六月青多糖体外抗氧化作用的研究

目的：探讨六月青多糖（LYQP）体外清除自由基以及抗氧化的作用。方法：硫代巴比妥酸法测小鼠肝中丙二醛（MDA）含量，分光光度法测小鼠红细胞溶血和肝线粒体肿胀度，邻苯三酚自氧化法和邻二氮菲-Fe^2＋／H2O2体系研究LYQP对自由基的作用。结果：LYQP能有效抑制MDA的产生，减少小鼠红细胞溶血，减轻肝线粒体肿胀度，能抑制·OH的生成，但对O2^-的生成起促进作用。结论：LYQP有明显的体外抗氧化作用。     

蒲公英多糖降糖药理作用研究

目的:研究蒲公英多糖的降糖药理作用。方法:用DPPH和FRAP法对蒲公英多糖进行体外抗氧化研究,用微量法进行体外α-葡萄糖苷酶抑制实验;用四氧嘧啶复制小鼠糖尿病模型,灌胃给药14d后测定小鼠空腹血糖值,并分离肝组织测定超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-Px)等抗氧化指标。结果:DPPH和FRAP法的TEAC值分别为564.98、1399.55μmolTE.g-1),蒲公英多糖抑制α-葡萄糖苷酶活性(IC50=49.27μg·mL-1)。在体内,蒲公英多糖对正常小鼠的血糖值和抗氧化指标均无影响,但其可显著降低糖尿病模型小鼠的血糖且以高剂量的降糖作用最佳(P<0.01)。同时,蒲公英多糖可降低糖尿病模型小鼠的MDA含量,升高SOD和GSH-Px含量(P<0.01)。结论:蒲公英多糖具有很好的抗氧化活性、抑制α-葡萄糖苷酶活性及降血糖作用,提示其抗氧化作用可能是蒲公英多糖降血糖的机制之一。     

象拔蚌多糖体外抗氧化活性研究

目的研究象拔蚌多糖的体外抗氧化活性。方法检测象拔蚌多糖对1,1-二苯基-2-三硝基苯(DPPH)自由基清除活性及对大鼠肝脏匀浆一氧化氮合酶(NOS)、过氧化氢(H2O2)和丙二醛(MDA)含量的影响。结果象拔蚌多糖具有较强清除DPPH自由基活性,浓度达4 mg.mL-1时,抑制率为94.50%。象拔蚌多糖能降低大鼠肝脏匀浆H2O2和MDA含量,抑制NOS活性。结论象拔蚌多糖具有较强的体外抗氧化活性。     

泰山四叶参多糖体外抗氧化活性的研究

目的观察泰山四叶参多糖(PCL)体外抗氧化作用。方法羟自由基(.OH)由Fenton反应体系产生,超氧阴离子(O2-)由邻苯三酚自氧化法产生,硫代巴比妥酸法测定肝匀浆丙二醛(MDA)相对含量反映PCL对脂质过氧化的影响,并观察PCL对H2O2诱导红细胞溶血的影响。结果PCL能显著清除.OH,抑制小鼠肝匀浆脂质过氧化反应,EC50和IC50分别为230.2和479.0μg/mL,并能清除O2-和抑制H2O2诱导的氧化性溶血,EC50和IC50分别为1 048.5和1 674.2μg/mL。结论PCL有较强的体外抗氧化作用,其活性与剂量呈正相关。     

香菇多糖对H2O2损伤神经细胞保护作用的研究

目的研究香菇多糖(lentinan)对H2O2损伤体外原代培养大鼠皮层神经细胞的保护作用,并初步探讨其作用机制。方法体外培养胚胎大鼠大脑皮层神经细胞,建立H2O2氧化应激损伤模型,观察香菇多糖的保护作用。结果香菇多糖能显著提高氧化损伤神经细胞的生存率,降低培养液中乳酸脱氢酶(LDH)的漏出量和一氧化氮(NO)含量,抑制细胞内丙二醛(MDA)的生成,提高细胞内超氧歧化酶(SOD)的活性。结论香菇多糖对H2O2损伤神经细胞具有显著的保护作用,其机制可能与其抗氧化作用有关。     

