硒和维生素E不足对大鼠血液流变学影响初探

本实验研究了硒（Ｓｅ）和维生素Ｅ（ＶＥ）对大鼠血液流变学、血栓素（ＴＸＡ２）、前列环素（ＰＧＩ２）的影响。结果表明，饲以低Ｓｅ和低ＶＥ粮大鼠红细胞变形性、ＰＧＩ２水平降低，红细胞压积、红细胞聚集性、红细胞聚集指数、ＴＸＡ２水平、ＴＸＡ２／ＰＧＩ２比值升高，谷胱甘肽过氧化物酶和超氧化物歧化酶活力降低，脂质过氧化物含量增高。补充Ｓｅ或ＶＥ及Ｓｅ＋ＶＥ对纠正上述变化有相似而又不尽相同的效果，以联合补充效果好。结果提示，Ｓｅ和ＶＥ不足可能通过两个途径：（１）间接途径─—花生四烯酸代谢产物ＴＸＡ２、ＰＧＩｅ水平；（２）直接途径──Ｓｐｅｃｔｒｉｎ与红细胞变形性，影响血液流变性能及微循环功能，可能参与缺血缺氧性心肌损害的发病环节。     

硒对高胆固醇血症家兔血液流变性的影响

对高胆固醇血症家兔应用硒（Ｓｅ）后血液流变性、过氧化脂质（ＬＰＯ）、谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）和超氧化物歧化酶（ＳＯＤ）、血栓素（ＴＸＡ２）、前列环素（ＰＧＩ２）进行观察。发现Ｓｅ可不同程度降低高胆固醇家兔红细胞压积和红细胞聚集性,增加红细胞变形性,降低血清ＬＰＯ含量、ＴＸＡ２／ＰＧＩ２比值和ＴＸＡ２水平,提高ＧＳＨ－Ｐｘ、ＳＯＤ活力和ＰＧＩ２水平。提示Ｓｅ有降低血液粘稠度作用     

补硒对低硒居民血小板活化状态的影响

应用１２５Ｉ标记放免法测定血浆血栓素（ＴＸＡ２）、前列环素（ＰＧＩ２）和血小板ＴＸＡ２生成，以比浊法和ＥＬＩＳＡ分别测定血小板聚集性和β－血小板球蛋白（βＴＧ），电镜观察血小板形态，对比研究补硒（２００μｇＳｅ／ｄ，亚硒酸钠，１２周）和未补硒低硒居民上述参数的变化。用２，３－二氨基萘荧光法和谷胱甘肽还原酶偶联法测定硒含量和谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）活性。结果表明，补硒使红细胞硒和ＧＳＨ－Ｐｘ活性显著增高（Ｐ＜０．０１）；血浆ＴＸＡ２、ＴＸＡ２／ＰＧＩ２比值及血小板ＴＸＡ２生成和聚集性均显著低于未补硒组（Ｐ＜０．０１或０．０５），但血浆ＰＧＩ２和βＴＧ含量以及血小板βＴＧ含量和释放率无显著改变（Ｐ＞０．０５）；补硒可明显减轻病区低硒居民血小板的形态变化，使α－颗粒数显著高于未补硒组（Ｐ＜０．０１）；红细胞硒或ＧＳＨ－Ｐｘ活性分别与血浆ＴＸＡ２和血小板ＴＸＡ２生成呈显著负相关（ｒ＝－０．６９６，－０．７８０；－０．６７６和－０．７９６，Ｐ＜０．０１），与ＡＤＰ诱导的血小板聚集性显著负相关（ｒ＝－０．３９０，－０．３７２，Ｐ＜０．０５）；与凝血酶诱导的聚集性呈不显著的负相关（ｒ＝－０．２７９，－０．３０９?     

