熊果酸对人外周血单个核细胞分泌Th1/Th2型细胞因子的影响

目的 观察熊果酸对植物血凝素(phytohaemagglutinin,PHA)活化的人外周血单个核细胞分泌Th1/Th2型细胞因子的影响.方法 无菌分离外周血单个核细胞后于细胞悬液中加入熊果酸(终浓度为20 μmol/L,40 μmol/L和60 μmol/L)和PHA(5 μg/ml)培养24 h和48 h,用ELISA法检测细胞培养上清中Th1型细胞因子(TNF-α、IFN-γ、IL-2)和Th2型细胞因子(IL-4)浓度的改变.结果 熊果酸可呈浓度依赖性地抑制TNF-α、IFN-γ、IL-2的分泌,以40 μmol/L和60 μmol/L的效果最为显著,而20 μmol/L的抑制作用相对较弱.熊果酸对IL-4的抑制作用不明显,仅出现在60 μmol/L组.结论 熊果酸可显著抑制Th1型细胞因子的分泌,高浓度时亦能抑制Th2型细胞因子,借此发挥其免疫调节功能.     

(英文)肾移植患者血清非对称二甲基精氨酸水平变化与内皮功能改善的关系

目的:探讨肾移植前后慢性肾衰患者血清非对称二甲基精氨酸(ADMA)水平变化与内皮功能改善的关系.方法:选择首次接受同种异体肾移植术患者38例和健康对照者36例.分别于移植术前、移植术后第1,3,7,14及28天抽血分离血清,高效液相色谱法(HPLC)检测血清ADMA和SDMA水平,硝酸还原酶比色法检测血清NO活性,DTNB法测定全血硒谷胱甘肽过氧化物酶 (SeGSHPx)活性,,硫代巴比妥酸法测定血清丙二醛(MDA)水平,ELISA法检测血清C反应蛋白(CRP)水平;移植术前及术后第28天多普勒超声法检测肱动脉内皮依赖性血管舒张功能(FMD).结果:肾移植术前患者血清ADMA[(2.36±0.89) μmol/L],SDMA[(0.48±0.11) μmol/L],MDA[(7.24±1.07) μmol/L]及CRP水平[9.24(0.42～66.24) μmol/L]明显高于年龄匹配的正常对照组[ADMA:(0.49±0.12) μmol/L;SDMA:(0.24±0.08) μmol/L;MDA:(3.12±1.21) μmol/L;CRP:2.52(0.24～5.94) μmol/L, 均P＜0.01],血清NO[(38.48±12.36) μmol/L] 及SeGSHPx[(104.23±14.46) U/L]活性、FMD(5.43%±1.87%)明显低于正常对照组 [NO:(70.13±12.46) μmol/L;SeGSHPx:(201.36±82.35) U/L;FMD:(10.11±1.64)%,均P＜0.01].移植术后第1天开始血清ADMA[(1.97±0.76) μmol/L],SDMA[(0.43±0.06) μmol/L],MDA[(6.24±0.82) μmol/L]及CRP[8.32(0.46～33.42) μmol/L]水平明显下降而血清NO[(42.63±11.32) μmol/L],SeGSHPx[(116.23±17.24) U/L]活性明显增高,第28天时除SDMA水平与对照组无差别外(P＞0.05),其余指标仍高于或低于正常对照组(P＜0.05).第28天时FMD(7.04±2.13)%较移植前明显增高但仍低于正常时对照组(P＜0.05).移植前后血清ADMA水平与MDA呈正相关,与SeGSHPx及FMD呈负相关.结论:慢性肾衰患者移植前后血清ADMA水平变化与内皮功能异常关系密切,并与氧化应激程度相关.     

