型组血清中CPK和LDH水平明显高于青年对照组和老龄模型组，老龄模型组高于老龄对照组。青年模型组和老龄模型组血中NE分别高于青年和老龄对照组；老龄模型组血中NE、E水平和下丘脑NE水平高于青年模型组，老龄模型组下丘脑中NE和E水平低于老龄对照组。脑组织中NPY老龄对照组低于青年对照组和老龄模型组。结论 在鼠脑缺血再灌注心肌损伤与交感－肾上腺系统兴奋性增强有关，老龄大鼠尤为明显。     

脑缺血再灌注心肌损伤老龄大鼠神经肽的变化

目的 从内皮素（ET）,降钙素基因相关肽（CGRP）,神经肽Y（NPY）,神经降压素（NT（的变化方面研究老龄大鼠脑缺血再灌注心肌损伤的机制。方法 青年（5月龄）和老龄（20月龄以上（大鼠均为分为模型组和正常对照组,观察大鼠全脑缺血30min 再灌注60 min后心肌组织病理形态和血浆,脑组织中ET,CGRP,NPY含量。结果 脑缺血再灌注心肌组织出现明显的病理改变,老龄大鼠较青年大鼠严重,青年对照组和青年模型组,老龄对照组脑组织中NPY低于青年对照组和老龄西药组,结论 脑缺血再灌注心肌损伤与以ET占优势的CGRP与ET的平衡失调有关,由于老龄大鼠ET与CGRP间平衡失调和NPY的增龄变化使脑缺血再灌注后这些病理改变较青年大鼠更为明显。     

白果内酯对高血糖大鼠脑缺血再灌注损伤的保护作用

目的 观察白果内酯对高血糖大鼠脑缺血再灌注损伤的保护作用及其可能机制.方法 采用50%的葡萄糖溶液腹腔注射(6 ml/kg)建立急性高血糖模型.采用线栓法建立大鼠脑缺血再灌注模型,按随机数字表方法将40只大鼠分为高血糖假手术组(假手术组),高血糖+缺血再灌注损伤组(模型组),高血糖+缺血再灌注损伤+白果内酯组(白果内酯组),白果内酯分三个剂量组(2.5,5,10 mg/kg),每组各8只.白果内酯组于术前3 d连续给予白果内酯腹腔注射,术前1 h再给予腹腔注射1次.脑缺血2 h,再灌注24 h后行神经功能缺损评分、脑梗死体积及脑含水量测定,同时测定脑组织中水通道蛋白-4(AQP4)mRNA的表达,超氧化物歧化酶(SOD)的活力,计算脑组织中丙二醛(MDA)的含量及去甲肾上腺素(NE)、多巴胺(DA)和5-羟色胺(5-HT)的表达.结果 白果内酯(5,10 mg/kg)组大鼠与模型组相比,神经功能缺损评分下降,脑梗死体积缩小,脑含水量降低,缺血侧脑组织中AQP4 mRNA的表达下调,SOD活力提高,MDA含量减低,NE、DA及5-HT的含量增加,差异均有统计学意义(P<0.05).结论 白果内酯对高血糖条件下的局灶性脑缺血再灌注损伤具有一定的保护作用.     

柴胡对肝郁证大鼠脑内单胺类神经递质的影响

目的探索柴胡对肝郁证大鼠中枢神经递质的作用。方法利用中医证候模型,研究柴胡对单胺类神经递质的作用。结果肝郁证模型组大鼠脑内去甲肾上腺素(NE)与多巴胺(DA)水平与对照组比较下降明显(P<0.05),肝郁证模型加逍遥散组大鼠脑内NE与DA水平与对照组比较差异无统计学意义(P>0.05),肝郁证模型加柴胡组大鼠脑内NE与DA水平与对照组比较差异无统计学意义(P>0.05)。结论肝郁证大鼠脑内NE与DA水平明显降低,柴胡舒肝解郁,有增加肝郁证大鼠脑内NE、DA神经递质的作用。     

