Augmentation of nitrite therapy in cerebral ischemia by NMDA receptor inhibition

Our recent work suggested that early infusion of nitrite might represent a novel therapeutic approach for acute ischemic stroke. In this study, we sought to examine the therapeutic time window of nitrite in an experimental stroke model, and to develop combined strategies for augmenting its protective effects. Nitrite was infused at various times after ischemia to rats subjected to transient or permanent focal ischemia. Nitrite was infused with memantine to prevent the potential toxicity. Infarct volumes, functional outcomes, microhypoxic areas, and oxidative stress were measured. Nitrite reduced the infarction volume and enhanced functional recovery when administered within 3 and 1.5 h in the transient and permanent model, respectively. Combined therapy with nitrite and memantine prolonged the time window up to 4.5 h. The potential oxidative toxicities of nitrite were significantly inhibited by memantine. The combination therapy of nitrite and memantine may be a feasible therapeutic approach for acute ischemic stroke.     

Tolerated nitrite therapy in experimental intracerebral hemorrhage: Rationale of nitrite therapy in a broad range of hyperacute strokes

Nitrite therapy is more effective in cerebral ischemia when administered earlier. It would be beneficial during the hyperacute stages of stroke if the nitrite effect is demonstrated in intracerebral hemorrhage (ICH). When nitrite is injected intravenously 3 h after ICH induction in rats, most doses of nitrite provided no beneficial effects on behavioral deficits, brain edema and hematoma volumes. A high dose of nitrite, however, decreased hematoma volume, but not brain edema. Peri-hematomal apoptosis and inflammation were similar between the control and nitrite groups. Nitrite therapy may be considered a therapeutic option in hyperacute stroke because nitrite therapy is tolerated in ICH as well.     

活性氧簇在脑缺血-再灌注损伤中的损伤与保护作用

活性氧簇是细胞有氧代谢过程中产生的一类化学基团。线粒体是活性氧簇的主要生成位点。一般观点认为,在脑缺血-再灌注损伤过程中,活性氧簇发挥神经细胞损伤作用。活性氧簇不仅直接参与神经细胞氧化损伤过程,也可通过外源性途径和内源性途径,引起神经细胞凋亡。然而,除神经细胞损伤作用外,活性氧簇也可发挥神经细胞保护作用。活性氧簇可激活低氧诱导因子、核转录因子κB、PI3K/Akt通路和MAPK通路等,参与神经细胞存活机制,减轻神经细胞损伤。本文对活性氧簇在脑缺血-再灌注损伤中的双重作用进行综述。     

Synaptosomal glutamate uptake in a model of experimental cerebral ischemia

In the present investigation we studied the synaptosomal uptake of glutamate in brain omogenate of Mongolian gerbils submitted to bilateral common carotid occlusion, with and without subsequent return of blood flow. The results show that glutamate uptake after ischemia is reduced by about 35% The damage appears to be persistent, since return of blood flow restores uptake only slightly. The membrane alterations occurring in ischemia could explain the persistence of glutamate transporter impairment. Besides the blockade of NMDA receptors, the stimulation and/or the protection of the uptake systems for glutamate could be of help in preventing neuronal ischemic damage.     

活性氮自由基:脑缺血再灌注损伤过程中引起血脑屏障破坏及调节神经修复的双刃剑(英文)

