枸杞子糖缀合物及其糖链对LDL氧化修饰的抑制作用

目的　研究枸杞子糖缀合物及其糖链对LDL氧化修饰的抑制作用。方法　在Cu²⁺诱导的LDL氧化模型中测定了脂质过氧化产物硫代巴比妥酸反应物质（TBARS）的含量及LDL在琼脂糖凝胶电泳上的迁移率以反映从枸杞子中分离、纯化得到的糖缀合物及糖链对LDL氧化修饰的抑制作用。结果　枸杞子糖缀合物及糖链抗LDL氧化的能力是不同的,其中LbGp5可明显的抑制LDL的氧化。结论　枸杞子糖缀合物具有抗LDL氧化作用,而糖链不具有抗LDL氧化的作用。     

赤芍总苷对D-半乳糖衰老小鼠学习记忆及代谢产物的影响

目的　观察赤芍总苷对D 半乳糖所致衰老小鼠学习记忆及与神经介质调节相关酶及代谢产物的影响。方法　选用长期皮下注射D 半乳糖形成的衰老小鼠模型。结果　赤芍总苷对衰老小鼠的学习记忆障碍有显著的改善作用 ,穿梭试验中小鼠主动回避潜伏期和主动回避次数明显增加 ;水迷宫试验发现 ,赤芍总苷可有效提高小鼠的达岸正确率 ,减少小鼠的错误次数。赤芍总苷可显著降低衰老小鼠脑组织中单胺氧化酶 (MAO)水平 ,提高胆碱酯酶 (CHE)活性 ;并抑制脂质过氧化产物丙二醛 (MDA)含量的增加 ,提高脑组织超氧化物岐化酶 (SOD)水平。此外 ,赤芍总苷对衰老小鼠免疫功能低下及脑萎缩状态有显著的改善。结论　赤芍总苷具有抗衰老及促进学习记忆能力的作用     

巨噬细胞对低密度脂蛋白的修饰和PGE2抗AS作用的实验研究

目的研究巨噬细胞对低密度脂蛋白(LDL)的修饰和前列腺素E2(PGE2)对动脉粥样硬化形成的抑制作用。方法以巨噬细胞(Mp)作用LDL,并设PGE2(20mg/L)组,检测每组过氧化脂质含量,谷胱甘肽过氧化物酶活性,及形态计量学测定细胞变化和含脂量。结果细胞修饰组的脂质过氧化物含量高于给PGE2组,而谷胱甘肽过氧化物酶活性显著低于给药组。作用24小时的修饰组细胞面积明显增大,摄脂增加,均分别显著高于给药组和细胞对照组。结论提示Mp能够氧化修饰LDL并能摄取脂质,导致泡沫细胞形成。大剂量PGE2有抗LDL氧化修饰,抑制Mp细胞摄脂,和泡沫细胞形成,从而抑制动脉粥样硬化发生的作用。     

α-甲基-4-(3-氧-2H-1,2-苯并异硒唑-2-基)苯乙酸对Cu2+和Fe2+氧化修饰人低密度脂蛋白的抑制作用

为观察α-甲基-4-(3-氧-2H-1,2-苯并异硒唑-2-基)苯乙酸(MBBA) 对Cu²⁺及Fe²⁺氧化修饰低密度脂蛋白(LDL)的保护作用及其作用机理，采用分光光度法测定LDL中丙二醛(MDA)和共轭双烯(CD)的产生量. MBBA(0.2-2 μmol·L^-１)能以剂量依赖性抑制Cu²⁺及Fe²⁺诱导的MDA和CD生 成. 2 μmol·L^-１的MBBA对Cu²⁺诱导LDL产生MDA和CD的抑制率分别为89.7%和60.3%. 0.5 mmol·L^-1 GSH对LDL产生MDA无影响，但能显著增强MBBA对MDA 生成的抑制作用. 上述结果表明MBBA 对LDL氧化修饰的抑制作用可能依赖于其GSH-Px样活性的作用和(或)直接还原脂质氢过氧化物的作用.     

