共查询到20条相似文献,搜索用时 10 毫秒
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目的:研究缺血后适应对大鼠局灶性脑缺血再灌注后谷氨酸(Glu)浓度变化的影响。方法:建立大鼠大脑中动脉阻塞(middle cerebral artery occlusion,MCAO)模型,将36只雄性SD大鼠随机分为假手术(Sham)组、脑缺血再灌注(I/R)组和缺血后适应(I Postcond)组,每组12只。应用高效液相色谱检测缺血脑组织匀浆Glu浓度。结果:局灶脑缺血再灌注6 h后,I Postcond组Glu浓度相较I/R组明显降低(P<0.01),局灶脑缺血再灌注24 h后,I Postcond组Glu浓度较I/R组低,但两者差异亦无显著性(P>0.05)。结论:本研究表明,I Postcond能够减轻MCAO大鼠模型中I/R损伤。细胞间隙Glu清除的加速可能是其重要保护机制之一。 相似文献
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目的: 研究L-丝氨酸对大鼠永久性脑梗死的神经保护作用、治疗剂量及有效治疗时间窗,并探讨相关作用机制。方法: 制作大鼠永久性大脑中动脉栓塞(pMCAO)模型,腹腔注射L-丝氨酸,通过神经行为学评分、脑梗死体积测定和尼氏染色法,观察L-丝氨酸的治疗剂量效应(56 mg/kg、168 mg/kg和504 mg/kg治疗组)和治疗时间窗(1 h、3 h、6 h、12 h和24 h治疗组);并测定丝氨酸消旋酶抑制剂对L-丝氨酸疗效的影响。利用激光多普勒血流监测仪观察缺血区血供及L-丝氨酸对缺血区局部脑血流量的影响。结果: 与pMCAO组相比,L-丝氨酸于pMCAO后3 h使用,168 mg/kg和504 mg/kg两个剂量都能较好地降低神经行为学评分,减少脑梗死体积,抑制海马CA1区神经细胞的丢失。在治疗时间窗的研究中,L-丝氨酸在pMCAO后6 h内治疗具有明显的神经保护作用,12 h及以后使用,神经保护作用不明显。丝氨酸消旋酶抑制剂不改变L-丝氨酸的疗效。脑缺血30 min时注射L-丝氨酸可明显增加缺血区局部脑血流量,并且这一作用不受甘氨酸受体阻断剂士的宁的影响。结论: L-丝氨酸对永久性脑梗死具有神经保护作用,其机制可能部分与增加缺血区皮质的血供有关。 相似文献
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We and others have identified that inhibition of cyclooxygenase might not be the optimal approach to limiting brain damage after stroke. Now we are investigating the unique properties of the various prostaglandin receptors to determine whether blocking those that mediate toxicity or stimulating those that reduce toxicity will improve neurological outcomes. Here, we determined the respective contribution of the prostaglandin I2 (PGI2) receptor in transient middle cerebral artery (MCA) occlusion (tMCAO) and permanent MCAO (pMCAO) preclinical stroke models by using male wildtype (WT) and IP receptor knockout (IP−/−) C57Bl/6 mice. In addition, we investigated the putative preventive and therapeutic effects of the IP receptor agonist beraprost. The infarct volumes and neurological deficit scores (NDS) were significantly greater in IP−/− than in WT mice after both tMCAO and pMCAO. Interestingly, beraprost pretreatment (50 or 100 μg/kg p.o.) 30 min before tMCAO and post-treatment (100 μg/kg p.o.) at 2 or 4.5 h of reperfusion significantly reduced the neurological deficit score and infarct volume in WT mice. Post-treatment with beraprost (100 μg/kg p.o.) 4.5 h after pMCAO also significantly decreased neurological deficits and infarct volume in WT mice. Together, these novel findings suggest for the first time that PGI2 IP receptor activation can attenuate anatomical and functional damage following ischemic stroke. 相似文献
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张朝弘 《国际病理科学与临床杂志》2013,33(3):246-250
氧化应激是发生脑缺血/再灌注(ischemia/reperfusion,I/R)损伤的重要机制.近来研究发现,还原型烟酰胺腺嘌呤二核苷酸磷酸(nicotinamide adenine dinucleotide phosphate,NADPH)氧化酶产生的活性氧对脑I/R后的氧化应激起到重要的作用.一些方法(如常压高氧、缺血后处理)和一些药物(如罗布麻宁、替米沙坦、桦木酸、加兰他敏、雷公藤红素等)可以NADPH氧化酶为靶点治疗脑I/R损伤. 相似文献
