一氧化碳对血脂,脂质过氧化物含量及动脉粥样硬化影响的研究

健康雄性SD大鼠吸入62.6、375、750mg/m~3 CO,中、高浓度CO使大鼠血COHb、血清TG、LDL-CH及LPO含量增高,750mg/m~3 CO使主动脉内膜出现内皮下水肿、内皮细胞间裂隙及细胞核扭曲、变形等超微结构改变。提示:脂质过氧化、脂质代谢及主动脉内膜超微结构的改变,是CO所致动脉粥样硬化的重要病因学因素。     

绿原酸对肝纤维化大鼠脂质过氧化作用的影响

目的 研究绿原酸（CGA）对肝纤维化大鼠脂质过氧化作用的影响.方法 采用皮下注射CCl4诱导大鼠肝纤维化,以绿原酸（100 mg/kg）同时灌服给药8周,检测对照组、模型组和绿原酸组大鼠血清、肝组织中丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性,病理检测肝纤维化进展.结果 绿原酸能显著降低肝纤维化大鼠血清、肝组织中MDA含量,提高SOD的活性,抑制肝纤维化形成.结论 绿原酸具有很明显的保护肝细胞、抗肝纤维化的作用,其机制可能与抗脂质过氧化有关.     

Protective Effects of Salicylic Acid and Vitamin C on Sulfur Dioxide-Induced Lipid Peroxidation in Mice

The antioxidant effects of exogenous salicylic acid (SA) and vitamin C (Vit C) on the oxidative stress induced by 56 mg/m³ of sulfur dioxide (SO₂) in mouse livers and brains were investigated. The exposure of SO₂ caused significant elevation of thiobarbituric acid-reactive substance (TBARS) levels and reduction of enzyme activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in brain and liver, accompanied by a decrease in relative growth rate, when compared with controls. Application of moderate concentrations of SA and Vit C markedly reduced the SO₂-induced elevation of TBARS levels, with 5.5 mg/kg SA or 200 mg/kg Vit C being most effective. In contrast to the decrease of TBARS levels, the levels of SOD, POD, and CAT in liver and brain were significantly increased in comparison with controls. The polyacrylamide gel electrophoresis (PAGE) of total liver proteins showed that the SO₂ inhalation caused a 30-kD protein band disappearance compared with the control. However, the band remained unchanged in the samples treated with 5.5 and 8.25 mg/kg SA or 100, 200, and 400 mg/kg Vit C. Therefore, this protein band may serve as a marker for the damage induced by SO₂ and an additional basis for drug screening and selection.     

Enhancement of Platelet Aggregation by Ursolic Acid and Oleanolic Acid

The pentacyclic triterpenoid ursolic acid (UA) and its isomer oleanolic acid (OA) are ubiquitous in food and plant medicine, and thus are easily exposed to the population through natural contact or intentional use. Although they have diverse health benefits, reported cardiovascular protective activity is contentious. In this study, the effect of UA and OA on platelet aggregation was examined on the basis that alteration of platelet activity is a potential process contributing to cardiovascular events. Treatment of UA enhanced platelet aggregation induced by thrombin or ADP, which was concentration-dependent in a range of 5–50 μM. Quite comparable results were obtained with OA, in which OA-treated platelets also exhibited an exaggerated response to either thrombin or ADP. UA treatment potentiated aggregation of whole blood, while OA failed to increase aggregation by thrombin. UA and OA did not affect plasma coagulation assessed by measuring prothrombin time and activated partial thromboplastin time. These results indicate that both UA and OA are capable of making platelets susceptible to aggregatory stimuli, and platelets rather than clotting factors are the primary target of them in proaggregatory activity. These compounds need to be used with caution, especially in the population with a predisposition to cardiovascular events.     