在脑缺血再灌注损伤中,自由基发挥着重要作用。脑缺血及再灌注可产生大量的自由基,随着这些自由基的聚集,会引发一系列的分子级联反应,从而增加血脑屏障的通透性,诱发脑水肿、出血、炎症反应及细胞死亡。以一氧化氮(NO)及过氧亚硝基阴离子(ONOO-)为代表的活性氮(reactive nitrogen species,RNS),是自由基的重要组成部分,它们在脑缺血再灌注损伤中作用显著。一方面,活性氮能激活基质金属蛋白酶(MMPs),破坏血脑屏障。MMPs作为一大类含2价锌离子的水解酶,其激活可以降解脑血管及神经元细胞外基质。脑缺血再灌注损伤产生NO和ONOO-,它们均可以通过激活MMPs,降解紧密连接蛋白,从而破坏血脑屏障。另一方面,近期研究发现,活性氮也参与了脑缺血后神经再生及修复的调节过程。因此,了解这些活性小分子在血脑屏障破坏及神经再生中的复杂生物活性将很有意义。小窝蛋白1(Caveolin-1)就是活性氮自由基的重要靶分子,它是一种细胞表面的穴样内陷(caveolae)中的膜蛋白,可以通过抑制MMPs的激活保护血脑屏障的完整性。下调Caveolin-1的表达将引起血脑屏障的破坏。脑缺血所产生的NO能下调Caveolin-1的表达,而Caveolin-1的下调,能引起NO合酶的增加,促进生成更多的NO。活性氮与Caveolin-1互相作用,形成了一个反馈回路,通过激活MMPs而造成血脑屏障的不断破坏。此外,Caveolin-1通过调节不同的信号通路,抑制神经干细胞的增长及向神经元分化。因此,活性氮也很可能通过调节Caveolin-1及其他信号通路调控神经再生。在这篇文章中,我们对活性氮在血脑屏障及神经再生中的近期研究进展进行了综述。我们认为,活性氮可能在脑缺血再灌注中起双重作用,既是细胞毒性分子,亦可能是神经再生中的重要信号分子,其作用与其在神经元、内皮细胞及其微环境中产生的量有重要的关系。     

异丙酚对家兔肝缺血/再灌注后抗氧化能力改变的影响

目的: 探讨氧自由基(OFR)在肝缺血/再灌注损伤(HI/RI)中的作用及异丙酚对其的影响.方法: 实验兔随机分为假手术对照组、肝缺血/再灌注组和肝缺血/再灌注加异丙酚治疗组,分别在肝缺血前、缺血45 min、再灌注45 min共3个时相点,检测血浆及肝组织超氧化物歧化酶(SOD)活性、黄嘌呤氧化酶(XO)活性、丙二醛( MDA)浓度及谷丙转氨酶(ALT)值,并行肝组织电镜观察.结果: 肝缺血/再灌注期间,血浆XO、MDA及ALT显著高于、SOD明显低于假手术对照组(P<0.05和P<0.01);肝组织XO及MDA显著高于、SOD明显低于假手术对照组(P<0.05和P<0.01);肝组织超微结构发生异常改变.异丙酚可逆转上述指标的异常变化,与肝缺血/再灌注组相比有显著性差异(P<0.05和P<0.01).结论: OFR在HI/RI发生发展中起介导作用;异丙酚可通过降低氧自由基水平(增强SOD活性、减弱XO活性),拮抗脂质过氧化反应(降低MDA浓度),从而减轻HIRI.     

VEGF 对大鼠脑缺血再灌注损伤的预防作用及其机制研究

目的:研究局灶性脑缺血再灌注后细胞凋亡、HSP70蛋白表达时空规律以及外源VEGF及VEGF抗体对它们的影响,探讨VEGF对缺血再灌注损伤的保护作用及其机制.方法:采用原位末端标记(TUNEL)、免疫组化方法,研究局灶性脑缺血再灌注后细胞凋亡数及HSP70蛋白表达时空分布,采用脑表面使用VEGF及侧脑室注射VEGF抗体,观察内外源VEGF对它们的影响.结果:VEGF抗体能显著增加缺血侧脑组织凋亡细胞数(再灌注12h-7d)及HSP70表达量(再灌注1-3d),而外源VEGF因子能显著减少同侧脑组织凋亡细胞(再灌注全程)及HSP70表达量(再灌注1-3d).结论:VEGF因子可抑制缺血脑组织细胞凋亡及HSP70表达量,提示VEGF参与保护缺血性脑损伤.     