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目的:改良传统的开颅造模法,建立一种稳定、可靠的大鼠脑缺血再灌注模型。方法:20只SD大鼠随机分为假手术与缺血再灌注组,每组10只,分别行假手术操作及改良模型制作。改良模型为,大鼠开颅后暴露左侧大脑中动脉(middle cerebral artery,MCA),将直径0.12 mm的不锈钢丝放置于MCA下,近其主干,钢丝两端架于颞骨表面120 min,撤去钢丝即再灌注。假手术仅暴露MCA,不进行缺血及再灌注。大鼠再灌注24 h,通过神经功能缺失评分,TTC染色,神经元计数及病理形态学的方法对模型进行评价。结果:改良后的造模成功率为100%,梗死灶位于额、顶叶皮层,病理形态学表现为典型的缺血性改变,正常神经元数减少(P0.01)。神经功能缺失评分1.3±0.5,脑梗死体积比率为5.32%±1.28%,与假手术组相比均有统计学意义(P0.01)。结论:这一改良模型阻断及恢复MCA血流明确,梗死灶的大小、位置稳定,死亡率低,为脑缺血再灌注机制的研究及治疗方法的探讨提供了有益帮助。 相似文献
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目的:探讨橄榄苦苷(OE)对大鼠局灶性脑缺血/再灌注损伤和炎性反应的作用。方法:雄性SD大鼠随机分为假手术组(Sham组)、溶媒处理组(Vehicle组)和OE处理组(OE组)。用线栓法制作大脑中动脉脑缺血/再灌注(MCAO/R)模型。TTC染色检测脑梗死体积,免疫组化法检测缺血侧大脑皮层髓过氧化物酶(myeloperoxidase,MPO)和肿瘤坏死因子(TNF-α)表达,Western Blot法检测基质金属蛋白酶-9(matrix metallopeptidase 9,MMP9)及基质金属蛋白酶-2(matrix metallopeptidase 2,MMP2)的表达。结果:(1)Vehicle组大脑缺血侧有明显的梗死灶,而OE处理组脑梗死体积明显有所缩小(P0.01)。(2)Vehicle组MPO和TNF-α表达与Sham组相比显著提高(P0.01),而OE组两者的表达较Vehicle组明显降低(P0.01,P0.05)。(3)Western Blot显示:Vehicle组MMP2、MMP9的表达水平较Sham组显著提高,而OE处理下调两者表达(P0.01,P0.05)。结论:OE可能通过抑制炎性反应保护脑缺血再灌注损伤。 相似文献
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Ischemia/reperfusion (I/R) injury accounts to be a prime cause of neurological deficit following stroke. This study aimed to explore the neuro-protective effects of Xanthoangelol (XAG) on I/R-induced injury in both in vivo and in vitro models. Our data demonstrated that XAG can shrink infarct size and brain edema in middle cerebral artery occlusion (MCAO) model. In addition, XAG was capable of alleviating the neurological deficit in rats that have undergone MCAO procedure. Meanwhile, antiapoptotic activities of XAG against I/R-induced neuronal injury were evidenced and further illustrated that XAG elicits antiapoptotic activities by suppressing excessive oxidative stress via nuclear factor erythroid-2-related factor 2 activation. Overall, our study revealed that XAG displayed the potential to be utilized as a neuroprotective agent against I/R-induced neurological injury. 相似文献
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目的观察银杏叶提取物(extract of Ginkgo biloba,EGB)对大鼠局灶性脑缺血再灌注梗死区胶质纤维酸性蛋白(GFAP)表达的影响。方法采用改良线栓法建立大鼠大脑中动脉阻塞脑缺血再灌注模型。观察再灌注1~4d里大鼠神经功能缺损程度并应用免疫组织化学法、Metamoph图像分析系统对结果进行分析。结果EGB药物组神经功能评分较缺血再灌组好(P<0.05),GFAP阳性细胞于脑缺血2h再灌注24h后即已出现,48、72、96h阳性细胞表达量增加,其中以72h为最多,EGB可抑制缺血后GFAP的表达(P<0.05)。结论局灶性脑缺血后可诱导脑组织GFAP表达增强,EGB可抑制脑缺血再灌注后星形胶质细胞GFAP的高表达,提示EGB对缺血诱导的星形胶质细胞活化具有抑制作用,可能对脑缺血损伤的恢复起重要作用。 相似文献