两种微藻油对高脂小鼠脂类代谢及脂质过氧化作用的影响

目的探讨两种海洋微藻油(小球藻油和等边金藻油)对饲喂高脂饲料小鼠血脂水平及脂质过氧化的影响。方法 100只小鼠分为5组,分别为对照组,高脂模型组,小球藻油组,等鞭金藻油组及鱼油组。饲喂高脂饲料及相应药物6W后,测血脂水平及肝脏和血清的丙二醛(MDA)水平及过氧化氢酶(CAT)、超氧化物歧化酶(SOD)活性。结果两种微藻油可使高脂小鼠血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)含量降低,而高密度脂蛋白胆固醇(HDL-C)升高。与模型组相比,两种微藻油处理组的血清和肝组织的SOD、CAT活性明显增强,脂质过氧化产物MDA含量下降。而两种微藻之间,以小球藻油具有较高的SOD和CAT活性。结论两种微藻油具有显著调血脂作用,并可增强体内抗氧化酶活性,降低因高脂饲料引起的小鼠脂质过氧化。     

卡托普利保护大鼠缺血再灌注心肌与抗心肌脂质过氧化的关系(英文)

本实验分别用大鼠在体、离体心脏和培养心肌细胞观察了卡托普利(甲巯丙脯酸)抗心肌缺血再灌注损伤与抗脂质过氧化作用。离体心脏缺氧缺糖45 min后再给氧30 min以及在体心脏缺血3 h后再灌注1h,心肌超氧化物歧化酶(SOD)活性明显下降而丙二醛(MDA)含量显著升高。卡托普利能显著保护再灌注(或再给氧)时心肌SOD活性和降低MDA含量。培养心肌细胞缺氧缺糖6 h,细胞MDA含量和乳酸脱氢酶(LDH)释放显著增加。卡托普利显著降低MDA含量和LDH释放。该作用能被吲哚美辛所取消。IIoprost显示有卡托普利相似的保护作用。结果表明卡托普利的保护作用与抗氧自由基和抗脂质过氧化有关。其机理主要通过促进心肌前列环素释放而发挥作用。     

金粉蕨素对脂质过氧化损伤内皮细胞的保护作用

目的 :探讨金粉蕨素对脂质过氧化损伤人内皮细胞株 (ECV30 4 )的保护作用及其可能的分子作用机制。方法 :在铜离子诱发的低密度脂蛋白氧化修饰的基础上 ,建立内皮细胞 (endothelialcell ,EC)的脂质过氧化损伤模型 ;采用MTT比色法、硝酸还原酶法等方法 ,测定不同浓度金粉蕨素 (1.0、5 .0、10 .0 μmol·L-1)对EC生长抑制率、硫代巴比妥反应物 (thiobarbituricacid reactivesubstances ,TBARS)、LDH及NO含量的影响。结果 :氧化修饰低密度脂蛋白 (oxidativelymodifiedlowdensitylipoprotein ,ox LDL)作用 2 4h后 ,对EC的生长增殖有明显的抑制作用 ,细胞培养液中TBARS、LDH水平显著升高 ,NO含量降价 ;而不同浓度金粉蕨素与oxLDL共同孵育2 4h ,呈剂量依赖性对抗oxLDL对EC的损伤 ,并促进EC增殖 ,同时使培养液中TBARS、LDH含量降低 ,NO含量回升。结论 :脂质过氧化能直接损伤内皮细胞 ,金粉蕨素对脂质过氧化损伤的内皮细胞有保护作用     

异丹叶大黄素在体外对Cu2+介导的人低密度脂蛋白过氧化的抑制作用

目的研究异丹叶大黄素(Iso)对Cu2 介导的人低密度脂蛋白(LDL)过氧化及氧化LDL(ox-LDL)对小鼠巨噬细胞毒性的抑制作用.方法用序贯超离心法分离血脂正常的供血者血清LDL,分离的LDL 1 mg·mL-1 磷酸缓冲液(pH 7.4), 与10 μmol·L-1 CuSO4于37℃水浴温育10 h 以引起LDL过氧化,给药组预先加入不同浓度Iso,对照组加等量生理盐水,测定丙二醛(MDA)的生成量、维生素E的耗竭以及LDL电泳迁移率.另外测定用ox-LDL处理小鼠腹腔巨噬细胞线粒体的膜电位、吞噬刚果红及释放NO的量.结果 1-100 μmol·L-1 Iso 剂量依赖性地抑制Cu2 引起的人LDL氧化时MDA的生成量、维生素E的耗竭及电泳迁移率的升高.10 μmol·L-1 Iso能防止0.1 mg·mL-1 ox-LDL与小鼠腹腔巨噬细胞温育4 h 后线粒体膜电位的损伤、吞噬刚果红功能以及NO释放量的降低.结论 Iso在体外对Cu2 介导的LDL过氧化以及ox-LDL对小鼠巨噬细胞的毒性有保护作用.     

