低硒对大鼠因管一氧化氮合酶和微循环的影响

采用低硒饲料饲养大鼠造成体内贫硒。１４周时测定血浆中脂质过氧化物,前列环素和血栓素的水平以及部分血液流变学指标。实验第３９周,测定血管组织一氧化氮合枰活怀及一氧化氮水平。     

低硒对大鼠血管一氧化氮合酶和微循环的影响

采用低硒饲料饲养大鼠造成体内贫硒。１４周时测定血浆中脂质过氧化物（ＬＰＯ）、前列环素（ＰＧＩ２）和血栓素（ＴＸＡ２）的水平以及部分血液流变学指标。实验第３９周,测定血管组织一氧化氮合酶（ＮＯＳ）活性及一氧化氮（ＮＯ）水平。结果显示,低硒饲料组的血管ＮＯＳ活性、ＮＯ水平显著低于常规饲料的对照组;而在实验第１４周时,当低硒饲料组的血硒、血谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）活性显著下降、血浆ＬＰＯ水平明显上升的同时,其对应的血浆６－酮－ＰＧＦ１α水平也显著降低,但其ＴＸＢ２与对照组无显著差异。此外,随着大鼠体内的贫硒,其红细胞变形能力下降,但红细胞聚集指数和血沉方程Ｋ值提高。因此,硒不足可能会通过影响ＮＯＳ活性和ＰＧＩ２的合成以及红细胞特性而损害微循环功能。     

两种含锌化合物对慢性染铅大鼠海马NADPH-d阳性神经元影响的比较

为探讨硫酸锌(ZnSO4)和牛磺酸锌(TZC)拮抗铅对学习记忆的损害的不同，采用NADPH-黄递酶(NADPH-d)组化，观察了饮用含0.2g／L醋酸铅(PbAc)饮水和含不同剂量(5．0，15．0g／kg)ZnSO4、(5．9、17．7g／kg)TZC饲料喂养的大鼠海马一氧化氮合酶(NOS)活性的变化。结果表明，各补锌组均不同程度地缓解铅致NOS活力减低，铅 低TZC组、铅 高ZnSO4组和铅 低ZnSO4组大鼠海马神经元的NOS活性明显高于染铅组，其中铅 低TZC组的保护作用最显著，而铅 高TZC组的NOS活性明显低于对照组，而接近染铅组水平。结论是锌对抗铅的毒性作用与锌的化学结合形式、锌的剂量密切相关。     

一氧化氮合酶的结构及其催化机理

综述了一氧化氮合酶的结构、功能和催化路径, 讨论了诱导型一氧化氮合酶的结构和功能的关系以及加氧氧化的机理.     

低剂量铅接触对大鼠神经行为的影响

为研究低剂量铅接触对大鼠神经行为的影响，采用神经行为测试方法进行观察，再测定大鼠血铅及脑铅值。通过对照组与控制组进行比较，结果表明：低剂量铅接触能引起脑负及血铅值的变化，并在神经行为与对照组有显著差异。     

铅对大鼠海马谷氨酸递质体外摄取和释放的影响

为了探讨铅损害学习记忆功能的神经生物学机制，用海马突触小体和脑片分别观察了铅在体外对谷氨酸递质摄取和释放的影响。结果显示，3．1－50.0μmol／L铅使海马突触小体3H-DL-谷氨酸摄取量增加70．4％－193．2％，使脑片无钙状态下的自发性释放量增加23．2％－66．2％，并均有剂量-效应关系。但是在含钙介质中，当铅染毒剂量从1．0μmol/L增加为50．0μmol/L时，3H－DL-谷氨酸的自发性释放量减少22．6％－55．3％。而高钾去极化释放量增加89．3％－332．1％，而且也均存在剂量-效应关系。提示铅不仅能促进谷氨酸递质的灭活，而且还干扰它的释放过程。这可能会影响该递质的突触传递过程及其兴奋性作用，使LTP现象减弱或不能产生。     

褶合光谱法测定β-半乳糖苷酶的活性

运用褶合光谱法建立了 β 半乳糖苷酶的最佳褶合光谱以及该酶在最佳测试条件下的线性方程 :Qj=1.90 6× 10 -2 +4 .946× 10 -3 C +1.90 9× 10 -4 C2 ,r =1.0 0 0 0 ;对已瞬时转染 β 半乳糖苷酶表达载体的COS 1细胞提取液样品中的 β 半乳糖苷酶的活性进行了测定 ,并与吸光度值分析法相对照。结果表明 :本法快速、简便、准确 ,在生化分析中有广泛的应用价值     

雄黄对大鼠脑组织能量代谢的影响

将32只Wistar大鼠随机分为对照组(口服0.5%羧甲基纤维素钠溶液)以及低剂量(0.3g/kg)、中剂量(0.9g/kg)和高剂量(2.7g/kg)雄黄混悬液处理组,通过6周连续灌胃给服雄黄混悬液,采用高效液相色谱法测定大鼠脑组织中三磷酸腺甙(ATP)的含量,研究了雄黄对大鼠脑组织能量代谢的影响.结果表明,与对照组比较,雄黄染毒组大鼠脑组织中ATP含量均呈下降趋势(P<0.05),不同剂量组间未表现明显差异(P>0.05).这表明雄黄对大鼠脑组织能量代谢具有一定的抑制作用.     