全脑缺血后海马区单胺类神经递质的变化

目的观察全脑缺血后大鼠海马区单胺类神经递质的变化规律,探讨其在缺血后迟发性神经元死亡中的作用。方法建立大鼠全脑缺血再灌注模型,观察全脑缺血再灌注后酪氨酸羟化酶(TH)、多巴胺-β-羟化酶(DβH)的表达并对海马区去甲肾上腺素(NE)、肾上腺素、多巴胺、5-羟色胺(5-HT)和单胺类神经递质代谢产物高香草酸(HVA)、5-羟吲哚乙酸(5-H IAA)的含量进行测定。结果对照组TH及DβH呈阴性表达。全脑缺血再灌注后1 d,3 d缺血组海马CA1区神经元TH及DβH表达阴性。5 d后神经元TH及DβH呈阳性表达;全脑缺血再灌注后6 h,缺血组海马区单胺类神经递质含量显著上升,NE、肾上腺素、多巴胺及5-HT分别为对照组的232.5%、347.3%、336.1%和210.1%,1 d后开始回落,3 d已明显低于对照组,5 d后又有回升并接近对照组;缺血组,海马区单胺类神经递质的代谢产物HVA、5-H IAA含量于全脑缺血再灌注后6 h开始上升,1 d依然保持较高的水平,至3 d回落,5 d接近对照组。结论全脑缺血再灌注后早期海马区单胺类神经递质含量显著上升;单胺类神经递质含量显著上升可能是导致迟发性神经元死亡的主要因素之一。     

阿司匹林对大鼠局灶性脑缺血再灌注损伤中血NO、ET、TNF含量的影响

目的探讨阿司匹林对大鼠局灶性脑缺血再灌注损伤中血一氧化氮(NO)、内皮素(ET)、肿瘤坏死因子(TNF)含量的影响.方法将实验动物随机分为阿司匹林组、模型组、假手术组、对照组.阿司匹林组予阿司匹林连续灌胃、其他3组予生理盐水连续灌胃20天后,采用颈内动脉线栓法造成大鼠大脑中动脉缺血再灌注模型,应用荧光分光光度法和放射免疫分析法观察4组血NO、ET、TNF含量的变化.结果假手术组血NO、ET、TNF与对照组比较无显著性差异(P>0.05);与假手术组比较,模型组NO显著下降(P<0.01),ET、TNF明显升高(均P<0.05);与模型组比较,阿司匹林组NO明显升高 (P<0.05),ET、TNF明显降低(均P<0.05).结论阿司匹林对大鼠局灶性脑缺血再灌注损伤具有显著的保护作用,其机制可能与血N0含量升高及ET、TNF降低有关.     

老龄大鼠脑缺血再灌注血脑屏障损伤的变化及意义

目的研究老龄大鼠脑缺血再灌注（I／R）血脑屏障（BBB）损伤特点。方法采用大脑中动脉栓塞法复制局灶性脑缺血模型，随机分组，观察脑组织含水量、病理变化、免疫球蛋白（IgG）。结果随着再灌注时间的延长，BBB损伤逐渐加重，含水量增加和IgG漏出以I／R24h、3d显著；模型组含水量（I／R 12h～6d）较假手术组升高；青年模型（I／R12h～6d）和老龄模型（I／R 6h～6d）IgG漏出分别较青年和老龄脑缺血3h组增加；老龄模型组（I／R 12h～I／R6d）IgG的漏出高于同时间青年模型组。结论脑水肿和BBB损伤随着再灌注时间的延长而加重，IgG漏出老年较青年明显，血脑屏障的增龄变化可能是其机制之一。     

密闭舱室内亚致死性爆炸伤大鼠额叶皮质及血浆内单胺类神经递质的变化对大鼠旷场行为的影响

目的: 观察密闭舱室内亚致死剂量爆炸伤大鼠额叶皮质及血浆内单胺神经递质的变化对大鼠旷场行为的影响.方法:采用密闭舱室内亚致死剂量爆炸伤的大鼠模型,高效液相色谱电化学法分析大鼠血浆、额叶皮质内5-羟色胺(5-HT),多巴胺(DA),肾上腺素(E).去甲肾上腺素(NE)含量的变化,用旷场行为观察箱观察大鼠旷场行为.结果: 舱内亚致死剂量爆炸伤大鼠额叶皮质内NE,E含量较对照组明显升高(P<0.05),DA含量明显降低(P<0.05),5-HT的含量在爆炸后48 h达高峰,随后出现下降,密闭舱室内亚致死剂量爆炸后大鼠旷场行为较对照组明显减少(P<0.05).结论: 舱内爆炸后大鼠的兴奋性明显下降;大鼠旷场行为与舱内爆炸后额叶皮质E浓度呈负相关(r=-0.987,P<0.05),与5-HT浓度呈正相关(r=0.952,P<0.05),大鼠旷场行为与血浆内E浓度呈正相关(r=0.979,P<0.05),而与5一HT的浓度成负相关(r=-0.958,P<0.05).     