阿魏酸钠部分减轻氢化泼尼松引起的小鼠肝脏毒性

氢化泼尼松(Pred)20mg·kg^-1可明显增高小鼠sGPT与sGST水平,增加肝匀浆MDA含量及肝微粒体与线粒体膜流动性。表明Pred致sGPT及sGST水平增高与肝脂质过氧化作用增强及膜流动性改变有关。经1g阿魏酸钠(SF)100mg·kg^-1使sGPT与sGST水平降低,肝脏MDA含量减少,但sGPT与MDA仍高于正常对照组水平。肝微粒体膜流动性恢复,线粒体膜流动性进一步增高。电镜观察亦见线粒体仍有损害,提示SF不能完全对抗Pred所致肝损害。     

丹酚酸-A体外对人血清低密度脂蛋白氧化修饰的抑制作用

目的研究丹酚酸-A(Sal-A)对人血清低密度脂蛋白(LDL)氧化修饰的抑制作用。方法用Cu²⁺体外诱导LDL过氧化,观察Sal-A对MDA,脂褐素和维生素E含量,氧化LDL电泳迁移率以及对LDL氧化过程中自由基的产生及Sal-A螯合Cu²⁺的作用。结果LDL经Cu²⁺诱导过氧化后,丙二醛和脂褐素的生成增加,维生素E含量下降,LDL电泳迁移速度加快,LDL氧化过程中自由基的生成增加。10^-6～10^-4 mol·L^-1 Sal-A可剂量依赖性地抑制上述改变,并且Sal-A能螯合Cu²⁺。结论丹酚酸-A可有效地抑制Cu²⁺诱导的人LDL氧化,该作用可能与其清除自由基及螯合铜离子的能力有关。     

Natural phenylpropanoids protect endothelial cells against oxidized LDL-induced cytotoxicity

There is increasing evidence that oxidized low-density lipoproteins (Ox-LDL) might be involved in the pathogenesis of atherosclerosis and it has been reported that polyphenols inhibit LDL peroxidation and atherosclerosis. Minimally oxidized LDL (mOx-LDL) induce cytotoxicity in cultured bovine aortic endothelial cells (BAEC). The goal of this study was to test the protective effect of five natural polyphenols isolated from the aerial parts of Marrubium vulgare L. against mOx-LDL-induced cytotoxicity in BAEC. Four phenylpropanoid glycosides (acteoside 1, forsythoside B 2, arenarioside 3, ballotetroside 4) and one non-glycosidic derivative (caffeoyl-l-malic acid 5) were tested. These compounds inhibited both copper (Cu 2+)- and 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced in vitro LDL oxidation and preserved the morphological aspects of BAEC during their incubation with mOx-LDL. Furthermore, they reduced the accumulation of aldehydes in the cultured medium during the incubation of BAEC with mOx-LDL and prevented cellular LDH leakage during this period. These data suggest that natural phenylpropanoids inhibit mOx-LDL-induced cellular toxicity and that inhibition of lipid peroxidation could be a key mechanism in the cytoprotective effect of these molecules.     

Screening of new chemopreventive compounds from Digitalis purpurea

Chemopreventive agents induce a battery of genes whose protein products can protect cells from chemical-induced carcinogenesis. In this study, we isolated four different glycosides (1 acteoside; 2 purpureaside A; 3 calceolarioside B; and 4, plantainoside D) from the leaves of Digitalis purpurea and studied their abilities to induce glutathione S-transferase (GST) and their protective efficiencies against aflatoxin B1-induced cytotoxicity in H4IIE cells. Of these four glycosides, acteoside significantly inhibited the cytotoxicity induced by aflatoxin B1 (AFB1) and also selectively increased GSTalpha protein levels. Reporter gene analysis using an antioxidant response element (ARE) containing construct and subcellular fractionation assays, revealed that GSTalpha induction by acteoside might be associated with Nrf2/ARE activation. The results suggest that acteoside possesses a potent hepatoprotective effect against AFB1 and that it can be applied as a potential chemopreventive agent.     

Relaxing effects of Ligstrum purpurascens extract and purified acteoside in rat aortic rings.