抗坏血酸氯化钠注射液的制备及质量控制

目的:制备100mL装量抗坏血酸氯化钠注射液并建立其质量控制方法。方法:以抗坏血酸为主药制备注射液;采用紫外-可见分光光度法测定其中主药的含量。结果:所制制剂检查、鉴别等均符合2005年版《中国药典》相关规定;抗坏血酸检测浓度的线性范围为4.0～12.0μg·mL-1(r=0.9999);平均回收率为99.85%(RSD=0.75%,n=6)。结论:本制剂组方合理,制备工艺简单可行,质量稳定可控。     

Scavenging of Free-radicals and Inhibition of Lipid Peroxidation by 3-Phenylsydnone

The antioxidant properties of 3-phenylsydnone were studied in various models in-vitro. 3-Phenylsydnone scavenged the stable free radical, 1,1-diphenyl-2-picrylhydrazyl, and inhibited the degradation of deoxyribose mediated by hydroxyl radicals, although, to a lesser extent than trolox, a water soluble analogue of vitamin E. Many antioxidants possess pro-oxidant properties due to their ability to reduce ferric ions; however, 3-phenylsydnone was free from pro-oxidant properties, and also inhibited the lipid peroxidation induced by iron, in rat brain homogenates.     

Exogenous GTP Increases Cyclic GMP and Inhibits Thrombin-Induced Aggregation of Washed Human Platelets: Comparison with ATP,Adenosine and Guanosine

Abstract: The effects of exogenous guanosine 5′-triphosphate (GTP), guanosine, adenosine 5′-triphosphate (ATP) and adenosine on platelet aggregation, serotonin secretion and cyclic nucleotide accumulation were studied using thrombin-stimulated washed human platelets. GTP (10 μM-1 mM) dose-dependently inhibited thrombin-induced aggregation and serotonin secretion. The inhibition of aggregation was accompanied by an increase in platelet cyclic GMP. GTP did not affect cyclic AMP concentration. Adenosine (1 μM-1 mM) dose-dependently inhibited thrombin-induced aggregation and serotonin secretion, and increased cyclic AMP. ATP at high concentrations (100 μM-1 mM) inhibited aggregation and serotonin secretion, and 1 mM ATP increased cyclic AMP. Guanosine was relatively ineffective in preventing aggregation and serotonin secretion and did not affect cyclic GMP. The rank order of inhibition of thrombin-induced aggregation of washed human platelets was adenosine > GTP > ATP > guanosine. In conclusion, exogenous GTP inhibits thrombin-induced aggregation and serotonin secretion of washed human platelets by increasing cyclic GMP. The results raise the possibility of a cell membrane site of action for GTP in platelets which mediates the activation of soluble guanylate cyclase suggesting that GTP may have a local antithrombotic effect also in vivo.     

心肌肽素对大鼠心肌匀浆脂质过氧化的影响

目的 观察小分子多肽类物质心肌肽素对心肌匀浆孵育脂质过氧化的影响。方法 制备５％（质量体积浓度）大鼠新鲜心肌匀浆液。取１．９ｍｌ均浆液,分别加入０．１ｍｌ生理盐水及不同浓度心肌肽素,使心肌肽素终浓度分别为５,１０,２０μｇ／ｍｌ,置３７℃水浴振荡６０ｍｉｎ。分别以硫代巴比妥酸法和光化学扩增法检测心肌脂质过氧化反应终产物ＭＤＡ的含量及细胞内ＳＯＤ活性。结果 心肌肽素可剂量依赖性地显著降低心肌匀浆中Ｍ     

氯化镍对小鼠睾丸影响的研究

氯化镍可引起小鼠精子数减少、活动能降低及畸形率增高。电镜下看到支持细胞受损严重,精原细胞、精母细胞、精细胞及精子亦均受到不同程度的损害。     

胃粘膜分泌维生素C的初步研究

为了研究胃粘膜分泌维生素Ｃ的情况，对１０例胃粘膜正常的人进行了研究。所有被研究者在禁食标饮１０小时后，先观察空腹基础状态下胃液中维生素Ｃ浓度及胃粘膜的维生素Ｃ分泌，然后静脉注射维生素Ｃ，再观察给药后不同时间胃液中维生素Ｃ浓度的变化。结果空腹基础状态下胃液中维生素Ｃ浓度明显高于血中维生素Ｃ浓度，静脉注射维生素Ｃ后，胃液中维生素Ｃ浓度逐渐增高，提示胃粘膜有分泌维生素Ｃ的能力。胃粘膜的维生素Ｃ分泌量平均     

