注射用丹参多酚酸对大鼠脑缺血再灌注线粒体ATP酶活性的影响

目的探讨注射用丹参多酚酸对大鼠脑缺血再灌注线粒体ATP酶活性的影响。方法将54只雄性SD大鼠随机分成3组(n=18):假手术组(Sham组)、缺血再灌注组(IR组)、丹参多酚酸组(Salvianolate组)。HE染色法观察大脑神经元的组织病理学变化;TTC染色检测脑梗死体积;分光光度计发法线粒体丙二醛含量和线粒体Na~+/K~+ATP酶、Ca~(2+)ATP酶、Mg~(2+)ATP酶活性。结果假手术组大鼠脑组织红染,未见梗死灶;丹参多酚酸组神经细胞变性坏死程度、脑梗死面积较缺血再灌注组明显减轻;与缺血再灌注组相比,丹参多酚酸组线粒体丙二醛含量下降(P0.05)和线粒体Na~+/K~+ATP酶、Ca~(2+)ATP酶、Mg~(2+)ATP酶活性升高(P0.05)。结论注射用丹参多酚酸对缺血再灌注损伤有保护作用,其机制与提高线粒体ATP酶活性有关。     

SIRT2对脑缺血再灌注损伤后神经保护作用及机制研究

目的 探讨SIRT2对脑缺血再灌注损伤的神经保护作用及其相关机制.方法 将CD-1小鼠随机分为假手术组和模型组.模型组分别在再灌注后6、12和24h 3个时间点处死取脑,Real-time PCR检测皮质SIRT2mRNA表达变化,Western blot半定量检测再灌注后12、24h皮质中SIRT2蛋白水平的表达变化,用免疫荧光来检测SIRT2在缺血前后皮质中的定位;随后将小鼠随机分为Dmso组和AGK-2(SIRT2特异性抑制剂)组,两组都用线拴法建立t-MCAO模型,24h后用CHOPP评分标准来评价缺血后小鼠的神经功能损伤,TTC染色观察梗死体积,并分别用MPO、SOD试剂盒来检测各组中的炎症和氧化应激的水平.结果 和假手术组相比,再灌注6、12、24h后皮质中SIRT2 mRNA水平升高(P＜0.05),再灌注后12、24h SIRT2蛋白水平升高(P＜0.05);侧脑室给予AGK-2 5μl后,AGK-2(5 mmol/L)和DMSO对照组比较梗死体积增大(P＜0.05),神经功能损害更为严重(P＜0.05),缺血侧中MPO水平增加(P＜0.05),SOD水平下降(P＜0.05);AGK-2( 2.5 mmol/L)和对照组比较以上各指标均没有显著性差异.结论 SIRT2可以通过降低脑组织中的炎症和氧化应激水平对脑缺血再灌注损伤起到神经保护作用.     

丹参素防治脑缺血-再灌注损伤的机制及研究进展

<正>缺血性脑卒中的发病率逐年上升,具有高致残率、高死亡率,严重危害人类健康~([1～3])。积极静脉溶栓是其临床主要治疗方式,组织型纤溶酶原激活物(tissue-type plasminogen activator,t-PA)是目前较为公认的溶栓剂,但时间窗短、颅内出血风险及过敏反应等副作用限制了临床应用~([4,5]),且易继     

HMGB1抑制剂预处理对大鼠心肺复苏后脑缺血再灌注损伤及TLR4/NF-κB信号通路的影响

目的 探讨高迁移率族蛋白B1(HMGB1)抑制剂预处理对大鼠心肺复苏后脑缺血再灌注损伤及Toll样受体4(TLR4)/核转录因子-κB(NF-κB)信号通路的影响.方法 建立大鼠心肺复苏模型(封闭气管3～4 min),随机分为模型组,甘草酸(HMGB1抑制剂)低、中、高剂量组(分别以1、2、3 mg/mL甘草酸溶液按体...     