The present study describes the effects of an extract obtained from the leaves of Ligstrum purpurascens and acteoside purified from the extract on the contractile response to various agonists in rat isolated aortic rings. L. purpurascens extract relaxed 9,11-dideoxy-11 alpha,9 alpha-epoxymethanoprostaglandin F2 alpha (U46619)-preconstricted rings in a concentration-dependent manner (IC50: 0.14 +/- 0.01 mg/ml with endothelium and 0.16 +/- 0.01 mg/ml without endothelium). The extract also reduced contraction induced by 35 mM K+ or by 1 microM phorbol 12,13-diacetate (PDA) in endothelium-intact rings. The extract (0.1-0.3 mg/ml) reduced the concentration-response to U46619 in normal Krebs solution or to CaCl2 in 35 mM K(+)-containing solution. Acteoside accounts for 2.05% of total L. purpurascens extract in weight. Acteoside induced relaxation of rings preconstricted by U46619 (IC50: 0.22 +/- 0.01 mg/ml) but it caused an increase in 35 mM K(+)-induced tone. Removal of endothelium enhanced the relaxing effect of acteoside. Besides, pretreatment with acteoside inhibited endothelium/nitric oxide-mediated relaxation induced by acetylcholine. These results indicate that acteoside is unlikely the major ingredient responsible for the vasodilator effect of L. purpurascens extract. The extract relaxed the preconstricted aortic rings probably through multiple mechanisms by acting on smooth muscle cells. The inhibitory effect on endothelial nitric oxide-mediated relaxation suggests that acteoside could also act on the endothelial cells to reduce nitric oxide release.     

Role of oxidatively modified low density lipoproteins and anti-oxidants in atherothrombosis

Retrospective studies have demonstrated an association between coronary artery disease (CAD) and increased plasma levels of oxidised low density lipoproteins (LDL). A very recent prospective study in heart transplant patients has demonstrated that oxidised LDL is an independent risk factor for transplant CAD, thus further supporting the hypothesis that oxidised LDL is actively involved in the development of CAD. The increase of circulating oxidised LDL is most probably caused by back-diffusion from the atherosclerotic arterial wall in the blood, independent of plaque rupture. Indeed, plasma levels of oxidised LDL were very similar in patients with stable CAD and in patients with acute coronary syndromes. These were, however, associated with increased release of malondialdehyde (MDA)-modified LDL. Oxidised LDL may be generated by radical-mediated or by lipoxygenase or phospholipase catalysed lipid oxidation, and by myeloperoxidase catalysed protein and lipid oxidation. Prostaglandin synthesis by endothelial cells under oxidative stress and platelet activation are associated with the release of aldehydes; these induce the oxidative modification of the apolipoprotein B-100 moiety of LDL in the absence of lipid peroxidation, and thus generate MDA-modified LDL. Efficient prevention of in vivo oxidation may involve efficient cholesterol lowering, improving the anti-oxidative status of LDL by increasing the anti-oxidant content and increasing the oleate content of LDL, and by shifting the LDL away from phenotype B (characterised by small dense LDL particles). Anti-oxidative and anti-inflammatory enzymes associated with HDL may inhibit the oxidation of LDL or reverse the atherothrombotic effects of LDL.     

Role of oxidatively modified low density lipoproteins and anti-oxidants in atherothrombosis

Retrospective studies have demonstrated an association between coronary artery disease (CAD) and increased plasma levels of oxidised low density lipoproteins (LDL). A very recent prospective study in heart transplant patients has demonstrated that oxidised LDL is an independent risk factor for transplant CAD, thus further supporting the hypothesis that oxidised LDL is actively involved in the development of CAD. The increase of circulating oxidised LDL is most probably caused by back-diffusion from the atherosclerotic arterial wall in the blood, independent of plaque rupture. Indeed, plasma levels of oxidised LDL were very similar in patients with stable CAD and in patients with acute coronary syndromes. These were, however, associated with increased release of malondialdehyde (MDA)-modified LDL. Oxidised LDL may be generated by radical-mediated or by lipoxygenase or phospholipase catalysed lipid oxidation, and by myeloperoxidase catalysed protein and lipid oxidation. Prostaglandin synthesis by endothelial cells under oxidative stress and platelet activation are associated with the release of aldehydes; these induce the oxidative modification of the apolipoprotein B-100 moiety of LDL in the absence of lipid peroxidation, and thus generate MDA-modified LDL. Efficient prevention of in vivo oxidation may involve efficient cholesterol lowering, improving the anti-oxidative status of LDL by increasing the anti-oxidant content and increasing the oleate content of LDL, and by shifting the LDL away from phenotype B (characterised by small dense LDL particles). Anti-oxidative and anti-inflammatory enzymes associated with HDL may inhibit the oxidation of LDL or reverse the atherothrombotic effects of LDL.     