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目的探讨白藜芦醇对大鼠脑缺血再灌注损伤后突触素表达的影响。方法 72只SD雄性大鼠随机分成假手术组(Sham)、缺血对照组(Con)和白藜芦醇组(Res),每组24只。脑缺血3h后腹腔注射白藜芦醇或无水乙醇,连用7d。脑缺血24h时,TTC法测量脑梗死体积,干湿称重法检测脑含水量。缺血24h、7d、14d分别行Bederson神经功能缺损评分,免疫组织化学法及Western blotting检测突触素蛋白的表达。结果 TTC染色显示,缺血对照组和白藜芦醇组脑梗死体积较假手术组高(P0.05),而白藜芦醇组较缺血对照组显著减小(P0.05)。脑含水量检测显示,缺血对照组和白藜芦醇组较假手术组明显增高(P0.05),但白藜芦醇组较缺血对照组显著降低(P0.05)。神经功能缺损评分显示,24h、7d、14d缺血对照组和白藜芦醇组显著高于假手术组(P0.05),但白藜芦醇组较缺血对照组显著降低(P0.05)。免疫组织化学显示,缺血对照组24h时脑缺血皮质突触素阳性表达减少,7d、14d时逐渐增加,但均较假手术组显著减少;白藜芦醇组各时间点均较缺血对照组明显增加,14d增加更明显。Western blotting显示,缺血对照组24h、7d、14d脑缺血区皮质突触素蛋白表达较假手术组显著降低(P0.05),但7d、14d时逐渐增加;白藜芦醇组各时间点较缺血对照组显著增强(P0.05),14d时增加更显著。结论白藜芦醇治疗可增强脑缺血大鼠突触素的表达,改善神经功能。 相似文献
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水通道蛋白-4在大鼠急性脑缺血再灌注脑组织中的表达 总被引:1,自引:1,他引:0
目的:探讨水通道蛋白-4(AQP4)在急性脑缺血再灌注脑组织中的表达规律。方法:线栓法建立右侧大脑中动脉栓塞(MCAO)模型,分为假手术组、栓塞组和再灌注组。对脑组织病理观察、TTC染色,免疫组织化学、原位杂交组织化学、荧光定量PCR和免疫印迹检测。结果:栓塞组在右侧基底节区见细胞器肿胀、细胞体积增大,但细胞膜和血脑屏障结构完整,TTC染色缺血面积明显增加。所有再灌注组右侧基底节区的细胞肿胀减轻,再灌注早期组可见轻度血管源性水肿,TTC染色缺血面积逐渐缩小。AQP4基因和蛋白的表达量明显下降,分别与栓塞组比较均存在显著性差异。再灌注后各组AQP4基因和蛋白表达明显下降,但均高于假手术组。结论:无论是脑缺血或是再灌注,AQP4的表达均与细胞内水肿的程度一致,再灌注早期可出现血管源性水肿,再灌注越早脑细胞越容易恢复正常。 相似文献
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红景天苷对局灶性脑缺血再灌注大鼠突触超微结构的影响 总被引:6,自引:0,他引:6
目的研究红景天苷对局灶性脑缺血/再灌注损伤后突触结构和数密度的变化。方法采用线栓法制造大鼠大脑局灶缺血(2h)/再灌注模型(I/R模型),于灌注后1d、3d、7d、14d时间点断头取脑,电镜观察突触结构和数密度的变化。结果I/R模型组数目减少,7d降至最低,14d突触数目回升;突触结构随再灌注时间延长损伤加重,14d有所恢复;红景天组突触损害程度减轻,突触数目增加(P<0.05),突触数密度恢复的时间提早至7d。结论红景天苷可以减轻脑缺血再灌注后突触的损伤,易化突触可塑性。 相似文献
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目的:探讨八肽胆囊收缩素(CCK-8)对局部脑缺血/再灌注损伤的影响及其可能机制。方法:采用线栓法大鼠局部脑缺血再灌注模型,观察侧脑室(icv)注射CCK-8或其受体拮抗剂-丙谷胺对脑缺血1h再灌注24h大鼠脑梗死体积、局部脑血流量(rCBF)、不同脑区一氧化氮(NO)、丙二醛(MDA)含量的影响。结果:(1)脑缺血前给予不同剂量的CCK-8均可缩小脑梗死体积,但只有CCK-8剂量为1.0μg、2.0μg时这种差别才有显著性(均P<0.05)。预先给予丙谷胺可完全拮抗CCK-8的作用;单纯给予丙谷胺可加重脑缺血损伤。(2)CCK-8可显著抑制脑缺血/再灌注损伤引起的梗死区、半暗区NO水平的升高;抑制梗死区MDA含量的增加(P<0.05);再灌注24h时,CCK-8组rCBF显著高于正常值(P<0.05)。结论:中枢内、外源性CCK-8均具有减轻局部脑缺血/再灌注损伤的作用,其机制可能和抑制脑缺血或再灌注时的自由基损伤及增加rCBF有关。 相似文献
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Wei Guo Guoying Feng Yanying Miao Guixiang Liu 《Immunopharmacology and immunotoxicology》2014,36(3):211-223
Brain edema is a major consequence of cerebral ischemia reperfusion. However, few effective therapeutic options are available for retarding the brain edema progression after cerebral ischemia. Recently, rapamycin has been shown to produce neuroprotective effects in rats after cerebral ischemia reperfusion. Whether rapamycin could alleviate this brain edema injury is still unclear. In this study, the rat stroke model was induced by a 1-h left transient middle cerebral artery occlusion using an intraluminal filament, followed by 48?h of reperfusion. The effects of rapamycin (250?