白藜芦醇对难治性癫痫细胞模型神经元损伤及神经突起的影响

目的 探讨白藜芦醇(Res)对难治性癫痫细胞模型的神经元损伤及神经突起形态学变化的影响.方法 将体外培养至第10天的大鼠乳鼠海马神经元分为对照组、模型组、10 μmol/L Res组、20 μmol/L Res组、40 μmol/L Res组及60 μmol/L Res组.对照组采用正常细胞的细胞外液培养3h后恢复维持培养液,模型组采用无镁细胞外液培养3h后恢复维持培养液,4个Res组经无镁细胞外液培养3h后加入相应浓度的Res培养液.检测建立模型后24 h各组细胞上清液乳酸脱氢酶(LDH)的活性,光学显微镜下观察各组神经元及神经突起的形态学变化.结果 与对照组相比,模型组及各浓度Res组的LDH活性显著增加(P＜0.05);与模型组相比,10 μmol/L、20 μmol/L、40 μmol/L Res组LDH活性明显降低(P＜0.05),其中以40 μmol/L Res组最低;60 μmol/L Res组与模型细胞的LDH活性比较,差异无统计学意义(P＞0.05).经建立模型后24 h,光学显微镜下可见模型组神经突起之间相互迁移聚集,突起连接成“网格样”;40 μmol/L Res组出现少部分神经突起迁移靠近聚集,大部分的突起连接分布均匀.结论 Res能减少难治性癫痫细胞模型的神经元损伤,抑制异常神经突起连接的形成.     

男性不育患者精浆NO的含量对生精细胞凋亡的影响

目的:探讨在男性不育中精浆NO含量对生精细胞凋亡的影响.方法:应用硝酸还原酶法测定80例男性不育患者和62例正常有生育能力的健康男性(正常对照)精浆NO的含量;应用TdT介导的原位末端标记法检测15例男性不育患者、12例精浆NO的含量超过135 μmol/L的不育患者和15例正常健康男性的生精细胞凋亡情况;电镜观察不育患者生精细胞凋亡的超微结构变化.结果:不育组与正常对照组精浆 NO含量分别为(107.8±25.9)和(76.5±16.4) μmol/L,差异极显著(t=8.34,P<0.01);15例正常生育组精浆NO含量为(76.7±10.4) μmol/L,生精细胞凋亡率为(3.8±1.3)%;15例不育组NO含量为(112.7±14.3) μmol/L,生精细胞凋亡率为(4.7±1.9)%;12例不育组精浆NO含量高(>135 μmol/L)者的生精细胞凋亡率为(16.3±4.0)%.不育组精浆NO含量和生精细胞的凋亡率均高于正常对照组(P<0.05).不育组精浆NO含量超过135 μmol/L者的生精细胞凋亡率与正常对照组比较两者差异极显著(P<0.01).电镜观察发现,不育患者生精细胞出现核染色质浓缩、电子密度升高、核膜折叠、核裂解、形成凋亡小体等一系列变化.结论:NO含量异常升高使生精细胞凋亡增加而降低生育能力.     

肾上腺髓质素原N端20肽对血管紧张素刺激心肌成纤维细胞生成NO的影响

目的探讨肾上腺髓质素原N端20肽(PAMP)对血管紧张素II刺激心肌成纤维细胞(CFs)生成NO的影响及意义。方法采用胰酶消化、差速贴壁法培养新生SD大鼠CFs,以硝酸还原法测定细胞培养液中NO的浓度,分别观察不同浓度AngII、PAMP、及AngII PAMP对CFs生成NO的影响。结果(1)10-9、10-8、10-7、10-6μmol/LAngII组细胞培养液中的浓度是:(73.88±2.23)、(64.34±3.02)、(54.12±2.82)、(40.21±1.45)μmol/L,各组之间有显著性差异(P<0.01)。(2)10-9、10-8、10-7、10-6μmol/LPAMP组细胞培养液中NO的浓度分别为(74.40±3.42)、(74.91±2.66)、(75.77±3.31)、(74.23±2.43)μmol/L,而空白组为(74.57±2.49)μmol/L。各组之间无显著性差异(P>0.05)。(3)10-7μmol/LAngII (10-9、10-8、10-7、10-6μmol/L)PAMP组培养液中NO合成浓度分别为(66.15±2.95)、(80.58±3.77)、(88.67±1.46)、(96.22±2.96)μmol/L,各组间有显著性差异(P<0.01)。结论随AngⅡ浓度增加可显著抑制CFs分泌NO,而PAMP对CFS合成NO无明显影响,但PAMP与AngII共同培养时,随PMAP浓度增加,NO的合成呈依从性增多。     

