Leonurine protects ischemia-induced brain injury via modulating SOD,MDA and GABA levels

The present study was designed to investigate the protective effects of leonurine, a compound purified from Herba Leonuri that is active on ischemic rat behavior and cortical neurons, and explore the underlying mechanism. The general rat activity, cortical neuron morphology, superoxide dismutase (SOD), malondialdehyde (MDA), g-aminobutyric acid (GABA) and glutamate decarboxylase 67 (GAD67) levels were measured. We found leonurine significantly improve the general activity of rats in an open-field test, which was associated with attenuated neuronal damage induced by ischemia. Moreover, serum SOD activity was significantly greater, MDA level lower in the leonurine group as compared with ischemia group. In addition, GABA content in the cerebral cortex was significantly greater in high-dose leonurine group. Correspondingly, GAD67 protein level coincided with the GABA level. Taken together, our results demonstrated that leonurine attenuated brain injury during ischemia via antioxidative and anti-excitotoxicity effects by targeting GABA and leonurine might become a useful adjuvant neuroprotective agent.     

玉米幼芽提取物对垂体后叶素致家兔心肌缺血的保护作用

采用耳缘静脉注射垂体后叶素(pituitrin, Pit)诱发家兔急性心肌缺血,观察Ⅱ导联心电图心率、S-T段位移及T波波幅;心肌酶(谷草转氨酶、乳酸脱氢酶、肌酸激酶);心肌组织中谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)活性和脂质过氧化物丙二醛(MDA)含量的变化.结果显示,玉米幼芽提取物可减轻垂体后叶素诱发的家兔心电图缺血性改变(心率变缓、S-T段抬高、T波高耸),抑制血清中AST、LDH、CK活性的升高,并可增加缺血心肌组织中GSH-Px和SOD活性,抑制MDA含量升高.结果表明,玉米幼芽提取物对垂体后叶素致家兔心肌缺血有一定的保护作用.     

缺血预处理对兔脊髓缺血再灌注损伤的保护作用

目的：观察缺血处理对脊髓缺血再灌注损伤的影响。方法：夹闭左肾动脉起点以下腹主脉３５ｍｉｎ，制作脊髓缺血损伤模型。在制作上述模型前预处理组动物夹闭腹主动脉５ｍｉｎ，松夹１０ｍｉｎ，松夹１０ｍｉｎ，反复３次进行缺血预处理，术后进行神经功能评分和观察组织病理学变化。结果：与对照组相比，预处理组神经功能恢复评玢明显增加（术后２４ｈ，ｐ０．０１；４８ｈ，ｐ〈０．０５），组织病理学变化明显减轻或消失。结论：缺     

Regional variation of extracellular space in the hippocampus

The factors responsible for the unusual susceptibility of the hippocampus to seizures and ischemic cell damage are not well understood. The CA1 pyramidal subfield of the hippocampus is particularly vulnerable to seizure activity and damage after ischemia. The possibility was examined that regional differences exist in extracellular volume, which might influence neuronal excitability and response to injury in the hippocampus. CA1 stratum pyramidale exhibited an exceptionally low extracellular volume fraction (EVF) of 0.12, whereas the EVFs of CA3 and dentate were considerably higher--0.18 and 0.15, respectively. The EVF of CA1 stratum pyramidale was reversibly reduced by 30 percent when the extracellular potassium concentration was raised from 3.5 to 8.5 mM, a procedure that induced spontaneous electrographic seizures in CA1. Thus there are regional variations in the properties of the extracellular space in the hippocampus that might underlie the propensity of the CA1 region to develop seizures and to suffer damage after ischemia.     

对INT-FAK信号通路调控脑缺血后神经细胞凋亡的思考

脑缺血性疾病是人类健康的主要杀手之一,相关研究表明,神经细胞的凋亡是造成脑缺血疾病中神经系统损害的主要机制之一,而以整合素-黏着斑激酶（INT-FAK）控制调节的PI3K/PDK/Akt以及Raf/MEK/ERK两条主要信号途径引起的细胞凋亡是其主要作用机制。凋亡过程出现的诸多能加以调控的信号分子,都可以作为治疗脑缺血性损伤的潜在靶点。随着对脑缺血损伤与神经细胞凋亡关联的深入研究,抗凋亡治疗已经成为治疗脑缺血性疾病的重要途径。     

NMDA receptor-mediated K+ efflux and neuronal apoptosis

Neuronal death induced by activating N-methyl-D-aspartate (NMDA) receptors has been linked to Ca2+ and Na+ influx through associated channels. Whole-cell recording from cultured mouse cortical neurons revealed a NMDA-evoked outward current, INMDA-K, carried by K+ efflux at membrane potentials positive to -86 millivolts. Cortical neurons exposed to NMDA in medium containing reduced Na+ and Ca2+ (as found in ischemic brain tissue) lost substantial intracellular K+ and underwent apoptosis. Both K+ loss and apoptosis were attenuated by increasing extracellular K+, even when voltage-gated Ca2+ channels were blocked. Thus NMDA receptor-mediated K+ efflux may contribute to neuronal apoptosis after brain ischemia.     

Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart

There is substantial interest in the development of drugs that limit the extent of ischemia-induced cardiac damage caused by myocardial infarction or by certain surgical procedures. Here, using an unbiased proteomic search, we identified mitochondrial aldehyde dehydrogenase 2 (ALDH2) as an enzyme whose activation correlates with reduced ischemic heart damage in rodent models. A high-throughput screen yielded a small-molecule activator of ALDH2 (Alda-1) that, when administered to rats before an ischemic event, reduced infarct size by 60%, most likely through its inhibitory effect on the formation of cytotoxic aldehydes. In vitro, Alda-1 was a particularly effective activator of ALDH2*2, an inactive mutant form of the enzyme that is found in 40% of East Asian populations. Thus, pharmacologic enhancement of ALDH2 activity may be useful for patients with wild-type or mutant ALDH2 who are subjected to cardiac ischemia, such as during coronary bypass surgery.     

奥扎格雷钠对大鼠局灶性脑缺血的保护作用

目的:探讨奥扎格雷钠对大鼠局灶性脑缺血损伤的保护作用。方法:采用大鼠大脑中动脉线栓(MCAO)法制备局灶性脑缺血模型。24只SD雄性大鼠,随机分为假手术组、缺血组和奥扎格雷钠组,假手术组线栓插入颈内动脉深度仅为1 cm,而缺血组和奥扎格雷钠组分别于阻断大脑中动脉后舌静脉注射生理盐水和奥扎格雷钠8 mg/kg。用Longa评分标准对神经系统损伤程度进行评估;TTC染色计算脑缺血体积。结果:与假手术组比较,缺血组大鼠神经系统损伤症状明显,脑缺血体积增大;与缺血组比较,奥扎格雷钠显著改善大鼠的神经系统损伤症状,减少脑缺血体积。结论:奥扎格雷钠对大鼠局灶性脑缺血具有保护作用。     

2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline: a neuroprotectant for cerebral ischemia

2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) is an analog of the quinoxalinedione antagonists to the non-N-methyl-D-aspartate (non-NMDA) glutamate receptor. NBQX is a potent and selective inhibitor of binding to the quisqualate subtype of the glutamate receptor, with no activity at the NMDA and glycine sites. NBQX protects against global ischemia, even when administered 2 hours after an ischemic challenge.     

参附注射液对大鼠心肌缺血再灌注损伤心电图的影响

目的观察参附注射液对大鼠心肌缺血再灌注损伤时ST段和心律失常的影响。方法健康SD大鼠24只随机分为两组,缺血再灌注组（IR组）和参附注射液预处理组（SF组）,每组12只。采用夹闭左冠状动脉30 min,再灌注90min,复制心肌缺血再灌注模型。夹闭前SF组静脉注射参附注射液5 mL/100g进行预处理,观察各组大鼠在整个缺血再灌注期间心电图ST段和心律失常发生情况。结果SF组ST段变化均低于IR组各时间对应值,SF组心肌缺血再灌注后的室性心动过速及心室颤动的发生率均明显低于IR组,差异均有统计学意义（P＜0.01或0.05）。结论参附注射液能降低心肌缺血再灌注损伤程度和室性心律失常发生率。     

Mediation of cardioprotection by transforming growth factor-beta

Myocardial ischemia causes heart injury that is characterized by an increase in circulating tumor necrosis factor (TNF), the local production of superoxide anions, the loss of coronary vasodilation (relaxation) in response to agents that release endothelial cell relaxation factor, and cardiac tissue damage. Ischemic injury can be mimicked by TNF. When given before or immediately after ischemic injury, transforming growth factor-beta (TGF-beta) reduced the amount of superoxide anions in the coronary circulation, maintained endothelial-dependent coronary relaxation, and reduced injury mediated by exogenous TNF. Thus, TGF-beta prevented severe cardiac injury, perhaps by alleviating damage mediated by increases in circulating TNF.     