熊果苷对小鼠脑缺血再灌注损伤的影响

目的：本研究旨在探讨中药熊果苷对缺血再灌注损伤后脑细胞的影响,为中药熊果苷的临床应用提供理论依据。方法：昆明种小鼠40只,随机分成4组,即空白组、模型组、药物预防组和药物治疗组。根据缺血时脑损伤原理制成脑缺血再灌注损伤模型,以TTC染色、HE染色观察细胞形态学变化,并检测脑组织中超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量及谷胱甘肽过氧化物酶（GSH-Px）活性的变化。结果：与模型组相比,药物预防组和药物治疗组分别TTC染色缺血区域都不如模型组坏死明显,HE染色显示细胞损伤程度减轻,SOD、GSH—Px活性提高有显著性差异,MDA含量减少（均P〈0．05）。结论：药物熊果苷具有抗氧化作用,能有效地预防和保护脑细胞损伤。     

蒙药绍沙-7味丸防治大鼠心肌缺血/再灌注损伤的作用

目的:探讨蒙药绍沙-7味丸对心肌缺血/再灌注损伤大鼠的防治作用及机制.方法:60只大鼠随机分成6组:假手术组、模型组、蒙药绍沙-7味丸低、中、高剂量组以及阳性药对照组,每组10只;蒙药绍沙-7味丸低、中、高剂量组分别灌胃0.4 g/kg、0.8 g/kg、1.6 g/kg蒙药绍沙-7味丸,阳性药对照组灌胃0.3 g/k...     

十六酰胺乙醇对大鼠脑缺血再灌注损伤的抗氧化及抗凋亡作用

目的:探讨十六酰胺乙醇(Palmitoylethanolamide PEA)对大鼠脑缺血再灌注损伤的保护作用及机制。方法:将雄性SD大鼠随机分为:假手术组、药物组、模型组。采用线栓法制造大脑中动脉缺血再灌注模型,药物组于缺血后30分钟及再灌注后2小时给予PEA(10mg/Kg)腹腔注射。于再灌注24h后,对各组大鼠进行神经功能评分,TTC染色法测脑梗死体积,硫代巴比妥法测丙二醛(MDA)含量,黄嘌呤氧化酶法测超氧化物歧化酶(SOD)活性,WesternBlot法测Bcl-2和Bax蛋白含量。结果:药物组神经功能评分均值为1.33±0.49分,而模型组为2.20±0.41分,药物组神经功能评分显著低于模型组(P0.05);药物组的脑梗死体积为114.00±8.63mm3,而模型组脑梗死体积为243.40±14.19mm3,药物组脑梗死体积显著低于模型组(P0.05);药物组MDA含量为3.85±0.29nmol/mgprot,SOD活性为13.95±0.71U/mgprot,而模型组MDA含量为4.85±0.30nmol/mgprot,SOD活性为12.44±0.40U/mgprot,与模型组相比,药物组的MDA含量显著降低,而SOD活性显著增高(P0.05);药物组Bcl-2蛋白与β-action蛋白的IOD值比值为0.53±0.013%,Bax蛋白与β-action蛋白的IOD值比值为0.54±0.012%,模型组Bcl-2蛋白与β-action蛋白的IOD值比值为0.40±0.012%,Bax蛋白与β-action蛋白的IOD值比值为0.80±0.012%。药物组Bax蛋白含量显著低于模型组(P0.05),而Bcl-2蛋白含量显著高于模型组(P0.05)。结论:PEA对大鼠脑缺血再灌注损伤具有保护作用,可能是通过抗凋亡、抗氧化应激等作用实现。     

Effect of Sargentodoxa cuneata total phenolic acids on focal cerebral ischemia reperfusion injury rats model

Objective

Explore the possible protective effect of Sargentodoxa cuneata total phenolic acids on cerebral ischemia reperfusion injury rats.