L-精氨酸对接振家兔外周血管功能保护作用的研究

目的探讨L 精氨酸对后肢接振家兔外周血管功能的保护作用及意义。方法将家兔随机分为单纯接振组 (A组 ) ,L 精氨酸组 (B组 )和对照组 (C组 ) ,并进行接振试验。从试验第 11天起 ,每隔 2d给予B组L 精氨酸 2 0mg/kg ,分别测定各组血浆一氧化氮 (NO)、内皮素 (ET)浓度进行测定分析。结果试验前及试验后第 10天、2 0天、3 0天 ,A组NO浓度分别为 ( 172 .40 0± 12 .3 5 0 ) μmol/L、( 167.915± 7.879) μmol/L、( 15 0 .0 88± 7.45 3 ) μmol/L、( 13 2 .3 13± 8.747) μmol/L ,ET浓度分别为 ( 4 3 .5 75±8.166) μg/L、( 4 6.2 13± 5 .44 8) μg/L、( 5 3 .788± 6.0 3 7) μg/L、( 66.613± 9.485 ) μg/L ;B组浓度分别为 ( 172 .85 0± 13 .3 2 3 ) μmol/L、( 167.788± 10 .5 3 1) μmol/L、( 164 .12 5± 8.3 80 ) μmol/L、( 161.813± 7.63 9) μmol/L ,ET浓度分别为 ( 4 3 .5 13± 4.90 1) μg/L、( 4 7.175± 7.481) μg/L、( 4 7.0 2 5± 5 .0 2 6) μg/L、( 4 7.60 0± 4.883 ) μg/L。随接振时间延长 ,A组NO浓度有明显降低、ET浓度有明显升高趋势 (P <0 .0 1) ;B组也有类似变化 ,但变化幅度较小。结论L 精氨酸可通过影响接振家兔血管内皮活性物质而保护外周血管功能。     

柴胡皂苷d对SH-SY5Y细胞一氧化氮及JNK磷酸化水平的影响

目的 初步探讨不同浓度的柴胡皂苷d(SSd)对SH-SY5Y细胞一氧化氮(NO)及JNK磷酸化水平的影响.方法 体外培养人神经母细胞瘤SH-SY5Y细胞,将SSd溶解于DMSO中,并分别以0～10μmol/LSSd作用于SH-SY5Y细胞48 h,NO试剂盒检测不同浓度的SSd对SH-SY5Y细胞培养基中NO含量的影响,Western blot法检测细胞中t-JNK、p-JNK蛋白表达水平的变化.结果 与对照组相比,4～10 μmol/L SSd作用48 h,细胞培养基中NO浓度明显减少,其中4μmol/L SSd组细胞培养液中NO含量最低(P＜0.05);而与对照组相比,4～10 μmol/L SSd预处理的SH-SY5Y细胞中p-JNK/t-JNK蛋白表达量比值明显升高,且10 μmol/L SSd组比值最高(P＜0.01).结论 一定浓度的SSd可引起SH-SY5Y细胞NO表达量减少和JNK蛋白磷酸化水平明显升高.     