μg/kg body weight, intraperitoneal; i.p.) on brain edema progression were evaluated. The results showed that rapamycin treatment significantly reduced the infarct volume, the water content of the brain tissue and the Evans blue extravasation through the blood–brain barrier (BBB). Rapamycin treatment could improve histological appearance of the brain tissue, increased the capillary lumen space and maintain the integrity of BBB. Rapamycin also inhibited matrix metalloproteinase 9 (MMP9) and aquaporin 4 (AQP4) expression. These data imply that rapamycin could improve brain edema progression after reperfusion injury through maintaining BBB integrity and inhibiting MMP9 and AQP4 expression. The data of this study provide a new possible approach for improving brain edema after cerebral ischemia reperfusion by administration of rapamycin. 相似文献
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Modulation of the balance between cannabinoid CB(1) and CB(2) receptor activation during cerebral ischemic/reperfusion injury 总被引:3,自引:0,他引:3
Cannabinoid receptor activation has been shown to modulate both neurotransmission (CB(1)) and neuroinflammatory (CB(2)) responses. There are conflicting reports in the literature describing the influence of cannabinoid receptor activation on ischemic/reperfusion injury. The goal of this study was to evaluate how changing the balance between CB(1) and CB(2) activation following cerebral ischemia influences outcome. CB(1) and CB(2) expression were tested at different times after transient middle cerebral artery occlusion (MCAO) in mice by real-time RT-PCR. Animals subjected to 1 h MCAO were randomly assigned to receive different treatments: a CB(1) antagonist, a CB(2) antagonist, a CB(2) agonist, a CB(1) antagonist plus CB(2) agonist, a CB(2) antagonist plus CB(2) agonist or an equal volume of vehicle as control. Cerebral blood flow was continuously monitored during ischemia; cerebral infarction and neurological deficit were tested 24 h after MCAO. Cerebral CB(1) and CB(2) mRNA expression undertook dynamic changes during cerebral ischemia. The selective CB(1) antagonist significantly decreased cerebral infarction by 47%; the selective CB(2) antagonist increased infarction by 26% after 1 h MCAO followed by 23 h reperfusion in mice. The most striking changes were obtained by combining a CB(1) antagonist with a CB(2) agonist. This combination elevated the cerebral blood flow during ischemia and reduced infarction by 75%. In conclusion, during cerebral ischemia/reperfusion injury, inhibition of CB(1) receptor activation is protective while inhibition of CB(2) receptor activation is detrimental. The greatest degree of neuroprotection was obtained by combining an inhibitor of CB(1) activation with an exogenous CB(2) agonist. 相似文献
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M. Kanter 《Experimental and molecular pathology》2010,89(3):314-320