雌激素对大鼠脑缺血再灌注损伤脑皮质EAA含量的影响

目的 研究雌激素对雄性大鼠脑缺血再灌注损伤脑组织兴奋性氨基酸(EAA)含量的影响。方法 采用线栓法制备大鼠大脑中动脉缺血再灌注模型。模型建立后5min内腹腔注射雌激素。相应时间断头取脑。然后测定脑梗死体积、脑组织谷氨酸(GLU)、天门冬氨酸(ASP)及γ氨基丁酸(GABA)含量。结果 脑梗死体积治疗组较缺血对照组明显缩小，缺血对照组脑组织GLU、ASP含量明显高于治疗组。结论 雌激素对脑缺血再灌注损伤有保护作用。其可能的机制为：干扰脑缺血再灌注损伤中EAA代谢而发挥脑保护作用。     

CGRP和NGF对脑局部缺血再灌注大鼠脑组织神经元凋亡及PKCmRNA表达的调节作用

目的研究大鼠脑缺血再灌注后蛋白激酶C信使RNA(PKCmRNA)的表达,探讨降钙素基因相关肽(CGRP)和神经生长因子(NGF)对脑组织缺血再灌注的保护作用及机制。方法采用颈动脉负压分流法制作大鼠脑缺血再灌注模型,采用TUNEL法、原位杂交方法及显微图像分析检测海马及皮质内神经元凋亡和PKCmRNA的表达。结果大鼠缺血再灌注海马及顶叶皮质内神经元凋亡数及PKCmRNA反应产物较正常组增多(P<0.05),而注射CGRP或NGF后神经元凋亡数及PKCmRNA反应产物明显低于缺血再灌注组(P<0.01),二者联合应用效果更加显著(P<0.05)。结论CGRP和NGF抑制缺血神经元凋亡,参与PKCmRNA的调节,二者对缺血神经元有协同修复作用。     

Therapeutic effect of post-ischemic hypothermia duration on cerebral ischemic injury

OBJECTIVE: To study the efficacy of post-ischemic mild brain hypothermia lasting for different time intervals on cerebral ischemic reperfusion injury. METHOD: Male Sprague-Dawley rats were divided into a sham-operated group, normothermia (37-38 degrees C) ischemia group and mild hypothermia (31-32 degrees C) group. The last group was subdivided into four groups: 30 minute hypothermia plus 210 minute normothermia, 60 minute hypothermia plus 180 minute nomothermia,120 minute hypothermia plus 120 minute normothermia, and 240 minute hypothermia (n=8). Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model. Brain tissue was collected following a 20 minute cerebral ischemia and 240 minute reperfusion, and was used to measure the levels of glutamate (Glu), aspartate (Asp), glycine (Gly), gamma-aminobutyric acid (GABA), dopamine (DA), norepinephrine (NE), serotonin(5-HT) and hydroxyindoleacetic acid (5-HIAA), nitrite (NO(2)), endothelin-1 (ET(1)), tumor necrosis factor alpha(TNFalpha) and interleukin-1beta (IL-1beta). Serum was collected to measure the levels of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatine kinase (CK) and its brain band isoenzyme (CK-BB). RESULTS: Hypothermia lasting for 60-240 minutes delayed the decrease in these amino acids, postponed the decrease in DA, NE and 5-HT and increase in hydroxyindoleacetic acid (5-HIAA), and decreased the levels of IL-1beta, TNFalpha, ET(1) and NO(2) in brain tissue. Hypothermia also decreased the levels of LDH, AST, CK and CK-BB in serum as compared to normothermia group (p<0.05 or p<0.01). Hypothermia lasting for 30 minutes delayed the decreases in these amino acids and 5-HT and increase in 5-HIAA in brain tissue (p<0.05), but failed to influence the levels of IL-1beta, TNFalpha, ET(1) and NO(2) in brain tissue and the amounts of LDH, AST, CK and CK-BB in serum as compared to normothermia ischemia group (p>0.05). CONCLUSIONS: Post-ischemic mild brain hypothermia can significantly suppress the excessive release of amino acids, monoamine neurotransmitters and inflammation response in ischemic tissue. It can also stabilize the function of the cell membrane, which is associated with the mechanism of cerebral protection by mild hypothermia. These results suggest that mild hypothermia should be applied immediately after ischemia and last for more than 60 minutes in order to obtain neuroprotective effects.     