槲皮素对宫颈癌细胞C33A增殖和凋亡的影响

目的 观察槲皮素对人宫颈癌细胞C33A增殖和凋亡的影响,初步探讨其相关作用机制.方法 用不同浓度槲皮素(空白对照、20、40、80 μmol/L),顺铂(空白对照、5、10、15、20 μg/mL)以及两者联合(槲皮素40 μmol/L+顺铂10 μg/mL)分别作用于C33A细胞24 h和48 h后,噻唑蓝(MTT法)检测细胞活力的变化;流式细胞术检测槲皮素对C33A细胞周期的影响;Western blot检测槲皮素对C33A细胞Cyclin D1、Caspase-3和Caspase-9蛋白表达的影响.结果 MTT结果显示,经过槲皮素处理24 h后,各组细胞活力分别为86.92 ±3.953)%(20 μmol/L组)、(66.54 ±3.932)%(40 μmol/L组)和(52.21 ±2.970)%(80 μmol/L组),均低于空白对照组的(98.35 ±1.230)%;经过槲皮素处理48 h后,各组细胞活力分别为(65.19 ±7.071)%(20 μmol/L组)、(47.04 ±8.881)%(40 μmol/L组)和(29.71 ±6.505)%(80 μmol/L组),均低于空白对照组的(96.97 ±1.788)%.;此外,槲皮素40 μmol/L+顺铂10 μg/mL联合作用于C33A细胞24h后,细胞活力下降为(31.12 ±2.835)%;48 h后,细胞活力下降为(17.86 ± 3.182)%,同空白对照组相比均出现了明显的下降,(31.12 ±2.835)%;48 h后,细胞活力下降为(17.86 ±3.182)%(P<0.05).细胞周期检测结果显示,槲皮素可增加C33A细胞G0/G1期数量,减少S期数量.Western blot 结果显示,槲皮素可下调C33A细胞Cyclin D1蛋白的表达,还可上调Caspase-3和Caspase-9蛋白的表达.结论 槲皮素通过下调Cyclin D1蛋白的表达可以抑制C33A细胞的活力和增殖,槲皮素通过上调Caspase-3和Caspase-9蛋白的表达,可以诱导C33A细胞的凋亡.     

大鼠生精细胞体外培养条件的研究

目的:寻找一个最适合生精细胞体外培养的培养体系,为进一步培养人类生精细胞提供技术基础.方法:用单一酶-研磨-Percoll法制备15 d龄雄性大鼠生精细胞混悬液用于体外培养.①设计两种不同的培养条件:DMEM/F12和改良人类输卵管液(HTF)作为基础培养液,分为两组.每组根据添加不同浓度的激素分为6小组.添加的睾酮(T)和FSH浓度分别为:对照组H0(T 1 μmol/L,FSH 0 IU/L)、H1组(T 1 μmol/L,FSH 10 IU/L)、 H2组(T 1 μmol/L,FSH 25 IU/L)、H3组(T 1 μmol/L,FSH 50 IU/L)、H4组(T 1 μmol/L,FSH 100 IU/L)、H5组(T 0 μmol/L,FSH 50 IU/L). ②通过BRDU标记和流式细胞仪检测所有实验的生精细胞倍体的变化来判断其发育,进一步确认本研究使用培养条件的可靠性.结果:在生精细胞与支持细胞共培养过程中以改良人类输卵管液作为基础培养液,添加T 1 μmol/L ,FSH 50 IU/L或100 IU/L都适宜生精细胞体外培养;另通过BRDU标记及流式细胞仪检测均表明,在本研究条件下体外培养生精细胞能从初级精母细胞阶段分化到精子细胞阶段.结论:改良人类输卵管液作为基础培养液,添加浓度为50 IU/L或100 IU/L的FSH及T 1 μmol/L,最适合生精细胞的体外成熟培养.     

转化生长因子-β1抗体对体外培养肝星状细胞内皮素和一氧化氮的影响

目的:研究转化生长因子-β1 (TGF-β1)抗体对肝星状细胞(HSC)分泌一氧化氮(NO)和内皮素-1(ET-1)的影响. 方法: HSC以1×108/L的密度接种于细胞培养皿中,37℃,50 mL/L CO2条件下培养24 h进行以下分组实验,每组重复4个培养皿:① HSC空白对照组;② HSC TGF-β1抗体. TGF-β1抗体为5～20 mg/L,继续培养24 h. 取培养上清液,用硝酸还原酶法测定NO水平,化学比色法测定一氧化氮合成酶(NOS)活性,酶联免疫吸附(ELISA)双抗体夹心法检测ET-1含量. 结果: TGF-β1抗体能明显抑制HSC分泌ET-1,且随着抗体剂量的增加ET-1含量降低,对照组、10,15 mg/L TGF-β1抗体组分别为(8.50±0.46),(5.33±0.27), (3.69±0.33)μg /L,且各剂量组之间两两比较差异均有统计学意义(P＜0.05);随着TGF-β1抗体剂量加大,iNOS活性和NO的合成增加,对照组,10,15 mg/L TGF-β1抗体组分别为(1.94±0.16),(3.29±0.42),(3.88±0.32) ku/L和(46.75±4.72), (80.68±5.44), (88.58±2.84) μmol/L. 结论: TGF-β1抗体能降低HSC ET-1水平,增加NO含量.     