补阳还五汤对去势脑缺血雌性大鼠海马神经干细胞增殖及ERK/CREB信号通路的影响

目的 探讨补阳还五汤对去势脑缺血雌性大鼠海马神经干细胞（neural stem cells,NSCs）增殖及ERK/CREB信号通路的影响。方法 采用双侧卵巢切除术（OVX）结合大脑中动脉阻塞（MCAO）法复制去势雌性大鼠脑缺血复合模型,将造模后的36只大鼠随机分为双假手术组、复合模型组、雌激素组、雌激素+G15组、补阳还五汤组及补阳还五汤+G15组6组,每组6只,术后24 h给予相应药物灌胃连续干预14 d,同时每天腹腔注射BrdU、G15分别标记增殖细胞和阻断GPER-1。采用免疫荧光BrdU/Nestin双标法检测各组大鼠缺血侧海马齿状回NSCs增殖情况,免疫组化SP法检测ERK1/2、CREB1磷酸化蛋白表达水平。结果 补阳还五汤组和雌激素组缺血侧海马DG区BrdU/Nestin双标阳性细胞及pERK1/2、pCREB1阳性细胞表达均增加,与复合模型组比较有显著性差异（P<0.05）,但补阳还五汤组要多于雌激素组（P<0.05）。与补阳还五汤组比较,补阳还五汤+G15组缺血侧海马DG区BrdU/Nestin双标阳性细胞及及pERK1/2、pCREB1阳性细胞表达均减少（P<0.05）。结论 补阳还五汤可以促进去势脑缺血雌性大鼠缺血侧海马DG区神经干细胞增殖,激活ERK/CREB信号通路,可能是其发挥类雌激素作用、促进内源性神经再生作用机制之一。     

进展性缺血性脑卒中危险因素分析

目的探讨与进展性缺血性脑卒中相关的危险因素.方法查阅近10余年来国内外关于进展性缺血性脑卒中的相关文献,分析与进展性缺血性脑卒中相关因素,为临床防治进展性缺血性脑卒中提供理论依据.结果研究表明：缺血区的脑血流量下降、血压变化、高血糖、发热与感染、脂蛋白与含铁蛋白含量、颈动脉粥样硬化及斑块形成、血浆总同型半胱氨酸水平、血清可溶性细胞间黏附分子1、白细胞流变特性及分子流变特性、血浆内皮素和一氧化氮含量的变化及谷氨酸（Glu）浓度等均与进展性缺血性脑卒中有关.结论与脑卒中进展相关的诸因素可增加致残率,预后差,治疗困难,对这些因素的关注有助于防治进展性缺血性脑卒中.     

丹参地上部分正丁醇萃取部位化学成分检测及其抗脑缺血研究

筛选丹参地上部分抗脑缺血的活性部位,并检测其所含化学成分,对丹参的开发和利用具有重要意义。采用D101大孔吸附树脂吸附丹参地上部分正丁醇萃取部位,将其分离纯化为多个部位。以昆明小鼠常压缺氧模型和不完全性脑缺血模型筛选有效部位;将筛选出的活性部位再用聚酰胺柱分离为不同部位,选用上述模型进行活性部位筛选;并用高效液相检测筛选的活性部位所含化学成分。结果表明:D-101大孔树脂经体积分数为50%和75%乙醇洗脱部位能显著增加小鼠常压耐缺氧时间,延长小鼠全脑缺血后的存活时间(P0.01);聚酰胺柱分离后的水洗部位可显著增加小鼠常压耐缺氧时间和小鼠全脑缺血后的存活时间(P0.01);高效液相检测聚酰胺柱分离的水洗部位含有原儿茶醛、咖啡酸、丹参素。丹参地上部分正丁醇萃取部位聚酰胺柱分离的水洗部位为有效部位,检测出有效成分为原儿茶醛、咖啡酸、丹参素。     

三七皂苷对大鼠缺血脑组织一氧化氮合酶表达的影响——免疫细胞化学与图像分析系统在免疫药理学研究中的应用

应用免疫细胞化学技术与图像分析系统研究三七皂苷的免疫药理学机制。正常组大鼠;实验组大鼠(左颈总动脉结扎并于术前4h肌注三七皂苷,7mg.kg~(-1))与对照组大鼠(左颈总动脉结扎用等量生理盐水取代三七皂苷)各分4h组、12h组与24h组。各组鼠大脑皮质、海马与尾壳核内神经元性一氧化氮合酶(nNOS)的含量用LSAB法与计算机数字图像分析系统检测。结果显示对照组大鼠海马、尾壳核与大脑皮质内nNOS含量显著下降,三七皂苷可恢复缺血脑组织的nNOS表达,并对缺血脑组织发挥保护作用。同时,本实验还提示免疫细胞化学技术与图像分析系统用于免疫药理学研究是可行的。     