亚硝氮对海洋着色菌亚硝氮和氨氮去除以及光合色素合成的影响

【目的】在以亚硝氮为唯一氮源和亚硝氮-氨氮共存体系中,考察和分析海洋着色菌(Marichromatium gracile) YL28菌株对水体亚硝氮的环境适应能力。【方法】采用分光光度法分析亚硝氮、氨氮去除效率以及亚硝氮对菌体生物量和色素含量的影响,采用薄层层析法分析亚硝氮对菌体光合色素组成的影响。【结果】YL28菌株能以亚硝氮为唯一氮源生长,主要积累2种细菌叶绿素(BChl)组分(BChl aTHGG和BChl ap)、1种细菌脱镁叶绿素(Bphe)和玫红品(Rhodopin)、螺菌黄质(Spirilloxanthin)、脱水紫菌红醇(Anhydrorhodovibrin)、番茄红素(Lycopene) 4种类胡萝卜素(Car);YL28生物量和对亚硝氮的去除效率随亚硝氮浓度升高而降低,完全去除亚硝氮的浓度可达200 mg/L以上;当亚硝氮浓度高于25 mg/L,单位质量菌体BChl a和Car总量降低,BChl a和Car合成的末端产物(BChl ap和Spirilloxanthin)以及Bphe相对含量升高,其它4种色素组分相对含量则降低,但Car与BChl a相对含量的比值未见明显变化。当亚硝氮-氨氮共存时,YL28菌株对亚硝氮的耐受能力和去除能力明显提高,完全去除亚硝氮的浓度可达300 mg/L以上;氨氮减缓了亚硝氮对光合色素合成的抑制作用,提高了菌体色素合成总量,各色素组分相对含量的变化与亚硝氮为唯一氮源时的变化规律一致。【结论】YL28菌株能高效去除亚硝氮,亚硝氮对菌株生长和光合色素的合成有抑制作用,但氨氮能明显提高YL28菌株对亚硝氮的适应能力。这为进一步开发高效脱除亚硝氮的APB水质调节剂奠定了基础。     

植入血管束的血管化人工神经导管对受损神经功能恢复影响的实验研究

目的:研究植入血管束的血管化人工神经导管修复SD大鼠长段坐骨神经缺损对神经功能恢复的影响。方法:将18只成年雌性SD大鼠制成14mm的大鼠坐骨神经缺损模型后,随机分为3组(每组12条神经),分别采用不同的修复方法。A组:自体神经移植组(自体组);B组:普通PGLA神经导管移植组(导管组);C组:植入自体血管束的普通PGLA神经导管移植组(血管化导管组)。观察术后大鼠后肢皮肤溃疡面积;检测术后6周、12周时步态变化和肌电图。结果:术后各组SD大鼠均出现后肢溃疡,血管化导管组SD大鼠后肢溃疡愈合较导管组早2周。血管化导管组步态检测SFI明显优于导管组,与自体神经移植组无明显差异。肌电图检测表明血管化导管组无论是神经传导速度,还是动作电位振幅均明显大于导管组(P<0.05),与自体神经移植组无明显差异(P>0.05)。结论:植入血管束的血管化人工神经导管能有效地促进受损神经的功能恢复。     

腌制肉中亚硝酸盐抑菌机理的研究进展

亚硝酸盐是内制品中常用的食品添加剂,具有发色、抑菌、改善风味和质构等作用,特别是亚硝酸盐能够有效的防止内毒梭状杆菌的生长,但是亚硝酸盐具有毒性,亚硝酸根与肉类中的胺类物质反应生成致癌物亚硝胺,使亚硝酸盐的使用受到限制。已有许多亚硝酸盐抑菌机理的研究报道,本文综述了亚硝酸盐作用的微生物、腌制成分和其它因素对亚硝酸盐押菌作用的影响、以及亚硝酸盐抑菌分子机理的研究进展,并对亚硝酸盐作用机理的研究方向进行了展望。     

神经调节素对大鼠脑缺血再灌注损伤后炎症反应的抑制作用和机制研究

目的：研究神经调节素及基质金属蛋白酶-9对于小鼠大脑缺血再灌注损伤后炎症反应的抑制作用和机制。方法：选取100只成年雄性大鼠,随机分成对照和治疗组。采用线栓方法由颈内到颈外进行插线处理,造成大脑中动脉处于闭塞状态的再灌注动物模型。治疗组颈动脉进行注射少量NRG-1β干预性治疗,通过氯化三苯基四氮唑（TTC）检查脑梗塞范围,细胞凋亡采用原住脱氧核糖核苷酸末端转移酶介导缺口末端进行标记,采用免疫组织化学、免疫荧光双标记法及免疫印迹法观察脑组织基质金属蛋白酶-9（MMP-9）表达。结果：脑缺血再灌注损伤后,随时间延长及缺氧,对照组大鼠大脑皮质和纹状体区脑组织细胞凋亡,并且胶质细胞MMP-9蛋白表达逐渐增加。治疗组大鼠经注射NRG-1β干预性治疗后,缺血脑组织梗死范围及其细胞凋亡数量相对呈明显下降趋势。胶质细胞MMP-9表达呈降低趋势。结论：大鼠脑缺血再灌注损伤后体内NRG-1β抑制胶质细胞MMP-9的表达,控制缺血脑组织梗死的范围并抑制正常细胞的凋亡,发挥了重要的抗炎作用,可作为对于大脑缺血再灌注损伤的研究新靶点。     