反复热性惊厥过程中γ-氨基丁酸B受体对一氧化氮/一氧化氮合酶体系的调节作用

目的:探讨γ-氨基丁酸B受体(γ-aminobutyric acid B receptor,GABABR)对热性惊厥(febrile seizure,FS)大鼠一氧化氮(nitric oxide,NO)/一氧化氮合酶(nitric oxide synthase,NOS)体系表达的影响.方法:将21 d龄SD大鼠随机分为对照组、FS组、FS+巴氯芬(baclofen)组和FS+法克罗芬(phaclofen)组.采用热水浴诱导大鼠FS,隔日诱导1次,共10次.采用分光光度计法测定大鼠血浆中NO含量;用原位杂交方法观察神经元型一氧化氮合酶(neuronal nitric oxide synthase,nNOS)mRNA表达情况;用免疫组化方法观察nNOS蛋白表达情况.结果:FS+baclofen组NO含量低于FS组[(19.02±9.31)μmol/L比(40.03±9.12)μmol/L],同时nNOS蛋白和mRNA表达也较FS组减弱;而FS+phaclofen组NO含量高于FS组[(66.46±8.15)μmol/L比(40.03±9.12)μmol/L],同时nNOS蛋白和mRNA表达也较FS组增强.结论:反复热性惊厥过程中,GABABR的改变可影响NO/NOS体系的表达.     

新型气体信号分子硫化氢对左向右分流大鼠一氧化氮/一氧化氮合酶体系的影响

目的探讨内源性硫化氢(H2S)对左向右分流大鼠一氧化氮(NO)/一氧化氮合酶(NOS)体系的影响。方法将雄性SD大鼠随机分为分流组,分流+炔丙基甘氨酸(PPG)组,假手术组和假手术组+PPG组,每组8只。分流组及分流+PPG组大鼠经腹主动脉-下腔静脉穿刺建立左向右分流动物模型。术后4周,测量大鼠平均肺动脉压(MPAP);测定血浆NO、肺组织H2S、NO含量及NOS活性;用Western印迹方法测定肺组织eNOS含量。结果分流术后4周,分流组与假手术组比较,大鼠MPAP无明显变化;分流组与假手术组比较血浆NO(23·2μmol/L±3·6μmol/Lvs17·9μmol/L±3·4μmol/L,P<0·05)、肺组织H2S(37·6μmol/mg±2·1μmol/mgvs14·4μmol/mg±1·8μmol/mg,P<0·05)、肺组织NO(38·5±6·5μmol/μgvs31·8±6·5μmol/μg,P<0·05)、肺组织NOS活性(15·1U/mg±2·4U/mgvs12·0U/mg±1·4U/mg,P<0·05)及肺组织eNOS含量(0·3±0·1vs0·2±0·1,P<0·05)均明显升高。分流+PPG组大鼠MPAP较分流组及假手术组分别升高了15·82%和20·55%(19·5mmHg±1·7mmHgvs16·4mmHg±1·7mmHg和19·5mmHg±1·7mmHgvs15·5mmHg±1·3mmHg,P<0·05),肺组织H2S含量降低(28·8μmol/mg±2·2μmol/mgvs37·6μmol/mg±2·1μmol/mg,P<0·05),而血浆NO(27·8μmol/L±4·8μmol/Lvs23·2μmol/L±3·6μmol/L,P<0·05)、肺组织NO(46·0μmol/μg±6·0μmol/μgvs38·5μmol/μg±6·5μmol/μg,P<0·05)、NOS活性(20·9U/mg±3·9U/mgvs15·1U/mg±2·4U/mg,P<0·05)及eNOS含量均明显升高(0·4±0·1vs0·3±0·1,P<0·05)。结论内源性H2S可能通过抑制NO/NOS体系调节左向右分流大鼠肺动脉压力。     