噻苯唑抗心律失常的实验观察

用氯化钙致家兔实验性心律失常和大鼠心肌缺血再灌注心律失常模型，观察噻苯唑的抗心律失常作用。结果表明：噻苯唑有较好的抗心律失常作用，其机理可能与对Ｃａ＾２＋转运的影响有关。     

颈动脉内膜切除术治疗缺血性脑血管病的围手术期观察

目的探讨颈动脉内膜切除术(CEA)治疗缺血性脑血管病的适应证及围手术期处理。方法分析13例因短暂性脑缺血发作(TIA)、分水岭脑梗死伴有颈动脉硬化狭窄患者而行CEA的临床资料。结果10例原有的脑缺血症状完全缓解(2例术后1 d拔除橡皮片后出现颈部血肿),其中腔隙性脑梗死4例、分水岭性脑梗死3例、未发现明显脑梗死灶3例;2例术后1周内再次出现TIA症状,但次数比术前明显减少、症状轻微;1例术中出现脑卒中。总有效率92.3%(12/13)。结论CEA是治疗颈动脉严重狭窄所致缺血性脑血管病的一种有效方法,对分水岭脑梗死、TIA疗效尤其明显。     

柴胡三参胶囊对缺血性心律失常大鼠心肌细胞Cx43的影响

目的 探讨柴胡三参胶囊对缺血性心律失常大鼠心肌细胞间缝隙连接蛋白43（connexin 43,Cx43）表达和分布的影响,为柴胡三参胶囊的临床应用提供实验依据。方法 大鼠随机分为空白组、假手术组、模型组、柴胡三参胶囊（青蒿组）、柴胡三参胶囊（常山组）、胺碘酮组、稳心颗粒组,每组各10只。相应干预10 d后,除空白组和对照组外,其余各组采取大鼠左冠状动脉前降支高位结扎法制作心肌缺血性心律失常模型,再用免疫组织化学S-P法检测Cx43蛋白在各组大鼠心肌中的表达水平及分布情况。结果 柴胡三参胶囊（青蒿组）与柴胡三参胶囊（常山组）Cx43免疫组化灰度值比较差异无统计学意义（P>0.05）;与模型组比较,柴胡三参胶囊心律失常评分降低（P<0.05）、死亡率降低、Cx43平均灰度值增高（P<0.05）及分布紊乱得到改善。结论 柴胡三参胶囊（青蒿）与柴胡三参胶囊（常山）均能够改善心肌缺血时Cx43的表达及分布,保护心肌,从而减少缺血性心律失常的发生,且柴胡三参胶囊（青蒿）临床安全性更高。     

多胺代谢与缺血性心血管疾病研究进展

多胺广泛分布于生物组织和体液中,参与体内多种生理和病理过程,具有促进细胞生长、分化、增生,对维持细胞膜和线粒体的完整性,DNA和RNA结构的稳定性,以及在信号转导、基因表达、蛋白合成等方面都意义重大。多胺参与心肌缺血损伤的发生,多胺代谢失衡,鸟氨酸脱羧酶及精脒/精胺乙酰转移酶活性改变,腐胺生成增多而精胺、精脒减少,将导致继发性的心肌损伤,本文就多胺及多胺在缺血性心血管疾病研究中的意义及进展加以综述。     

山葡萄多酚对大鼠缺血再灌注心肌线粒体损伤的保护作用

目的观察山葡萄多酚（PVAR）对大鼠缺血再灌注心肌线粒体损伤的保护作用．方法结扎Wistar大鼠冠状动脉30min再灌注20min,测定心肌线粒体中琥珀酸脱氢酶（SDH）、细胞色素C氧化酶（CCO）和SOD活性,膜磷脂及MDA含量．结果与模型组比较,PVAR（200,400mg／kg）组SDH,CCO,SOD活性明显升高（P〈0．05）,膜磷脂含量增加（P〈0．05）,MDA含量降低（P〈0．05）．结论PVAR对缺血再灌注损伤的心肌线粒体功能具有保护作用．