硫酸酯化海洋真菌多糖制备及其体外抗氧化作用研究

对碱提海洋真菌(Keissleriella sp.YC4108)多糖YCC进行硫酸酯化产物制备并研究其体外抗氧化作用.利用碱提法从海洋真菌(YC4108)的发酵菌丝体中获得一种结构全新多糖YCC,通过氯磺酸-吡啶法对YCC进行硫酸酯化修饰,并体外观察硫酸酯化多糖对超氧化物自由基清除作用、羟基自由基清除作用、丙二醛(MDA)清除作用以及总抗氧化活性.结果:通过碱提得到一种重均相对分子质量为66 k的海洋真菌多糖YCC,硫酸酯化后得到3种不同取代度的硫酸酯化产物YCC-SL,YCC-SM和YCC-SH.YCC-SM和YCC-SH对超氧阴离子、羟自由基和MDA具有明显的清除作用,在总抗氧化能力实验中也表现出较强的活性.结论:随着硫酸基团含量的增加,抗氧化活性大大提高.     

楔形角叉菜的抗氧化及保护线粒体作用

目的观察楔形角叉菜水提液及多糖是否具有清除超氧阴离子(O2.-)、抗氧化、保护线粒体作用。方法以Fe2 -L-半胱氨酸(L-Cys)体系体外诱发鼠肝、脑线粒体及匀浆脂质过氧化并导致线粒体肿胀。以还原型辅酶I-吩嗪硫酸甲酯-氮蓝四唑(NADH-PMS-NBT)系统产生O2.—,用分光光度法测定脂质过氧化产物丙二醛(MDA)含量、线粒体肿胀度和O2.—的清除情况。结果楔形角叉菜水提液及多糖可明显抑制MDA生成及线粒体肿胀,并能明显清除O2.—,且呈剂量效应关系。结论楔形角叉菜水提液及多糖具有清除超氧阴离子、抗氧化及保护线粒体功能,多糖为楔形角叉菜抗氧化、保护线粒体的活性成分。     

石斛多糖抗氧化活性研究

目的研究石斛多糖的体内、体外抗氧化活性。方法①体外抗氧化实验：用化学反应法检测石斛多糖对邻苯三酚自氧化反应产生的超氧阴离子和Fenton反应产生的羟自由基的清除作用;②体内抗氧化实验：昆明种小鼠随机分为空白对照组、小剂量组、中剂量组和大剂量组,每组10只。研究石斛多糖对小鼠血清及肝组织中SOD、GSH-Px、MDA的影响。结果石斛多糖具有清除羟基自由基和超氧阴离子自由基的作用,可显著提高小鼠血清和肝组织中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）活力,降低丙二醛（MDA）含量。结论石斛多糖具有明显的抗氧化活性,为进一步开发石斛药材提供依据。     

新会陈皮多糖的体外抗氧化作用及总糖含量测定

目的研究新会陈皮多糖的体外抗氧化作用并测定其总糖含量。方法苯酚-硫酸比色法测定陈皮多糖的总糖含量;Fenton法、DPPH（1,1-Diphenyl-2-picrylhydrazyl）法和FRAP（Ferric Reducing Antioxidant Powder）法,以抗坏血酸为阳性对照、比色法测定,共同评价新会陈皮多糖的抗氧化作用。结果新会陈皮多糖在体外能明显清除羟自由基、DPPH自由基和还原Fe^3＋,并且体外抗氧化作用均随其浓度的增大而增大;总糖含量为7．20％。结论新会陈皮多糖具有明显的体外抗氧化作用。     

盐酸川芎嗪体外抗氧化作用的研究

目的探讨盐酸川芎嗪体外抗氧化作用。方法采用红细胞自氧化溶血、H2O2所致红细胞氧化溶血,肝匀浆MDA生成和Fe2+诱导的肝匀浆MDA生成,用比色法测定。结果盐酸川芎嗪体外给药能明显抑制家兔红细胞自氧化和H2O2所致红细胞溶血,并抑制肝匀浆自发性和Fe2+诱导的脂质过氧化反应。结论盐酸川芎嗪具有体外抗氧化作用,对红细胞和肝组织细胞具有膜保护作用。     

alpha-glucosidase (CHO) (Genzyme)

Genzyme General is developing recombinant human alpha-glucosidase, produced in mammalian cell culture, as a potential treatment for Pompe disease. By July 2004, enrollment was completed in two clinical trials and an observational study in adults. Genzyme was planning to file for regulatory approval in Europe during 2004, followed by filings in the US and Japan in mid-2005.     