雌二醇对大鼠缺血再灌注心肌诱生型及内皮型一氧化氮合酶活性的影响

目的 研究1713-雌二醇（E2）对缺血再灌注心肌诱生型一氧化氮合酶（iNOS）及内皮型一氧化氮合酶（eNOS）活性的影响,并探讨其心肌保护作用机制。方法采用Langendorff离体鼠心脏灌注模型,将40只卵巢切除（OVX）大鼠随机均分为心肌缺血前对照组（C组）：离体鼠心脏预灌注15min;缺血再灌注组（I—R组）：灌注改良St．ThomasⅡ停搏液,完成心肌缺血再灌注全过程;溶剂对照组（D组）：停搏液中含0．1％的二甲基亚砜（DMSO）,余同I—R组;E：组（E组）：停搏液中含0．1％DMSO及5μmol／L的E2,余同I—R组。检测缺血再灌注前后心肌iNOS和eNOS活性变化,测定冠状动脉流出液中肌酸磷酸激酶（CPK）、乳酸脱氢酶（LDH）、一氧化氮（NO）的含量以及心脏功能的变化,观察E2对心肌缺血再灌注损伤（MIRI）的影响。结果心肌缺血再灌注后eNOS活性下降（P〈0．01）,iNOS活性升高[C组（8．9±3．7）nmol·min^-1·g^-1,I—R组（15．8±2．4）nmol·min^-1·g^-1,D组（17．6±3．2）nmol·min^-1·g^-1,P〈0．01],E组iNOS活性升高更明显[（25．85±5．21）nmol·min^-1·g^-1,P〈0．01],I—R组及D组NO生成减少（均P〈0．05）,E组NO增加[C组（31±5）μmol／L,E组（33±6）μmol／L,P〈0．01],E组CPK和LDH产生减少（均P〈0．05）,E组心脏功能恢复良好（P〈0．05）。结论E2通过提高诱生型一氧化氮合酶活性,促进一氧化氮的产生,减轻心肌缺血再灌注损伤,促进心脏功能恢复。     

Effects of nitric oxide and hydrogen sulfide on the relaxation of pulmonary arteries in rats

Background The balance between vasodilation and vasoconstriction plays a major role in maintaining vascular homeostasis. However, the underlying mechanisms are unclear. More and more evidence suggested that there was an interaction in the regulation of vasorelaxation between nitric oxide （NO） and hydrogen sulfide （H2S）. We explored the interaction between and effects of NO and H2S on the relaxation of pulmonary arteries in rats. Methods Seven male Sprague-Dawley rats were anaesthetized with chloral hydrate and the pulmonary arteries of each rat separated for the study of vascular activities. The vasorelaxing activities of pulmonary artery rings in response to different doses of a NO donor, sodium nitroprusside （SNP）, or a H2S donor, sodium hydrogensulfide （NariS）, were measured in vitro. When pulmonary artery rings were treated with a cystathionine-y-lyase inhibitor, DL-propargylglycine, in the presence of SNP or a nitric oxide synthase inhibitor, Nω-nitro-L-arginine methyl ester, in the presence of NariS, the changes in relaxing activities were analyzed. Results The relaxation of pulmonary artery rings was in a dose dependent manner in response to either SNP or NariS. The relaxation rates of pulmonary artery rings increased from （30.90±4.62） % to （60.50±8.08） % when the concentration of SNP increased from 1 pmol/L to 3 pmol/L and from （26.13±4.12） % to （53.09±14.01） % when the concentration of NariS increased from 25 pmol/L to 100 μmol/L. However, when appropriate inhibitor was added, the relaxation responses to SNP and NariS decreased. Conclusions The results suggested that similarly to NO, H2S acted as a vasorelaxant either independently of, or synergistically with NO in the regulation of vasorelaxation. The interaction between NO and H2S played an important role in regulating relaxing activities of pulmonary arteries.     