海藻糖的长期毒性试验研究

海藻糖是一种由两分子葡萄糖缩合而成的非还原性二糖,它作为生物制品、医药及食品的保护剂和添加剂,已在国内外许多文献中报道。本文通过对大白鼠的长期毒性试验研究,表明海藻糖对人体无潜在危害,是安全的。     

Nonthermal effect of microwave irradiation on nitrite uptake in Chlamydomonas reinhardtii

When cells of the unicellular green alga Chlamydomonas reinhardtii were subjected to microwave irradiation at 2.45 GHz, nitrite uptake kinetics still obeyed the Michaelis-Menten equation, the Km of the process remaining constant, whereas V _max increased, which indicates an enhanced nonthermal permeability in irradiated cells.     

The protective role of verbenalin in rat model of focal cerebral ischemia reperfusion

To investigate the protective mechanism of verbenalin on cerebral ischemia-reperfusion injury. Middle cerebral artery occlusion in the left hemisphere was induced in rats by filament insertion, and rat model of focal cerebral ischemia-reperfusion was established. The high, medium and low dose of verbenalin groups were injected in the tail vein of corresponding drugs 10?min before reperfusion, and submitted for 22?h of reperfusion after the operation. Mortality rate was then calculated, and neurological deficits of rats were scored. The serum of rats was got to determine the S-100β protein level, and the brain tissue was removed to determine the levels of Bax, Bcl-2, Caspase-3 and ATPase. TTC staining was performed on the brain tissue to calculate the percentage of cerebral infarct size. Changes in brain tissue morphology were observed. Rat model of focal cerebral ischemia-reperfusion was successfully replicated. In groups that have taken different doses of verbenalin, the mortality rate, neurological deficit score and the percentage of cerebral infarction size were significantly reduced, and the levels of Bax, Caspase-3, S-100β level of the serum in the brain tissue were also significantly reduced. Increases in the levels of Bcl-2 and ATPase in brain tissue and improvement of pathological damage of hippocampus and cortex were observed. Verbenalin can inhibit the expression of apoptosis genes, promote the expression of anti-apoptosis genes, improve brain microcirculation and energy metabolism, hence reducing cerebral ischemia-reperfusion injury.     

慢性阻塞性肺疾病患者家庭长期氧疗的临床研究

目的：探讨家庭长期氧疗（LTOT）对慢性阻塞性肺疾病（COPD）患者的疗效。方法：将我院同期住院病人随机分为LTOT组（51人）,对照组（52人）。全部病例在缓解期及治疗后每年测定PaO2、PaCO2、FVC、FEV1、HB、HCT的数值及每年住院次数。结果：①氧疗后1、2、3、4、5年与氧疗前比较,低氧血症改善,FEV1明显提高,HB、HCT明显减少;每年住院次数减少;②LTOT组5年生存率62．75％,对照组5年生存率46．15％,差异有显著性（p〈0．05）。结论：合理使用LTOT对COPD患者有良好的治疗作用,可提高患者的5年生存率。     

Effects of temperature on simultaneous nitrification and denitrification via nitrite in a sequencing batch biofilm reactor

A laboratory scale experiment was described in this paper to enhance biological nitrogen removal by simultaneous nitrification and denitrification (SND) via nitrite with a sequencing batch biofilm reactor (SBBR). Under conditions of total nitrogen (TN) about 30 mg/L and pH ranged 7.15–7.62, synthetic wastewater was cyclically operated within the reactor for 110 days. Optimal operation conditions were established to obtain consistently high TN removal rate and nitrite accumulation ratio, which included an optimal temperature of 31 °C and an aeration time of 5 h under the air flow of 50 L/h. Stable nitrite accumulation could be realized under different temperatures and the nitrite accumulation ratio increased with an increase of temperature from 15 to 35 °C. The highest TN removal rate (91.9%) was at 31 °C with DO ranged 3–4 mg/L. Process control could be achieved by observing changes in DO and pH to judge the end-point of oxidation of ammonia and SND.