虫草菌丝对肝纤维化小鼠肝脏脂质过氧化的影响

目的:明确虫草菌丝对四氯化碳小鼠肝纤维化的作用及肝脏脂质过氧化的影响.方法:四氯化(碳)皮下注射复制BALB/c小鼠肝纤维化模型,虫草组在造模同时予以虫草菌丝煎剂,直至造模结束.HE染色观察肝组织炎症天狼猩红染色观察肝脏胶原沉积,生化法测定肝组织羟脯氨酸(HyP)、超氧化物歧化酶(SOD)含量,Nothern Blot测定Ⅰ型前(人)原mRNA.结果:与正常小鼠比较,肝纤维化小鼠肝脏肝静脉与汇管区周围肝细胞明显脂肪变性,肝脏胶原沉积,可见纤维(I)隔形成,肝脏Hyp含量及Ⅰ型前胶原基因表达均显著增加,肝脏SOD减少;与模型组比较,虫草组肝脏炎症与胶原沉积减(少)(P＜0.01),Hyp含量及Ⅰ型前胶原mRNA表达明显降低(P＜0.01),SOD活性明显增加(P＜0.01).结论:虫草菌丝制(剂)良好的抗肝纤维化作用,其作用机制可能提高肝脏SOD水平、降低Ⅰ型前胶原mRNA的表达有关.     

同型半胱氨酸对大鼠主动脉内皮细胞脂质过氧化的影响

目的：探讨同型半胱氨酸（ＨＣＹ）对大鼠主动脉内皮细胞（ＥＣ）脂质过氧化的影响。方法：取体重１５０～２００ｇ健康雄性Ｗｉｓｔａｒ大鼠胸主动脉,以组织贴块法进行ＥＣ培养,第５代用于实验,各实验组及对照组均为６孔细胞,实验组加入５ｍｍｏｌ／ＬＨＣＹ或５ｍｍｏｌ／ＬＨＣＹ＋２５μｍｏｌ／ＬＣｕ＾２＋对照组不加ＨＣＹ。分别在不同时限观察细胞形态并测定丙二醛（ＭＤ）浓度,超氧化物歧化酶（ＳＯＤ）活性和乳酸脱氢     

Experimental Exposure to Wood-Smoke Particles in Healthy Humans: Effects on Markers of Inflammation,Coagulation, and Lipid Peroxidation

Particulate air pollution is known to increase cardiovascular morbidity and mortality. Proposed mechanisms underlying this increase include effects on inflammation, coagulation factors, and oxidative stress, which could increase the risk of coronary events and atherosclerosis. The aim of this study was to examine whether short-term exposure to wood smoke affects markers of inflammation, blood hemostasis, and lipid peroxidation in healthy humans. Thirteen subjects were exposed to wood smoke and clean air in a chamber during two 4-h sessions, 1 wk apart. The mass concentrations of fine particles at wood smoke exposure were 240–280 μg/m³, and number concentrations were 95,000–180,000/cm³. About half of the particles were ultrafine (< 100 nm). Blood and urine samples were taken before and after the experiment. Exposure to wood smoke increased the levels of serum amyloid A, a cardiovascular risk factor, as well as factor VIII in plasma and the factor VIII/von Willebrand factor ratio, indicating a slight effect on the balance of coagulation factors. Moreover, there was an increased urinary excretion of free 8-iso-prostaglandin_2α, a major F₂-isoprostane, though this was based on nine subjects only, indicating a temporary increase in free radical-mediated lipid peroxidation. Thus, wood-smoke particles at levels that can be found in smoky indoor environments seem to affect inflammation, coagulation, and possibly lipid peroxidation. These factors may be involved in the mechanisms whereby particulate air pollution affects cardiovascular morbidity and mortality. The exposure setup could be used to establish which particle characteristics are critical for the effects.     