(S)-oxybutynin (Sepracor)

Sepracor is developing (S)-oxybutynin, a single-isomer version of Alza's Ditropan (racemic oxybutynin), a muscarinic acetylcholine receptor antagonist, as a potential treatment for urinary incontinence.     

Allosteric interaction of zinc with recombinant alpha(1)beta(2)gamma(2) and alpha(1)beta(2) GABA(A) receptors

In a recent study we have provided evidence that inhibition of native GABA(A) receptors by zinc depends primarily on the allosteric modulation of receptor gating. Both the kinetics and the sensitivity of the GABA(A) receptor to zinc depend on subunit composition, especially on the presence of the gamma(2) subunit. To analyze the mechanism of action of zinc its effects have been tested on recombinant alpha(1)beta(2)gamma(2) and alpha(1)beta(2) receptors expressed in HEK 293 cells. The currents produced by ultrafast application of GABA have been measured to assess the impact of zinc ions on GABA(A) receptor gating with resolution corresponding to the time scale of synaptic currents. While, as expected, zinc markedly reduced the peak amplitude of alpha(1)beta(2)-mediated currents, its effect on kinetics was significantly different from that observed for alpha(1)beta(2)gamma(2). In particular, unlike alpha(1)beta(2)gamma(2), zinc did not affect the onset of alpha(1)beta(2)-mediated responses. Moreover, zinc increased the extent of desensitisation of alpha(1)beta(2)gamma(2) receptors and reduced desensitisation of alpha(1)beta(2) ones. Quantitative analysis suggests that zinc exerts an allosteric modulation on both alpha(1)beta(2)gamma(2) and alpha(1)beta(2) receptors. Zinc effects on alpha(1)beta(2)gamma(2) were qualitatively similar to those reported for native receptors.     

Di(isononyl) phthalate (DINP) and di(isodecyl) phthalate (DIDP) are not mutagenic

Recently there have been reports of liver and kidney tumors in rodents following long-term exposure to di(isononyl) phthalate (DINP). Mechanistic studies suggested that the liver tumors were a consequence of peroxisomal proliferation, whereas the kidney tumors (found only in male rats) were associated with induction of alpha(2u)-globulin. Because both peroxisomal proliferation and alpha(2u)-globulin are considered to be non-genotoxic carcinogenic processes, it seemed appropriate to investigate the genotoxic potential of DINP. Additional studies were also conducted on di(isodecyl) phthalate (DIDP), a structurally related substance that also induces peroxisomal proliferation, although it has not been tested in a carcinogenicity bioassay. The DINP was tested in Salmonella, in vitro cytogenetics and mouse micronucleus assays, whereas DIDP was evaluated in a mouse micronucleus test. All of these tests produced negative results, i.e. neither phthalate was mutagenic in any of the test systems. These data are consistent with results of other published and unpublished genotoxicity tests and provide support for the hypothesis that the liver and kidney tumors induced by DINP were the result of non-genotoxic processes.     

Developmental toxicity of di-(C(7)-C(9) alkyl) phthalate and di-(C(9)-C(11) alkyl) phthalate in the rat