硒和/或维生素E预防大鼠内皮细胞损伤的实验研究

用含硒（Ｓｅ０．５ｍｇ／ｋｇ）和／或维生素Ｅ（ＶＥ０．６ｇ／ｋｇ）的高脂饲料喂养成年雄性Ｗｉｓｔａｒ大鼠１２周。结果：高脂对照组大鼠血浆前列腺素Ｆｌα（６－酮－ＰＧＦ１α）水平下降，而血清脂质过氧化物（ＬＰＯ）、血浆血栓素（ＴＸＢ２）及内皮素（ＥＴ）水平上升；补Ｓｅ、ＶＥ及Ｓｅ＋ＶＥ可明显降低大鼠血清ＬＰＯ、血浆ＴＸＢ２、ＥＴ及ＴＸＢ２／６－酮－ＰＧＦ１α比值。同时，除了明显提高血浆谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）活力外，血浆６－酮－ＰＧＦ１α浓度明显升高。实验提示，Ｓｅ和／或ＶＥ有调节花生四烯酸代谢及保护内皮细胞的作用。     

月见草油对实验性高脂血症脂质过氧化、血浆TXA2、PGI2及ET水平的影响

用含２％月见草油的高脂饲料喂饲实验性高脂血症大鼠４周，分别对血脂、血清脂质过氧化物（ＬＰＯ）、血浆超氧化物歧化酶（ＳＯＤ）、血栓素（ＴＸＡ２）、前列腺素（ＰＧＩ２）及内皮素（ＥＴ）进行了检测，并用扫描电镜对动脉内皮进行了观察。结果发现：月见草油能降低血清总胆固醇（ＴＣ）及甘油三酯（ＴＧ）含量，提高高密度脂蛋白胆固醇（ＨＤＬ－Ｃ）含量；月见草油能显著降低血清ＬＰＯ水平，提高血浆ＳＯＤ活力；月见草油组大鼠血浆ＰＧＩ２水平明显增高，而ＴＸＡ２／ＰＧＩ２比值及血浆ＥＴ水平明显下降；月见草油组大鼠肝脏脂肪蓄积稍轻于高脂对照组；扫描电镜观察亦发现月见草油组大鼠动脉内皮损伤明显轻于高脂对照组。结果提示月见草油具有良好的降脂、保护内皮细胞及预防动脉粥样硬化形成的作用     

吸烟对口服避孕药妇女血栓栓塞性疾病的影响

口服避孕药（ＯＣ）通过影响凝血活性增加血栓栓塞性疾病的危险。吸烟是血管疾病的另一危险因素,影响前列环素（ＰＧＩ２）、血栓素Ａ２（ＴＸＡ２）的形成及对血管内皮起作用。吸烟的同时服用ＯＣ可进一步啬血栓栓塞性疾病的危险,危险性大小与ＯＣ中乙炔雌二醇（ＥＥ）的含量、吸烟量呈正相关,而静脉血栓的发生与孕激素种类有关。     

儿童血压与尿中TXB_2、PGI_2排出量关系的探讨

采用病例－对照的研究方法，对济南市区６所小学的８～１０岁血压偏高的儿童进行了４ｈ尿中血栓素Ｂ２（ＴＸＢ２）、前列环素（ＰＧＩ２，放射免疫法）排出量的对比观察。结果发现，血压偏高组儿童尿中ＴＸＢ２排出量高于血压正常组，而ＰＧＩ２排出量则低于血压正常组。单因素相关分析结果，儿童血压（收缩压）与尿中ＴＸＢ２排出量呈正相关（ｒ＝０．２２，Ｐ＜０．０５）与ＰＧＩ２的排出量呈负相关（ｒ＝－０．２５，Ｐ＜０．０５）。提示儿童血压与尿中ＴＸＢ２、ＰＧＩ２排出量有着重要关系。     

脂肪乳剂Intralipid对急性肺损伤兔前列腺素低谢及其功能的影响

为研究脂肪乳剂对急性肺损伤兔前列腺素代谢的影响，我们对实验动物予以肠外营养，持续静脉输注脂肪乳剂４８ｈ。结果糖脂组血中及支气管肺泡灌洗液中血管紧张素转化酶、超氧化物岐化酶含量明显下降，前列环素、血栓素及其ＰＧＩ２／ＴＸＡ２比值有明显升高，灌洗液中细胞计数糖脂组明显下降。     

高脂血症患者前列环素,血栓素及D—二聚体的检测与分析

采用放射免疫法和ＥＬＩＳＡ法测定了６９例高脂血症患者６－酮－前列腺素Ｆ１α（６－Ｋ＝ＰＧＦ１α）、血栓素Ｂ２（ＴＸＢ２）以及Ｄ－二聚体（Ｄ－ｄｉｍｅｒ）和纤维蛋白（原）降解产物（ＦＤＰ）,并与２０例正常人比较。结果发现是血症患者６－Ｋ－ＰＧＦ１α低于对照组（Ｐ〈０．０５）,ＴＸＢ２高于对照组（Ｐ〈０．０１）,同时,Ｄ－ｄｉｍｅｒ和ＦＤＰ也高于对照组（Ｐ〈０．００１）。高脂血症患者体内处于ＰＧＩ２／     