Testicular torsion causes an enhanced formation of reactive oxygen species, which contributes to the pathophysiology of tissue damage. The aim of this study was to investigate the protective effect of melatonin on testicular torsion/detorsion-induced ischemia–reperfusion (I/R) injury. A total of 24 male Wistar albino rats were divided into three groups of 8 animals each: control, I/R, and I/R treated with melatonin. The ischemia period was 5 h and orchiectomy was performed after 5 h of detorsion. Melatonin (10 mg/kg, intraperitoneally [i.p.]) was administrated only once, 40 min prior to detorsion. Spermatogenesis and mean seminiferous tubule diameter (MSTD) were significantly decreased in the I/R groups were compared to the control group. Furthermore, the melatonin treated animals showed an improved histological appearance in the I/R group. Our data indicate a significant reduction in the activity of TUNEL; there was a rise in the expression of proliferating cell nuclear antigen (PCNA) and testosterone in testes tissue of the I/R group treated with melatonin therapy. Electron microscopy of the testes of the rats demonstrated that pretreatment with melatonin was particularly effective in preventing mitochondrial degeneration, dilatation of SER, and enlarged intercellular spaces in both Sertoli and spermatid cells in the I/R treated animals. We believe that further preclinical research into the utility of melatonin may indicate its usefulness as a potential treatment on testes injury after I/R in rats. 相似文献
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目的观察脑缺血再灌注(I/R)损伤大鼠脑组织中补体C1q与C3c的表达,探讨补体反应与小胶质细胞在脑I/R损伤中的作用及其机制。方法 48只SD雄性大鼠随机分为正常对照组、假手术组、I/R模型24 h、72 h、7 d、15 d组,线栓法建立局灶性大脑中动脉闭塞再灌注模型。尼氏体染色观察神经元结构,免疫组化法检测CD11b以及C1q、C3c的表达水平。结果与sham组相比,I/R 24 h组脑组织尼氏体染色加深,随后染色反应减弱,尤以I/R 72 h组减少最为显著;I/R 24 h组脑组织CD11b表达增多且在I/R 72 h组达到峰值,随后逐渐减少,与sham组比较,全部模型组差异显著(P0.05);I/R 24 h组脑组织C1q与C3c急剧增多且在I/R 7 d组达到峰值,随后见下降趋势,全部模型组与sham组比较差异显著(P0.05)。结论脑I/R损伤大鼠脑组织中C1q、C3c与CD11b的表达呈正相关。提示脑I/R损伤后,启动了脑内固有免疫反应,补体C1q与C3c活化,同时激活小胶质细胞,在脑I/R损伤中起到保护或损伤作用。 相似文献
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目的: 探讨影响线栓法复制小鼠局灶性脑缺血再灌注模型稳定性的因素。方法: 60只雄性昆明小鼠按体重分为3组:A组(18-21 g)、 B 组(22-28 g)和C组(30-35 g)。线栓栓塞法制备大脑中动脉缺血再灌注模型。模型评价指标包括:PRM2激光多普勒脑血流仪检测大脑中动脉供血区的血流,按Longa标准进行小鼠运动行为评分,TTC 染色法测量小鼠脑梗死灶体积,ELISA法检测脑皮层丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性。结果: 与 C组相比, A、B两组模型成功率高(P<0.05),尤以B组模型成功率更高;A组死亡率显著高于B组和C组(P<0.05);A、B两组行为学评分显著高于C组(P<0.05),表现出明显的神经功能障碍;A、B两组小鼠脑梗死灶的体积显著高于C组 (P<0.05),表现出明显的脑损伤,损伤侧脑皮层中MDA含量明显升高,SOD活性明显下降。结论: 小鼠体重与线栓直径良好匹配、进线深度和24 ℃左右的室温是保证造模成功的3个重要因素。脑组织脂质过氧化反应可作为脑缺血再灌注损伤的有效指标。 相似文献
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目的:观察美满霉素联合栀子苷对大鼠缺血性脑损伤神经元凋亡的拮抗作用和对脑组织的保护作用。方法:SD大鼠随机分为假手术组、脑缺血再灌注组、美满霉素组、栀子苷组和美满霉素联合栀子苷组。用线栓法建立大鼠右侧局灶性脑缺血再灌注模型,在体分别观察美满霉素和栀子苷单一和两者联合干预缺血性脑损伤。TTC染色观察脑梗死面积,H-E染色观察海马神经元形态学的变化,TUNEL染色观察凋亡情况。结果:美满霉素和栀子苷均能有效促进脑损伤后海马组织的恢复并能拮抗神经元的凋亡,与脑缺血再灌注组相比差异具有统计学意义;两者联合应用较单一使用具有较好的效果。结论:美满霉素联合栀子苷对缺血性脑组织具有保护作用并能有效拮抗神经元的凋亡。 相似文献