脑缺血再灌注损伤机制研究进展

脑缺血一定时间恢复血液供应后，其功能不但未能恢复，却出现了更加严重的脑机能障碍，称之为脑缺血再灌注损伤（cerebral ischemia reperfusion injury，CIR）。缺血再灌注损伤涉及极其复杂的病理生理过程，其中各个环节、各种影响因素间的相互作用尚未完全阐明。现对脑缺血再灌注损伤一些重要机制进行简述如下。     

VEGF治疗脑缺血再灌注损伤的分子机制研究

目的 通过检测血管内皮生长因子（VEGF）治疗兔脑缺血再灌注损伤的有关分子表达情况,探讨其分子机制.方法 采用兔大脑中动脉阻塞（MCAO）2h再灌注72h模型,在再灌注即刻,应用微量进样器将VEGF立体定向导入梗死灶周,于再灌注72h断头取脑,应用免疫组化方法检测缺血半暗带区caspase-3和细胞外信号调节激酶1（estracellular signal-regulated kinase,ERK1）的表达情况.结果 VEGF治疗后缺血半暗带区caspase-3和ERK1表达明显减低.结论 VEGF可能通过抑制caspase-3和ERK1表达发挥治疗作用.     

胃酶抑素A通过上调p-ERK1/2的表达来保护大鼠脑缺血再灌注损伤

目的 探讨胃酶抑素A(Pepstatin A)保护大鼠脑缺血再灌注损伤的潜在机制。方法 将48只成年雄性健康Sprague-Dawley大鼠随机分配至假手术组(16只)、生理盐水对照组(16只)及Pepstatin A干预组(16只); 大鼠大脑中动脉缺血再灌注模型遵照Zea longa线栓法制备,即缺血2 h即恢复血流灌注,再灌注24 h后处死大鼠; 干预组及对照组在脑缺血再灌注即刻分别经腹腔注射Pepstatin A配置液(0.2 mL/10 g)或等体积生理盐水; 脑缺血2 h再灌注24 h时采用标准评分法行神经功能缺损评分; 假手术组、对照组及干预组中随机各取8只检测脑梗死体积,余下8只大鼠行western blot检测p-ERK1/2及Caspase-3的表达水平。结果 神经功能缺损评分显示,假手术组大鼠行为学表现正常,评分为0分,干预组大鼠的评分均显著低于对照组(P<0.05)。TTC染色显示,假手术组脑组织无梗死灶,干预组大鼠的相对脑梗死体积显著低于对照组(P<0.05)。Western blot检测显示,对照组p-ERK1/2蛋白的表达水平显著高于假手术组(P<0.05); 干预组该蛋白的表达水平较对照组显著增加(P<0.05); 干预组Caspase-3蛋白的相对表达水平显著低于对照组(P<0.05)。结论 Pepstatin A可能通过上调p-ERK1/2的表达来减少脑梗死体积及细胞凋亡发生,从而保护大鼠脑缺血再灌注。     

大鼠全脑缺血/再灌注模型之比较研究

目的：观察常用大鼠全脑缺血／再灌注模型在缺血及再灌注过程中ｒＣＢＦ及ＥＥＧ的变化。方法：用ｐｅｒｆｌｕｘ－３型多谱勒灌注监测测定局部脑血流量变化。用脑电图仪监测脑电波变化。结果：２ＶＯ组,３ＶＯ组与颈动脉分流组在缺血２５ｍｉｎ时ｒＣＢＦ较Ｖ４ＶＯ组下降明显。３ＶＯ组颈动脉分流组再灌注３０ｓ内ｒＣＢＦ上升较４ＶＯ组及２ＶＯ组变化较慢。     

胰岛素样生长因子-1对大鼠脑缺血再灌注损伤的作用机制研究

目的观察尾静脉注射胰岛素样生长因子-1(IGF-1)时大鼠脑缺血再灌注损伤的影响，探讨IGF-1的作用机制。方法TTC染色测脑梗死体积，光镜检查细胞损伤变化．免疫组化法测Caspase-3阳性表达。结果与缺血再灌注组相比，IGF-1灶性脑缺血再灌注损伤有保护作用，在脑缺血损伤时IGF-1能通过血脑屏障，IGF-1可通过抑制神经细胞调亡发挥作用。     