硒、维生素E对心肌胶原蛋白代谢的影响

目的：阐明硒（Ｓｅ）、维生素Ｅ（ＶＥ）与心肌胶原蛋白代谢的关系。方法：以病区粮（低Ｓｅ、低ＶＥ）喂养大鼠,并注射异丙基肾上腺素（ＩＳＯ）诱发心肌缺血缺氧性坏死,检测心肌中谷胱甘肽氧化酶（ＧＳＨ－ＰＸ）、过氧化氢酶（ＣＡＴ）、丙二醛（ＭＤＡ）和胶原蛋白含量变化。结果：低Ｓｅ低ＶＥ组血浆和心肌ＧＳＨ－ＰＸ、ＣＡＴ活性下降,ＭＤＡ含量上升,与心肌胶原蛋白含量变化有相关性。补Ｓｅ补ＶＥ后,ＧＳＨ－ＰＸ、ＣＡＴ活性上升,ＭＤＡ水平下降,心肌胶原蛋白含量下降。结论：低Ｓｅ低ＶＥ加重ＩＳＯ诱发的心肌损伤,脂质过氧化和自由基与心肌胶原蛋白代谢关系密切。补Ｓｅ补ＶＥ后,能缓解心肌细胞对诱发因素所造成的损伤,对保护心肌细胞和防止心肌纤维化的形成具有一定作用。     

Lung eicosanoid synthesis is affected by age, dietary fat and vitamin E.

The effect of age, dietary fat type and all-rac-alpha-tocopheryl acetate (vitamin E) supplementation on ex vivo synthesis of lung eicosanoids was measured in C57BL/6NIA mice using a 2 (age) x 3 (fat) x 3 (vitamin E) factorial design. Young (3-mo-old) and old (24-mo-old) mice were fed a semipurified diet containing 5% (by wt) corn oil, coconut oil or fish oil supplemented with 30, 100 or 500 mg vitamin E/kg for 4 wk. Ex vivo synthesis of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (PGI2) were measured by RIA in lung homogenates. Old mice had significantly higher concentrations of TXB2 and PGI2 than did young mice, resulting in a significant increase in the TXB2:PGI2 ratio with aging. Young and old mice fed fish oil had significantly lower concentrations of PGI2 and TXB2 than those fed corn oil or coconut oil. The degree of reduction varied according to age and vitamin E status. Old mice fed fish oil and 30 mg vitamin E/kg diet had the lowest plasma vitamin E concentration and the highest TXB2:PGI2 ratio. The TXB2:PGI2 ratio was significantly reduced in old mice fed coconut oil or fish oil by vitamin E supplementation. Vitamin E supplementation (100 mg/kg) significantly increased PGI2 concentration in young mice fed coconut oil. Thus, significant changes in the capacity of lung to synthesize eicosanoids occur with age and are influenced by dietary fat type and vitamin E. J. Nutr.     

氧化固醇对不同硒状态大鼠前列环素和内皮素的影响

目的 :　研究不同硒量下氧化固醇对血浆前列环素 (PGI2 )和内皮素 (ET)水平的影响。方法 :　采用低硒饲料饲养大鼠 1 3 w后 ,从尾静脉注射氧化固醇 (Ch- Ox) 3 β,5 α,6 β-三羟胆固醇 (3 - triol) ,2 4 h后采用放射免疫法测定其血浆 PGI2 、血栓烷 A2 (TXA2 )和 ET水平。结果 :　低硒组血硒含量及谷胱甘肽过氧化物酶 (GSH- Px)活性显著低于对照组 (P<0 .0 1 ) ,血浆 PGI2 水平也显著低于对照组 (P<0 .0 5 ) ,但其血浆脂质过氧化物 (LPO)水平及血浆 TXA2 水平显著高于对照组 (P<0 .0 5和 P<0 .0 1 ) ,从而导致 PGI2 /TXA2 比值显著低于对照组 (P<0 .0 1 )。对照 +3 -triol组血浆 PGI2 、TXA2 及 PGI2 /TXA2 与对照组相比均无显著性差异。虽然低硒 +3 - triol组血浆PGI2 与对照 +3 - triol组相比无显著性差异 ,但其血浆 TXA2 显著高于对照 +3 - triol组 (P<0 .0 0 1 )。低硒组与对照组相比 ,血浆 ET水平略有降低 ,差异不显著。对照组注射 3 - triol后血浆 ET水平显著升高 (P<0 .0 5 ) ,而低硒组注射 3 - triol后血浆 ET显著低于对照 +3 - triol组 (P<0 .0 5 )。给低硒 1 0 w的大鼠饮水补硒可一定程度上减小这些变化。结论 :　低硒和 Ch- Ox影响 PGI2 、TXA2 的浓度 ,使 PGI2 /TXA2 比值降低 ,Ch- Ox还使     