Effects of Antioxidants on Oxygen Toxicity in Vivo and Lipid Peroxidation in Vitro

Abstract: Convulsions and pulmonary damage result when animals are exposed to hyperbaric oxygen at pressures above about 300 kPa. Several hydroxyl radical scavengers (namely dimethylsulphoxide, dimethylthiourea and mannitol), the iron chelator desferoxamine and the lipid antioxidant butylated hydroxytoluene were tested for possible protection against such hyperbaric oxygen toxicity. Dimethylthiourea and dimethylsulphoxide prolonged the latency to the first convulsion, but, surprisingly, dimethylthiourea very significantly increased pulmonary damage at both pressures used (515 and 585 kPa). Desferoxamine also slightly increased lung damage at 585 kPa. Other antioxidants did not alter neurotoxicity or pulmonary toxicity induced by hyperbaric oxygen at 515 or 585 kPa. The antioxidants were also tested for their ability to inhibit lipid peroxidation (TBARS formation) in vitro. Desferoxamine (5 and 50 μM), and butylated hydroxytoluene (0.1 mM and 1 mM) greatly inhibited TBARS formation in brain and lung homogenates incubated at 37°. None of the hydroxyl radical scavengers affected TBARS levels in homogenates. There was no correlation between in vitro inhibition of lipid peroxidation and in vivo protection against oxygen toxicity.     

Inhibitory Effects of Isoflavones in Sophora mooracrotiana on Lipid Peroxidation by Superoxide

The possible inhibitory effects were investigated for three isoflavones: sophoraisoflavone A, and licoisoflavones A and B, isolated from Sophora mooracrotiana Benth ex Baker, on lipid peroxidation by superoxide anion. They inhibited the production of lipid peroxidation each by superoxide anion and the generation of superoxide anion by the xanthinexanthine oxidase system. Their effects were similar to superoxide dismutase as a superoxide anion scavenger. These results demonstrate that these isoflavones have inhibitory effects on oxidative stress.     

UV-Dependent Quinolone-Induced Human Erythrocyte Membrane Lipid Peroxidation: Studies on the Phototoxicity of Y-26611, a New Quinolone Derivative

Quinolone antibacterial drugs are widely used as oral therapeutic agents. However, in some patients they cause ultraviolet (UV)-dependent dermatitis. Using lipid peroxidation as an index of phototoxicity, we studied the effects of a new quinolone derivative, Y-26611 together with ofloxacin, sparofloxicin and lomefloxacin on washed human erythrocyte suspensions. Irradiation of erythrocytes with UV-A or UV-B for 60 min. in the presence of Y-26611 (30-600 μg/ml) strong dose dependent lipid peroxidation, up to 17.01 nmoles/ml was induced. Under identical conditions, lipid peroxidation induced by up to 600 μg/ml ofloxacin, sparofloxacin or lomefloxacin were 0.94, 3.36 and 2.98 nmoles/ml respectively. The lipid peroxidation was entirely dependent on both UV as well as the drug. The lipid peroxidation responses to drug + UV could completely be inhibited by sodium azide (hydroxyl radical, HO- and singlet oxygen, ¹O₂ scavenger) or by phenyl N-tert-butylnitrone (PBN, HO and superoxide anion radical, O₂^? scavenger). It is likely that reactive oxygen species generated by interaction between UV-sensitized drug molecules and oxygen molecules mediate erythrocyte membrane lipid peroxidation. The method used in this study is rapid and convenient for screening drugs for UV-dependent cytoloxicity.     

葛根素对人红细胞变形性和聚集性的影响

目的:观察葛根素对人红细胞变形性和聚集性的影响.方法:将健康献血者血液用肝素抗凝(34 U/ml)用生理盐水(生理盐水组)和葛根素(葛根素组)将其稀释为不同浓度,用红细胞变形聚集仪分别测量生理盐水组和葛根素组的红细胞变形性和聚集性.结果:与生理盐水组对照,葛根素能有效地降低红细胞变形性(P＜0.01,P＜0.05),同时也降低红细胞聚集性(P＜0.01).结论:葛根素可以改善红细胞变形性和聚集性,为临床治疗糖尿病、冠心病提供了理论依据.     