Acteoside protects endothelial cells against free radical-induced oxidative stress

The protective effect of acteoside against membrane lipid oxidation and free radical-mediated impairment of endothelial function was investigated. Results showed that iron-mediated oxidative modification of the cell membrane in cultured bovine pulmonary endothelial cells (PAECs) was significantly attenuated by acteoside as measured by thiobarbituric acid-reactive substances (TBARS). Fenton's reagent (H2O2/Fe2+) was used to generate hydroxyl radicals (*OH) and induce oxidative stress. Acteoside not only effectively minimized the loss of cell viability induced by hydroxyl radicals in cultured endothelial cells but also countered the free radical-induced destruction of the endothelium-dependent relaxation to acetylcholine in rat aorta. Furthermore, acteoside showed a dose-dependent scavenging effect of 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals and appeared to be the most efficient in comparison with the four reference compounds (alpha-tocopherol, vitamin C, probucol and resveratrol). These data suggested that acteoside protects the cell from oxidative stress and that scavenging of free radicals could be a key mechanism contributing to the cytoprotective effect of acteoside.     

用LC/ESI-MS/MS研究肉苁蓉与其代用品中的苯乙醇苷类化合物

目的　研究正品肉苁蓉及其习用品盐生肉苁蓉和管花肉苁蓉中的苯乙醇苷类化合物的种类和含量。方法　采用LC/ESI-MS/MS方法对正品肉苁蓉及其习用品盐生肉苁蓉和管花肉苁蓉中的7种苯乙醇苷类化合物进行定性分析及相对含量测定。结果　正品肉苁蓉中鉴别出7种苯乙醇苷类化合物;而盐生肉苁蓉中只含6种;管花肉苁蓉中只含5种, 而且3种肉苁蓉中苯乙醇苷含量也有差别。结论　3种肉苁蓉中苯乙醇苷类化合物的种类和含量是区别各种肉苁蓉的特征成分之一。     

有氧运动合用人参皂苷对饮食性高脂血症小鼠脂质代谢的影响(英文)

研究有氧运动及其合用人参茎叶皂苷（Ｇｉｎ）对饮食性高脂血症小鼠脂质代谢的影响。方法：通过喂养高胆固醇饲料２０天建立高脂血症模型,以无负重游泳作为有氧运动方式,观察有氧运动及其合用Ｇｉｎ时对高脂状态下小鼠的影响。结果：（１）高胆固醇饲料喂养２０天,小鼠血清ＴＣ,ＭＤＡ升高,ＨＤＬ－ｃ和ＳＯＤ降低,高脂血症模型建造成功,肝重量增加,有脂肪肝出现,胸腺重量减轻．（２）有氧运动降低ＴＣ,升高ＭＤＡ和ＨＤＬ－Ｃ,肝重量不减轻,脂肪肝存在．（３）有氧运动合用Ｇｉｎ时, ＴＣ, ＴＧ和 ＭＤＡ均降低（Ｐ＜ ０．０５）, ＨＤＬ－ｃ和ＳＯＤ显著升高（Ｐ＜０．０１）,肝重量减轻和胸腺重量接近正常,脂肪肝消失．结论：单纯有氧运动可在一定程度上降低血脂,但不能很好调节脂质代谢,当有氧运动合用Ｇｉｎ时,其降脂调脂和抗氧化作用才更明显,并可能有一定的减慢机体衰老过程的作用。     

Antioxidative effect of schisanhenol on human low density lipoprotein and its quantum chemical calculation

AIM: To investigate the effect of schisanhenol (Sal) on copper ion-induced oxidative modulation of human low density lipoprotein (LDL). METHODS: The antioxidative activity of eight schisandrins (DCL) on microsome lipid peroxidation induced by Vit C/NADPH system was first observed, and then, the effect of Sal on Cu^2 -induced human LDL oxidation was studied. The generation of malondialdehyde (MDA), lipofuscin, reactive oxygen species (ROS), consumption of α-tocopherol as well as electrophoretic mobility of LDL were determined as criteria of LDL oxidation. Finally, the quantum chemical method was used to calculate the theoretical parameters of eight DCL for elucidating the difference of their antioxidant ability. RESULTS: Sal was shown to be the most active one among eight schizandrins in inhibiting microsome lipid oxidation induced by Vit C/NADPH. Sal 100, 50, and 10 μmol/L inhibited production of MDA, lipofuscin and ROS as well as the consumption of α-tocopherol in Cu^2 -induced oxidation of human LDL in a dose-dependent manner. Sal also reduced electrophoretic mobility of the oxidized human LDL. Further study of quantum chemistry found that Sal was the strongest one among eight DCL to scavenge O^-.2, R‘, RO‘, and ROO radicals. CONCLUSION: Sal has antioxidative effect on human LDL oxidation. The mechanism of Sal against LDL oxidation may be through scavenging free radicals.