Differential effects of dietary vitamin E and antioxidants on eicosanoid synthesis in young rabbits

This study was designed to evaluate the effects of dietary vitamin E and synthetic antioxidants on prostacyclin (PGI2) synthesis in isolated aorta segments and perfused hearts as well as thromboxane (TxA2) synthesis in thrombin-stimulated washed platelets. Weanling male New Zealand rabbits were fed a vitamin E-deficient basal diet or the basal diet supplemented with either all-rac-alpha-tocopherol acetate or propyl gallate or DPPD (N,N'-diphenyl-p-phenylenediamine). After 30 days on the diet, plasma tocopherol level, pyruvate kinase and liver microsomal NADPH oxidase were determined. DPPD but not propyl gallate prevented the development of myopathy. None of the synthetic antioxidants could substitute for vitamin E in decreasing enzymatic lipid peroxidation. PGI2 release by the aorta was lowered in vitamin E deficiency and was highest with DPPD supplementation. In the Langendorff perfused heart, however, PGI2 release was highest in the vitamin E-deficient group, possibly due to cardiomyopathy. TxA2 synthesis by washed platelets challenged with thrombin was independent of the antioxidant status of the animal. The data showed that dietary antioxidants selectively affect eicosanoid synthesis in different tissues.     

Vitamin E increases production of vasodilator prostanoids in human aortic endothelial cells through opposing effects on cyclooxygenase-2 and phospholipase A2

Impairment of endothelium-dependent vasodilation is associated with the initiation and development of atherosclerosis. Vasodilator prostanoids constitute a protective mechanism in maintaining normal vasomotor function. In the current study, we determined the effect of in vitro vitamin E supplementation at physiologically relevant concentrations (10-60 micromol/L) on the production of the vasodilator prostanoids prostaglandin I(2) (PGI(2); prostacyclin) and prostaglandin E(2)(PGE(2)) by human aortic endothelial cells (HAECs) as well as its underlying mechanism. Results showed that vitamin E dose dependently (10-40 micromol/L) increased the production of both prostanoids by HAECs. This was associated with a dose-dependent (10-40 micromol/L) upregulation of cytosolic phospholipase A(2) (cPLA(2)) expression and arachidonic acid release. In contrast, vitamin E dose dependently (10-60 micromol/L) inhibited cyclooxygenase (COX) activity but did not affect the expression of either COX-1 or COX-2, indicating that the effect of vitamin E on COX activity was post-translational. Thus, vitamin E had opposing effects on the 2 key enzymes in prostanoid biosynthesis; at the concentrations used in this study, this resulted in a net increase in the production of vasodilator prostanoids. The vitamin E-induced increase in PGI(2) and PGE(2) production may contribute to its suggested beneficial effect in preserving endothelial function.     

硒在前列环素生物合成中作用机制的研究

目的　评价硒在前列环素生物合成中的作用机制。方法　用低硒饲料、补硒饲料和常规饲料饲养雄性大鼠 1 4周后 ,测定血液和某些组织中硒、前列环素 ( PGI2 )、血栓素 ( TXA2 )和脂质过氧化物 ( LPO)的含量 ,谷胱甘肽过氧化物酶 ( GSH- Px)活性及前列腺素内过氧化物合成酶( PGHS)的过氧化物酶活性 ,并采用 RNA折叠程序对 3个前列环素合成酶 ( PGIS)基因 3 非翻译区 ( UTR)的二级结构进行计算机预测 ,与已知的 39个真核生物硒蛋白基因的硒代半胱氨酸插入序列 ( SECIS)进行比较。结果　低硒大鼠血浆 PGI2 浓度、血和组织中硒含量及 GSH- Px活性显著下降 ,LPO水平升高 ,但三组之间血浆 TXA2 水平和组织中 PGHS-过氧化物酶活性均无显著差异 ,在 PGIS基因中未见到硒蛋白所特有的 SECIS。结论　PGIS可能不是硒酶 ,硒可能是通过 GSH-Px或其他硒蛋白抑制过氧化物的产生而影响 PGI2 的合成     