Serum nitric oxide metabolite levels and the effect of antipsychotic therapy in schizophrenia

BACKGROUND: Recently it was proposed that nitric oxide metabolites (NO) may have a role in the pathophysiology of schizophrenia and major depressive disorders. The present study was performed to assess changes in serum nitric oxide metabolite levels in schizophrenic patients compared with healthy controls. Our secondary aim was to further evaluate the impact of psychopharmacologic treatment on circulating NO levels not assessed previously. METHODS: Serum NO levels of patients with schizophrenia (n=20) before and after 6 weeks of treatment were compared with those of healthy controls (n=20). Severity of schizophrenia and response to treatment were assessed with positive and negative symptoms of schizophrenia. NO levels were estimated by Griess method in serum samples. RESULTS: In patients with schizophrenia, pre-treatment serum NO levels were higher than those of control subjects (39.15 +/- 18.24 vs. 25.40 +/- 5.83 micromol/L, p=0.036) and also of post-treatment values (34.41 +/- 16.35 vs. 25.40 +/- 5.83 micromol/L, p=0.049), respectively. However, no significant difference was found between serum NO levels in pre- and post-treatment values. CONCLUSIONS: Our findings of increased serum NO levels in schizophrenic patients confirmed the role of NO in the pathophysiology of schizophrenia. However, we found that antipsychotic drugs do not reveal significant effects on serum levels of NO in schizophrenia in a 6-week treatment regimen. Further studies with longer therapy periods may suggest some new clues for novel treatment strategies employing antioxidants and NOS inhibitors in schizophrenia.     

血浆不对称二甲基精氨酸水平与冠状动脉硬化关系的研究

目的研究不对称二甲基精氨酸（ADMA）水平是否与冠状动脉粥样硬化的病变范围和严重程度有关。方法110例行冠状动脉造影术的患者根据造影结果分为冠状动脉造影正常的对照组22例,轻度动脉硬化组21例,造影显示冠状动脉内膜不光滑,但无明显的狭窄或狭窄小于50％;单支病变组22例,造影显示1支主要的冠状动脉分支出现明显狭窄（≥50％）;双支病变组22例,两支主要的冠状动脉分支出现明显狭窄;多支病变组23例,两支以上主要的冠状动脉分支出现明显狭窄或伴有左主干病变。血浆ADMA水平的检测采用酶联免疫法。结果除轻度动脉硬化组ADMA水平（1．21μmol／L±0．36μmol／L,P=0．288）偏低外,单支病变组、双支病变组和多支病变组患者的ADMA水平均高于对照组（1．52μmol／L±0．61μmol／L,1．67μmol／L±0．80μmol／L和2．60μmol／L±0．62μmol／L vs 0．79μmol／L±0．54μmol／L,P〈0．01）。经过多元相关与Logstic等级回归分析,ADMA水平与冠状动脉病变程度密切相关。结论血浆ADMA水平升高可以预测冠状动脉粥样硬化的发生,ADMA可能是一种新的冠心病危险因子。     

Anti-apoptotic effect of morphine-induced delayed preconditioning on pulmonary artery endothelial cells with anoxia/reoxygenation injury