前脑缺血及再灌流对大鼠海马神经元凋亡的影响

目的 :探讨脑缺血及再灌流内皮素、降钙素基因相关肽和神经元凋亡变化规律及关系。方法 :前脑缺血及再灌流大鼠为模型 ,检测海马ET、CGRP含量和神经元凋亡。结果 :缺血后 1 5minET显著高于其他各组 ;再灌流后降低 ,1d时最低 ,2d时恢复正常。缺血后 1 5minCGRP显著低于其他各组 ;再灌流后升高 ,1d达高峰后下降。缺血后出现神经元凋亡 ,再灌流后仍增加 ,1d达高峰后下降。ET含量与凋亡细胞呈负相关。CGRP含量与凋亡细胞呈正相关。结论 :缺血和再灌流均可导致神经元凋亡。     

Age influences abnormalities in striatal dopamine metabolism during and after transient forebrain ischemia

Summary Age has been found to be a significant risk factor for brain ischemia and its mortality. After cerebral ischemia, the nigrostriatal dopaminergic system undergoes selective vulnerability with necrosis of striatal neurons. To study the effect of age and transient forebrain ischemia on striatal dopamine metabolism, investigations were performed in 1-year-old (adult) and 2-year-old (aged) male Wistar rats. A 15 min period of bilateral transient incomplete ischemia (ICI) was induced, and the concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), and homovanillic acid (HVA) were measured in the striatum by means of HPLC and electrochemical detection at the end of ischemia without reperfusion, and after 1h, 24h, 72h, 144h, and 288h of postischemic cerebral reperfusion.In normal conditions, no 3-MT was detectable in either age group studied, and no other age-related changes could be found in DA or its metabolites. During ICI, an age-related difference became obvious in the 3-MT concentration, which was higher in aged animals. In this group, DOPAC dropped and DA turnover increased. After 1 h of postischemic reperfusion, the concentrations of DOPAC and HVA, as well as the turnover rate, had increased in both age groups, whereas an increase in the DA concentration became apparent in the adult animals only. The enhancement of the concentration of both DOPAC and HVA was more marked in adult animals than in aged ones. At 24h of postischemic cerebral reperfusion, DA concentration was still elevated in both age groups, and HVA in the 1-year-old animals only. At 72h of postischemic cerebral reperfusion, no differences were obvious between adult experimental animals and controls, whereas the elevated DA concentration persisted in aged animals, being higher than in the control group and in the 1-year-old rats. DA turnover was reduced. Longer periods of postischemic cerebral reperfusion were not found to be followed by any abnormalities compared with controls except for the DA concentration at 288h (1-year-old group); nor were there any differences between the two age groups studied.The data obtained in this investigation clearly indicate age-related differences in the striatal dopaminergic neurotransmission after transient cerebral ischemia, in that in the aged brain reactions are markedly delayed after an injurious event such as ischemia.     

长期饮酒脑缺血大鼠血浆NPY、CGRP、ET含量的测定

目的 探讨长期饮酒对脑缺血大鼠血浆中神经肽Y(NPY)、降钙素基因相关肽(CGRP)、内皮素(ET)含量的影响。方法 选用180～200g雄性Wistar大鼠50只，分为饮水组与饮酒组，饮酒组以7．2％酒精喂养100d，制作长期饮酒模型，后将两组用线拴法制作脑缺血模型，在缺血前、缺血1h、3h、6h分别取血，用放免法测定NPY、CGRP、ET。结果 各时间段饮酒组NPY含量明显高于饮水组P％0．05，缺血3h时，两组血浆NPY含量明显升高，于6h逐渐下降；各时间段饮酒组CGRP均低于饮水组P％0．01，饮水组于缺血3h、饮酒组于缺血1h时，血浆中CGRP明显下降；饮酒组血浆ET于缺血前及缺血1h明显高于饮水组P％0．05，饮水组于缺血3h、饮酒组于缺血1h血浆ET明显升高。结论 脑梗死超早期伴有血浆NPY、CGRP、ET的动态改变，长期饮酒可加重这些变化．增加血浆中缩血管物质的含量减少舒血管物质的含量，进一步减少脑部血液供应。     

Influence of mesenteric lymph reperfusion on neurotransmitter expression in brain tissue of a superior mesenteric artery occlusion shock rat model