2型糖尿病并糖尿病足患者中血栓素A2、前列环素的变化及临床意义

目的探讨2型糖尿病(T2DM)合并糖尿病足(DF)患者血栓素A2(TXA2)和前列环素(PGI2)的变化情况及其与糖尿病足病情的关系。方法 60例T2DM并DF患者分为DF非坏疽组38例和DF坏疽组22例,30例健康体检者为对照组,应用放免法测定血浆TXA2和PGI2的稳定代谢产物血栓素B2(TXB2)和6-酮-前列环素(6-keto-PGF1α)含量,同时观察DF患者的病程、体质指数、血压、血糖、胰岛素、糖化血红蛋白、血脂、胰岛素抵抗指数(HOMA-IR)和踝肱动脉指数(ABI)的变化,并分析其与TXB2和6-keto-PGF1α的关系。结果糖尿病患者存在明显的TXA2和PGI2平衡异常。糖尿病足患者的血浆TXB2明显高于对照组(P<0.01),而血浆6-keto-PGF1α水平明显低于对照组(P<0.01),糖尿病足患者的TXB2/6-keto-PGF1α(T/P)明显高于对照组,DF坏疽组比DF非坏疽组更为严重(P<0.01)。糖尿病足组患者的T/P值与病程、总胆固醇、低密度胆固醇、空腹血糖、餐后2小时血糖和HOMA-IR呈正相关关系(P<0.05,P<0.01),与ABI呈负相关关系(P<0.01)。结论检测血浆TBA2与6-keto-PGF1α水平可提示血管内皮细胞的损伤,早期判断糖尿病足患者血管病变的程度,及早采取治疗措施。     

Vitamin E improves microsomal phospholipase A2 activity and the arachidonic acid cascade in kidney of diabetic rats

The purpose of the present study was to investigate the effects of vitamin E on microsomal phospholipase A2 activity and the arachidonic acid cascade in the kidneys of streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley male rats weighing 100 +/- 10 g were randomly assigned to one normal and three STZ-induced diabetic groups. The diabetic groups were fed a vitamin E-free diet (the DM-0E group), 40 mg vitamin E/kg diet (the DM-40E group) or a 400 mg vitamin E/kg diet (the DM-400E group). The kidney vitamin E concentrations were 59 and 49% lower in the DM-0E and DM-40E groups, respectively, than in the normal group. The kidney thiobarbituric acid reactive substance concentrations in the DM-0E, DM-40E and DM-400E groups were 119, 84 and 33% greater, respectively, than that in the normal group. The concentration in the DM-400E group was 39% lower than that in the DM-0E group. The phospholipase A2 (PLA2) activity in the kidney microsomes of the DM-0E-40E and DM-400E groups were 88, 58 and 35% greater, respectively, than that in the normal group. The activity in the DM-400E group was 28% lower than that in the DM-0E group and 16% lower than that in the DM-40E group. The differences in the phospholipids in the kidney microsomes included reductions in the phosphatidylcholine and phosphatidylethanolamine compositions. Phosphatidylethanolamine hydrolysis in the kidney microsomes of the DM-0E and DM-40E groups were 84 and 64%, which did not differ from the DM-400E group. The formation of thromboxane A2 (TXA2) in the kidney microsomes was 137 and 70% greater in the DM-0E and DM-40E groups, respectively, than in the normal group. TXA2 formation did not differ between the DM-400E and normal groups. The formation of prostacyclin in the kidney microsomes was 60 and 44% lower in the DM-0E and DM-40E groups, respectively, than in the normal group, whereas the DM-400E group did not differ from that in the normal group. The ratio of prostacyclin to TXA2 was 82 and 65% lower than normal in the DM-0E and DM-40E groups, respectively. Kidney function appears to be improved by vitamin E supplementation due to its antithrombus action, which in turn controls the arachidonic acid cascade system.