镧离子对植物体内过氧化物酶活性的影响

本文首次比较了在植物体内La³⁺与过氧化物酶(POD)的相互作用和在植物体外La³⁺与辣根过氧化物酶(HRP)的相互作用。在植物体内的研究表明,La³⁺能够明显改变POD的活性,并呈现低促高抑的“Hormesis效应”。用圆二色谱(CD)、紫外-可见(UV-Vis)吸收光谱和傅立叶变换红外(FTIR)光谱研究在植物体外La³⁺与HRP相互作用的结果表明,在模拟生理条件的溶液中,La³⁺对HRP的活性同样呈现低促高抑的＂Hormesis 效应＂。其作用机理可能是La³⁺通过与HRP中酰胺基的O或N键合,导致HRP二级结构变化,进而改变活性中心血红素中铁卟啉的化学结构,最终改变HRP的催化活性。     

Effects of Siqi Decoction on Concentration of Nitric Oxide and Activity of Nitric Oxide Synthase in Blood Serum of Rats with Myocardial Ischemia

To study the effects of Siqi decoction on rats with Myocardial Ischemia, the model of Myocardium Ischemia was made for the Wistar rats cured with posterior pituitary injection through vein in tail. Siqi decoction, Diaoxinxuekang（DK） and Fufangdanshenpian（FD）, the latter two drugs of which were effective TCM drugs of anti-Myocardial Ischemia at present, were administrated to the rats with Myocardium Ischemia for 5 days to compare the effect of anti-Myocardium Ischemia as reference drugs by measuring the changes of NO concentration and activity of NOS in the rat blood serum with Myocardial Ischemia. There was a remarkable increase in the NO concentration and activity of NOS in serum in Siqi decoction groups compared with those in control group（p〈0.05）. The results of the prevention group in experiment of Siqi decoction are better than those of the cure group. Siqi decoction was really fit for Myocardium Ischemia via increasing NO concentration by stimulating the activity of NOS in serum. The effect of Siqi decoction against Myocardium Ischemia in preventive group is better than the curative that of Siqi decoction in the curative group.     

A General Procedure for Synthesis of NG-Alkyl,and NG-Aryl-L-Arginines as Potential Nitric Oxide Synthase inhibitors

A general procedure for the synthesis of N^G-alkyl, and N^G-aryl-L -arginines with relatively high overall yield is reported. The key step involved the coupling of protected L -ornithine 4 with isothiourea 7 to give the fully protected N^G-aryl-L -arginine derivative 8 . Subsequent deprotection of 8 in acidic condition provided the final target compound 9 with an overall yield of more than 80%.     

Calreticulin Transacetylase Mediates the Acetylation of Nitric Oxide Synthase by Polyphenolic Acetate

Our earlier investigations identified acetoxy drug: protein transacetylase (TAase), a unique enzyme in the endoplasmic reticulum (ER) catalyzing the transfer of acetyl groups from polyphenolic acetates (PA) to certain functional proteins. Recently we have established the identity of TAase with ER protein calreticulin (CR) and subsequently transacetylase function of CR was termed calreticulin transacetylase (CRTAase). CRTAase was purified and characterized from human placenta. CRTAase catalyzed the acetylation of a receptor protein nNOS, by a model PA 7, 8-diacetoxy-4-methylcoumarin (DAMC), which was visually confirmed by using antiacetyl lysine. The aim of this report was to provide tacit proof by providing mass spectrometry evidence for CRTAase catalyzed acetylation of purified nNOS by DAMC. For this purpose, purified nNOS was incubated with DAMC and CRTAase, the modified nNOS was analyzed by nanoscale LC-MS/MS, which recorded 11 distinct peptides with a significant score as acetylated on lysine residues. The distribution was in order: lysines-24, -33, -38, -131, and -229 of the PDZ domain, Lys-245 of the oxygenase domain, Lys-754 and -856 of FMN binding domain, Lys-989 of connecting domain and Lys-1300, -1321, and -1371 of the NADPH-binding domain were acetylated. The results documented in this paper highlighted for the first time modification of nNOS by way of acetylation. Our earlier work recorded the profound activation of platelet NADPH cytochrome P-450 reductase and the acetylation of the reductase protein by DAMC, which also remarkably enhanced intracellular levels of nitric oxide. The results reported here coupled with the aforementioned previous observations strongly implicate the possible role of the acetylation of the reductase domain of nitric oxide synthase (NOS) in the NOS activation. In addition, the acetylation of nNOS can be expected to potentiate the interaction with CR, eventually leading to the augmented catalytic activity of NOS and expression of the related biological effects.     