Background Opioid preconditioning （PC） reduces anoxia/reoxygenation （A/R） injury to various cells. However, it remains unclear whether opioid-induced delayed PC would show anti-apoptotic effects on pulmonary artery endothelial cells （PAECs） suffering from A/R injury. The present study was conducted to elucidate this issue and to investigate the potential mechanism of opioid-induced delayed PC.
Methods Cultured porcine PAECs underwent 16-hour anoxia followed by 1-hour reoxygenation 24 hours after pretreatment with saline （NaCI; 0.9%） or morphine （1 μmol/L）. To determine the underlying mechanism, a non-selective KATe channel inhibitor glibenclamide （Glib; 10 μmol/L）, a nitric oxide （NO） synthase blocker NG-nitro-L-arginine methyl ester （L-NAME; 100 μmol/L）, and an opioid receptor antagonist naloxone （Nal; 10μmol/L） were given 30 minutes before the A/R load. The percentage of apoptotic cells was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） staining, eNOS mRNA level was measured by real-time polymerase chain reaction （PCR）. NO content of PAECs supernatants was measured with the Griess reagent.
Results Compared to the A/R PAECs, morphine-induced delayed PC significantly reduced PAECs apoptosis （（18.1±1.9）% vs （5.5±0.3）%; P 〈0.05）, increased NO release （（11.4±1.3） μmol/L vs （20.5±2.1） μmol/L, P 〈0.05）, and up-regulated eNOS gene expression nearly 9 times （P 〈0.05）. The anti-apoptosis effect of morphine was abolished by pretreatment with Glib, L-NAME and Nal, but the three agent-selves did not aggravate the A/R injury. Furthermore, L-NAME and Nal offset the enhanced release of NO caused by pretreatment with morphine.
Conclusions Morphine-induced delayed PC prevents A/R injury of PAECs. This effect may be mediated by activation of KATe channel via opioid receptor and NO signaling pathways.     

L-精氨酸干预低氧性肺血管结构重构机制的研究

探讨Ｌ－精氨酸干预低氧性肺血管结构重构的机制。方法将１８只Ｗｉｓｔａｒ大鼠采用区组随机法分为对照组、低氧组和低氧＋Ｌ－Ａｒｇ组。以右心导管法测定肺动脉压力,并对大示本进行显微结构观测和超微结构观察,同时分光光度法间接测定血浆一氧化氮（ＮＯ）含量,并对肺组织以内皮素－１（ＥＴ－１）ｃＲＮＡ探针进行原位杂交,研究肺动脉内皮细胞ＥＴ－１ｍＲＮＡ的表达。结果低氧组大鼠肺动脉平均压（ｍＰＡＰ）为２．７１ＫＰ     

Effect of continuous positive airway pressure treatment on vascular endothelial function in patients with obstructive sleep apnea hypopnea syndrome and coronary artery disease

Background Continuous positive airway pressure (CPAP) treatment has been proven to be effective in improving the symptoms of coexisting coronary heart disease (CHD) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). However, it is still unclear whether such improvements are linked to changes in vascular endothelial function. This research was carried out to investigate the effects of CPAP treatment on vascular endothelial function in patients with OSAHS and CHD.Methods Thirty-six patients with moderate or severe OSAHS and CHD undergoing three months of CPAP treatment were recruited for this study. The changes in their morning plasma nitric oxide (NO) and endothelin (ET) levels, NO/ET ratio, total ischemic burden (TIB) of the myocardium, apnea hypopnea index (AHI), and minimal and mean pulse oxygen saturation (SpO2) were compared and analyzed before and during CPAP treatment. Results Compared with the plasma levels of ET ［(51.39±11.69) ng/L］ and NO ［(36.67±11.86) μmol/L］, NO/ET (0.71±0.14), AHI (32.4±7.9), minimal SpO2 ［(68.9±11.4)%］, and myocardial TIB ［(66.29±16.37) mm·min］ before treatment, there were significant decreases in ET ［(33.41±10.03) ng/L］ （P&lt;0.05）, increases in NO ［(59.89±10.26) μmol/L］ and NO/ET (1.79±0.38) （P&lt;0.01）, decreases in AHI (1.9±0.5), and increases in minimal SpO2 ［(90.6±1.8) %］ （all P&lt;0.01） and myocardial TIB ［(36.42±10.87) mm·min］ （P&lt;0.05） after three months of CPAP treatment.Conclusion CPAP treatment may play an important role in the improvement and protection of vascular endothelial dysfunction and myocardial ischemia in OSAHS patients with CHD.