BACKGROUND: Previous studies have shown that mesenteric lymph reperfusion (MLR) exacerbates brain injury in a rat model of superior mesenteric artery occlusion (SMAO) shock. However, little is known about the influence of MLR on neurotransmitter expression in brain tissue. OBJECTIVE: To observe the effect of MLR on brain tissue injury by measuring monoamine and cholinergic neurotransmitter levels.DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Institute of Microcirculation, Hebei North University, China; Research Room of Microcirculation and Laboratory of Biochemistry, Department of Pathophysiology, Basic Medical College, Hebei North University between December 2007 and March 2009.MATERIALS: Choline acetyltransferase (ChAT) and acetylcholine esterase (AChE) kits were provided by Nanjing Jiancheng Bioengineering Institute, China; dopamine (DA) and noradrenalin (NE) standards were provided by the National Institute for the Control of Pharmaceutical and Biological Products; HP1100 chromatograph of liquid was provided by Agilent, USA. METHODS: A total of 24 male, Wistar rats were randomly assigned to 4 groups: sham-surgery, MLR, SMAO, and MLR + SMAO groups, with 6 rats in each group. In the MLR or SMAO groups, the mesenteric lymph duct or superior mesenteric artery was blocked for 1 hour. In the MLR + SMAO group, the mesenteric lymph duct and superior mesenteric artery were occluded for 1 hour, followed by 2-hour reperfusion. ChAT and AChE levels were measured using the synthesized and hydrolyzed acetylcholine method, respectively. Liquid chromatography was employed to quantitatively analyze DA and NE levels, using relative retention time and the external standard method. MAIN OUTCOME MEASURES: ChAT, AChE, DA, and NE levels. RESULTS: AChE levels were significantly increased, but ChAT levels were significantly decreased in the MLR and MLR + SMAO groups following 2-hour reperfusion (P < 0.01). However, AChE activity in the MLR + SMAO group was greater than in the MLR group (P < 0.05). DA and NE levels were significantly decreased in the SMAO and MLR + SMAO groups (P < 0.01), while DA levels in the MLR + SMAO group were less than in the SMAO group (P < 0.05). CONCLUSION: MLR exacerbated brain injury in a rat model of SMAO shock, which correlated with the intestinal lymphatic pathway. MLR decreased DA levels, but increased AChE activity, in a rat model of SMAO shock.     

红景天保护缺血再灌注损伤鼠脑细胞的作用及机理研究

目的研究红景天对大鼠脑缺血再灌注损伤的作用。方法４ＶＯ法复制缺血再灌注动物模型;放免法及化学发光法测定乙酰胆碱（Ａｃｈ）、一氧化氮（ＮＯ）及内皮素（ＥＴ）含量;细胞培养观察红景天对神经细胞的作用。结果（１）缺血再灌注组（ＩＲ）Ａｃｈ含量显著低于假手术组（ＳＡＭ）,药物预防后缺血再灌注组（Ｒ＋ＩＲ）及缺血再灌注后药物治疗组（ＩＲ＋Ｒ）较ＩＲ组显著升高。（２）ＩＲ组ＮＯ含量显著高于ＳＡＭ组,Ｒ＋ＩＲ组及ＩＲ＋Ｒ组ＮＯ含量显著降低。（３）ＩＲ组ＥＴ含量显著高于ＳＡＭ组而Ｒ＋ＩＲ组显著降低。（４）红景天甙培养组细胞存活率及ＬＤＨ含量明显高于对照组,ＮＭＤＡ损伤＋红景天甙组细胞存活率明显高于ＮＭＤＡ损伤组,ＬＤＨ含量却明显降低。结论红景天对大鼠脑缺血再灌注损伤时脑神经细胞具有保护作用。     

CGRP和NGF对大鼠全脑缺血再灌注脑组织Bcl-2蛋白表达的影响

目的 :观察降钙素基因相关肽 (CGRP)和神经生长因子 (NGF)对缺血神经元 Bcl- 2蛋白表达的影响 ,探讨其神经保护功能的分子机制方法 :应用颈动脉负压分流法是作大鼠短暂性全脑缺血模型 ;于再灌注开始 ,颈颈动脉注入 CGRP、CGRP和 NGF;应用免组织化学方法检测经元 Bcl- 2蛋白的表达。结果 :CGRP组大脑皮层及海马区 Bcl- 2免疫反应阳性百分率为分别 70 .83± 8.95和 4.17± 0 .34 ,较全脑缺血再灌注组 (2 4.88± 2 .88和 2 .95± 0 .34 )明显增加 (P<0 .0 1) ;CGRP加 NGF组大脑皮质及海马区 Bcl- 2免疫反应阳性细胞百分率分别为 83.2 3± 5 .97和 8.0 3±1.5 6 ,明显高于 CGRP组和全脑缺血再灌注组 (P<0 .0 1)。结论 :CGRP可上调缺血再灌注脑组织 Bcl- 2蛋白的表达 ,CGRP的神经保护作用可能与其上调 Bcl- 2蛋白表达有关 ;CGRP和 NGF的联合应用加强了上调 Bcl- 2蛋白表达的作用