甲氨蝶呤与一氧化氮供体或一氧化氮合酶抑制剂组合物的合成

一氧化氮(nitric oxide,NO)在肿瘤病理生理过程中产生多方面的生化作用,诸如引起的某些核苷酸碱基的羟基化,参与免疫系统清除肿瘤细胞,促进肿瘤细胞凋亡和调节血管生成等．在此基础上,首次提出将NO供体(NO donor)或一氧化氮合酶(nitric oxide synthase,NOS)抑制剂分别连接到甲氨蝶呤(methotrexate,MTX,MTX本身就是NOS抑制剂)的α或γ位羧基上的设想,设计并合成出：(1)MTX-NO供体(3-羟甲基-4-苯基-1,2,5-噁二唑-2-氧化物,属于Furoxan衍生物,缩写为FU)：1a(MTX-α-FU),2a(MTX-γ-FU);(2)MTX-NOS抑制剂(L-N^ω-硝基精氨酸或L-N^ω-硝基精氨酸甲酯)：1b(MTX-α-L-N^ω-NO2-Arg),2b(MTX-γ-L-N^ω-NO2-Arg),1c(MTX-α-L-N^ω-NO2-Arg-OMe),2c(MTX-γ-L-N^ω-NO2-Arg-OMe)．在生物活性测试中,我们选择耐MTX细胞株K-562(慢性粒细胞性白血病急性病变细胞株),进行抗肿瘤活性测试,得到以下结果：(1)脂溶性差的MTX衍生物1b,2b抗肿瘤活性低于MTX,其它1a,2a;1c,2c均优于MTX;(2)连接有NO供体的MTX明显增强了MTX衍生物的抗肿瘤活性;(3)MTX中谷氨酸γ位组合物抗肿瘤活性均高于相应的α位异构体的活性．以上初步结果,将对进一步研究NO抗肿瘤作用以及新的抗肿瘤药物设计提供新的思路,对肿瘤临床化疗也有一定的参考价值．     

密陀僧中氧化铅及微量元素的含量测定

分别采用EDTA滴定法和等离子体发射光谱法测定了密陀僧中主成分氧化铅和18种微量元素的含量，本文可作为临床用药的参考。     

Fluorescent Nitric Oxide Photodonors Based on BODIPY and Rhodamine Antennae

Two novel NO photodonors (NOPDs) based on BODIPY and Rhodamine antennae activatable with the highly biocompatible green light are reported. Both NOPDs exhibit considerable fluorescence emission and release NO with remarkable quantum efficiencies. The combination of the photoreleasing and emissive performance for both compounds is superior to those exhibited by other NOPDs based on similar light-harvesting centres, making them very intriguing for image-guided phototherapeutic applications. Preliminary biological data prove their easy visualization in cell environment due to the intense green and orange-red fluorescence and their photodynamic action on cancer cells due to the NO photo-liberated.     

Nickel Hexacyanoferrate‐Based Sensor Electrode for the Detection of Nitric Oxide at Low Potentials

Recently transition metal hexacyanoferrates, analogues of Prussian Blue, have found application in electroanalysis for the detection of biologically relevant species. Our study describes the development of a novel electrode based on nickel hexacyanoferrate (NiHCF) for the sensorial NO determination. A NiHCF layer was deposited on platinum by cyclic voltammetry in a solution of nickel (II) chloride and potassium hexacyanoferrate (III). The electrode was found to be active for NO reduction. The interaction with the radical was studied voltammetrically within the range from 0 V up to +0.4 V vs. Ag/AgCl/1 M KCl. The most appropriate potential for an amperometric detection was determined to be +0.25 V due to the advantageous signal/noise ratio. The sensitivity of the electrodes was found to be 2.0–2.3 A M^?1 cm^?2. The sensor response of the most important interferents for NO analysis, hydrogen peroxide, ascorbic acid and nitrite, was measured and determined to be sufficiently low.     

汽油铅与血铅的关系

论述了汽油铅对人体血铅水平的影响，主要内容包括：血铅水平与大气铅水平的关系，大气铅水平与加铅汽油耗量的关系，汽油铅耗量与居民血铅水平的关系。