高血压大鼠脑缺血再灌注损伤时的病理学变化

目的 研究高血压大鼠在脑缺血损伤时的病理改变.方法 用线拴法将肾性高血压大鼠制作成脑缺血再灌注模型,在光镜和透射电镜下观察脑组织的病理和超微结构改变.结果 高血压组大鼠与正常大鼠相比,在局灶性缺血再灌注损伤时有明显的组织学改变.结论 高血压可经过多种机制加剧脑缺血性损伤.     

Induction and subcellular localization of high-mobility group box-1 (HMGB1) in the postischemic rat brain

High-mobility group box-1 (HMGB1) was originally identified as a ubiquitously expressed, abundant nonhistone DNA-binding protein. Recently, it was found to act as a cytokine-like mediator of delayed endotoxin lethality and of acute lung injury. Previously, we reported that HMGB1 is massively released extracellularly and plays a cytokine-like function in the postischemic brain. In the present study, we examined the expression profile and cellular distribution of HMGB1 in rat brain after transient focal cerebral ischemia. The expression of HMGB1 in infarction areas in the ipsilateral sides gradually declined over 2 days after 1 hr of middle cerebral artery occlusion (MCAO) to below the basal level. However, after 3 days of reperfusion, HMGB1 level increased to above the basal level, especially in infarction cores, and this delayed induction was then maintained for several days. Immunohistochemistry using a polyclonal antibody against HMGB1 revealed its detailed expression pattern and subcellular localization in the postischemic brain. HMGB1 was found to be widely expressed throughout the normal brain and to be localized to the nuclei of almost all neurons and oligodendrocyte-like cells. After 1 hr of MCAO, HMGB1 immediately translocated from the neuron nuclei to the cytoplasm and subsequently was depleted from neurons during the excitotoxicity-induced acute damaging process. Moreover, beginning 2 days after reperfusion, HMGB1 was notably induced in activated microglia, astrocytes, and in microvascular structures, and these delayed gradual inductions were sustained for several days. These findings suggest that HMGB1 functions as a cytokine-like mediator in a paracrine and autocrine manner in the postischemic brain.     

Caffeine facilitation of glutamate release from rat cerebral cortex nerve terminals (synaptosomes) through activation protein kinase C pathway: an interaction with presynaptic adenosine A1 receptors

The present study used nerve terminals (synaptosomes) isolated from rat cerebral cortex to investigate the relationship between caffeine and 4-aminopyridine (4AP)-evoked endogenous excitatory neurotransmitter glutamate release. Micromolar concentrations of caffeine facilitated 4AP, but not KCl or ionomycin-evoked glutamate release from synaptosomes. This release facilitation resulted from an enhancement of vesicular and nonvesicular release and associated with an increase both in 4AP-evoked depolarization of the synaptosomal plasma membrane potential and in 4AP-evoked increase in the cytoplasmic free Ca(2+) concentration ([Ca(2+)](C)). In addition, the release facilitation by caffeine was significantly reduced in synaptosomes pretreated with a wide spectrum blocker of N- and P/Q-type Ca(2+) channels, omega-conotoxin MVIIC. Furthermore, protein kinase C (PKC) activator and inhibitor, respectively, superseding or suppressing the caffeine-mediated facilitation of glutamate release. These results concluded that caffeine exerts their presynaptic facilitatory effect, likely through the activation of PKC pathway, which subsequently enhances terminal excitability and Ca(2+) entry to cause an increase in evoked glutamate release from rat cerebrocortical nerve terminals. Additionally, this release facilitation may involve an interaction of caffeine with presynaptic adenosine A1 receptors as adenosine A1 receptor inhibition abolished the caffeine-mediated facilitation of evoked glutamate release.