Two phthalate esters, di-(C(7)-C(9) alkyl) phthalate (D79P) and di-(C(9)-C(11) alkyl) phthalate (D911P), have been assessed for their potential to cause developmental toxicity in the rat. Groups of 22 timed-mated Sprague-Dawley rats were administered 250, 500, or 1000 mg/kg D79P or D911P daily by oral gavage (5 ml/kg) between gestation days (GD) 1 and 19. Control animals received the vehicle (olive oil) alone. On GD20, the animals were sacrificed and the fetuses examined. Treatment resulted in no signs of maternal toxicity, as assessed by adjusted maternal bodyweight gain throughout gestation and clinical examinations, and no effects upon litter size, fetal survival or bodyweight. Pups of the high dose D79P and intermediate and high dose D911P groups showed increased incidences of supernumerary lumbar ribs. There was a significant increase in dilated renal pelves in pups of the low dose D79P and high dose D911P groups, but only for D911P was there a significant trend. Consequently, the no observed adverse effect level (NOAEL) for maternal toxicity for both D79P and D911P is 1000 mg/kg/day. The NOAEL values for developmental toxicity are 500 mg/kg/day D79P and 250 mg/kg/day D911P.     

4（R）—（6—氨基—9H—嘌呤—9—基）—2（R）—（羟甲基）四氢呋喃—3（R）—醇的合成

为寻找抗HIV化合物,我们以D－核糖为原料,经甲基化、硅烷基化、还原裂解反应制得重要中间体1－脱氧核糖（5）,再通过形成环状亚砜化合物,与NaN3发生反应后,经过还原、缩合、环合、氨化、脱保护基反应制得异脱氧腺嘌呤核苷（1）,各步反应收率均超过70％。其抗HIV活性测定尚在进行中。     

1,2-环己二胺柠檬酸铂(Ⅱ)及异柠檬酸铂(Ⅱ)的合成和抗癌活性

报道了1,2-环己二胺异柠檬酸铂(Ⅱ)及1,2-环己二胺柠檬酸铂(Ⅱ)的合成及鉴定方法。抗癌试验表明前者在40及80mg/kg 剂量下对小鼠 L1210、P388及S180均有明显的抑瘤作用,且有部分动物可治愈;后者对 L1210也有明显的抑瘤作用,但较前者为弱。     

Two-generation reproduction toxicity studies of di-(C(7)-C(9) alkyl) phthalate and di-(C(9)-C(11) alkyl) phthalate in the rat

Di-(C(7)-C(9) alkyl) phthalate (D79P) and di-(C(9)-C(11) alkyl) phthalate (D911P), based on high-normality linear oxo-alcohols, have been assessed for their impact upon reproductive performance in Sprague-Dawley rats. Rats were continuously exposed to either D79P or D911P at dietary levels of 0%, 0.1%, 0.5%, or 1.0% over two generations. Selected F(0) offspring (F(1) generation) were exposed to the same dietary concentration of D79P or D911P as the respective F(0) animals, and were mated to produce F(1) offspring. Both D79P and D911P markedly reduced body weight gain in F(0) and F(1) adult males at the highest dose, but females were affected to a lesser extent. There was no impairment of fertility, fecundity, or development in either generation, but body weights of offspring in the 1.0% D79P and 1.0% D911P groups were slightly and transiently reduced over the weaning period. Although decreases in the weight of several organs were accounted for by depressed body weight, ovary weights were reduced in both generations exposed to 1.0% D79P, and epididymidal weights were slightly reduced in adults of both generations exposed to 1.0% D911P. However, ovarian function-assessed by the oestrus cycle and mating behaviour-and epididymidal sperm concentration, motility, and morphology were unaffected by either substance. Treatment resulted in liver changes, particularly in males, characterised by increased liver weight in young animals, histopathologic changes and reduced organ weight in mature animals, and an increase in palmitoyl CoA oxidase activity. In conclusion, neither D79P nor D911P impaired reproductive function in rats when administered in the diet at levels that induce systemic toxicity, and the NOAEL for effects on reproduction in the rat is 0.5% for both D79P and D911P.     

4（R）—（6—氨基—9—嘌呤基）—2（R）—（羟甲基）四氢呋喃—3（R）—醇的合成

为寻找抗免疫缺陷病毒化合物,以D－核糖为原料,经甲基化、硅烷基化、还原裂解反应制得重要中间体1－脱氧核糖（5）,再通过形成环状亚砜化合物,与NaN3发生反应后,经过还原、缩合、环合、氨化、脱保护基反应制得异脱氧腺嘌呤核苷（1）,各步反应收率均超过70％。