5种中药注射液对脂质过氧化及活性氧自由基作用的影响

本文用比色法和化学发光分析法测定丹皮酚,柴胡,当归,天麻,夏天无注射液对大鼠肝均浆过氧化脂质影响及对Ｈ２Ｏ２－鲁米诺发光体系中Ｈ２Ｏ２的清除作用。     

Effects on Lipid Peroxidation and Antioxidative Enzymes of Euonymus alatus in Cultured Rat Hepatocytes

Abstract: The Euonymus alatus (Thunb.) Sieb. has long been used as a crude drug. In this paper, we investigate the effects of E. alatus on cultured hepatocyte cell system and lipid peroxidation in hydrogen peroxide (H₂O₂) treatment conditions. The study covers the physiological activity (the antioxidative activity and the nitrite‐scavenging effect) of E. alatus. H₂O₂ that can produce intracellular free radical was used for inducer of the peroxidation of cellular lipids. Treatment of E. alatus attenuated in cell killing enhanced by increasing concentrations of H₂O₂. The increased malondialdehyde level induced by H₂O₂ treatment was reduced by pre‐treatment of E. alatus. Furthermore, addition of E. alatus in cell culture medium significantly reduced cell killing and content of intracellular antioxidants. Changes in nitrite‐scavenging effect of E. alatus at various concentrations (5–25 mg/ml) and various pH levels (pH 1.2, 4.2 and 6.0) were also observed. The present study was also done to investigate the effects of E. alatus on cultured hepatocyte cell system, H₂O₂‐induced cytotoxicity and antioxidative enzyme activities, including catalase, superoxide dismutase, glutathione peroxidase and glutathione S‐transferase in H₂O₂ treatment conditions. E. alatus treatment had significant protective or elevating activities on these antioxidative enzyme activities compared to a normal group. The results indicate that E. alatus provides a strong antioxidant protection of cells against H₂O₂‐induced oxidative stress.     

Biopharmaceutics: Biochemical Pharmacology: Inhibition of Human Platelet Aggregation by Diazeniumdiolates: Extent of Inhibition Correlates with Nitric Oxide Load Delivered

The profile of nitric oxide (NO) release from the diazeniumdiolate class of NO donors was evaluated using inhibition of platelet aggregation as a model. At 37°C, the NO complexes (Z)-1-{N-methyl-N-[6-(N-methylammoniohexyl)amino]}-diazen-1-ium-1, 2-diolate (dimethylhexanediamine complex), sodium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (diethylamine complex), (Z)-1-{N-3-aminopropyl-N-[N-(3-aminopropylammonio)butyl]amino}diazen-1-ium-1,2-diolate (spermine complex), and (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,22-diolate (diethylene-triamine complex) have half-lives of 1, 2 and 39min, and 20 h, respectively. All the diazeniumdiolates caused concentration-dependent inhibition of platelet aggregation; IC50 values (values for which the effect was half the maximum) were 26.0 ± 24.1, 34.9 ± 24.0 and 14.9 ± 6.4 nM for dimethylhexanediamine complex, diethylamine complex and spermine complex, respectively, when pre-incubated with platelets for one half-life. Inhibition by all compounds was time-dependent. Pretreatment of platelets with spermine complex for 5 and 39 min resulted in IC50 values of 1.7 ± 0.85 μM and 19.7 ± 0.12 nM, whereas IC50 values for sodium nitroprusside were 27.3 ± 1.25 nM and 25 nM (average, n = 2), at 5 and 39 min, respectively. Pre-incubation of each diazeniumdiolate at a concentration of 100 nM for 5 min at 37°C, which resulted in the theoretical delivery of NO loads from 96.9% down to 0.3%, resulted in decreasingly efficacious inhibition of platelet aggregation. Linear regression analysis of the theoretical NO load delivered against the actual maximum inhibition (%) showed a strong correlation (r² = 0.975). All four diazeniumdiolates caused concentration- and time-dependent inhibition of agonist-stimulated elevation of intra-platelet Ca²⁺ levels; IC50 values were, respectively, 8.7 ± 1.49nM and 11.5 ± 1.36nM for dimethylhexanediamine complex and diethylamine complex at their half-lives, and 176 ± 16.9 nM and > 100 μM, for spermine complex and diethylenetriamine complex at 2 min pre-incubation time. The respective nucleophiles not complexed with NO did not show anti-aggregatory properties or inhibition of agonist-induced elevation of intra-platelet Ca²⁺ levels. The inhibitory effects of all diazeniumdiolates tested were attenuated by 10 μm haemoglobin. These studies indicate that these compounds induce controlled, predictable release of NO at biological pH and temperature.