硒对甲型H1N1流感病毒感染小鼠的保护作用

目的:通过研究硒对流感病毒悬液滴鼻处理的小鼠的体重变化、死亡率、血清硒水平和细胞因子的影响,探讨硒对感染流感病毒小鼠的保护作用。方法:将60只昆明小鼠分为5组,每组12只,分别为缺硒组(0 mg/kg)、正常给硒组(0.2 mg/kg)、补充硒组(0.3 mg/kg)、补充硒组(0.4 mg/kg)、补充硒组(0.5 mg/kg)。给5周龄的小鼠滴鼻接种50μL的A/NWS/33(H1N1)病毒悬液并观察21天,监测每组小鼠的体重变化和死亡率;并在接种病毒后的第3天、第5天,检测小鼠的血清硒、TNF-α和IFN-γ水平。结果:缺硒组小鼠的死亡率高于正常给硒组和补充硒组(P0.05);缺硒组小鼠的血清硒水平明显低于正常给硒组和补充硒组(P0.05);在病毒感染第5天,缺硒组小鼠的TNF-α和IFN-γ含量低于正常给硒组和补充硒组(P0.05),差异均有统计学意义。结论:硒可以提高机体对抗流感病毒的免疫反应。     

硒缺乏与阿尔茨海默症

微量元素硒对维持中枢神经系统的生物功能具有重要作用。生物摄入硒后优先供给脑部。长期缺硒会引起包括阿尔茨海默症（AD）在内的脑疾病。AD的病理特征为β-．淀粉样肽聚集形成老年斑和tau蛋白过度磷酸化造成神经纤维缠结。氧化应激和信号转导紊乱在AD形成过程中具有重要作用。硒缺乏会影响AD发生发展的各个环节,与认知功能降低和AD形成密切相关。对近年有关硒与AD关系的研究进展进行综述,着重总结了硒缺乏对氧化应激、信号转导以及AD病理特征形成的作用和机制,探讨补硒延缓AD形成的可能性。     

微量元素硒在对抗COVID-19中的作用研究进展

自新型冠状病毒肺炎（corona virus disease 2019，COVID-19）疫情爆发以来，严重急性呼吸综合征冠状病毒2（severe acute respiratory syndrome-coronavirus 2， SARS-CoV-2）引起的各类临床表现和后续并发症受到了广泛关注。有研究发现，COVID-19死亡率具有地域差异性，中度或重度缺硒地区感染人群常常具有更高的死亡率，因此硒可能在对抗COVID-19中具有一定的作用。总结了硒缺乏COVID-19患者的临床表现、硒对抗COVID-19的临床效应、以及硒对抗COVID-19的作用机制等方面的研究进展。从目前的研究结果来看，硒在应对感染SARS-CoV-2以及避免过激免疫反应导致的细胞因子风暴过程中具有积极作用，但仍然缺乏临床试验研究证据。     

硒的生物地球化学研究团队介绍

<正>本课题组近10年来致力于土壤-植物体系中硒迁移转化及其生物有效性的研究。对陕西紫阳硒中毒区、青海平安富硒地区和泾惠灌区缺硒地区环境中硒及有效性进行了调研,系统研究了外源硒在土壤中环境过程及其影响硒有效性的因素;建立了形态和价态相结合的土壤硒测定方法,针对性地提出了评价硒有效性的指标,这些研究为硒有效性评价及缺硒地区硒的     

小白鼠硒蛋白的衰竭

硒蛋白在发育过程和成年期都发挥着关键作用,这种作用主要是通过其对细胞的酸碱平衡而产生的。但是,由于硒蛋白需要极少的微量营养物质和特化的转录机制,所以似乎不太适合应对氧化还原状态快速或急剧的变化。在本文中,作者检测了细胞是如何应对硒蛋白不是的。硝蛋白不足的状况可能是由于食物缺硒引起,也可能是由于斯它汀类药物造成的翻译抑制所致。     

长期缺硒对大鼠血浆氨基酸的影响

目的：探讨长期缺硒对大鼠血浆氨基酸的影响。方法：选取20只SPF级3 w龄雄性断乳Sprague-Dawley大鼠随机分为2组：对照组喂养正常饲粮（0.18 mg Se/kg）、缺硒组喂养低硒饲粮（0.02 mg Se/kg）。应用L-8900氨基酸分析仪检测血浆氨基酸水平。结果：第300天缺硒组大鼠血浆磷酸丝氨酸、牛磺酸、天门冬氨酸含量显著降低;第532天缺硒组大鼠血浆丝氨酸、缬氨酸、异亮氨酸、亮氨酸、苯丙氨酸、组氨酸含量显著升高,甘氨酸含量显著降低。结论：长期缺硒引起大鼠氨基酸代谢发生显著变化。     

细菌硒蛋白的研究进展

硒是人体必需的保健营养素,其在体内起到的活性作用主要源于硒蛋白;然而无机硒的摄入量存在上限问题,故给缺硒的机体寻找合适的有机硒蛋白已成为热点。本文主要介绍了已发现的硒蛋白,探讨了产硒蛋白的细菌种类及其表达机制,简述了硒蛋白的分离纯化技术,并归纳了硒蛋白的生物学功能,以期为今后硒蛋白的生产制备、有机硒产品的开发应用和医药保健的研究发展等方面提供有益的参考。     

硒胁迫下普氏原羚的采食对策

通过对青海湖湖东地区土壤和牧草矿物质元素含量的分析,发现该区严重缺硒.然而,生存于湖东地区的普氏原羚却不见缺硒表症,普氏原羚在长期的进化过程中适应了缺硒环境.提出假说:普氏原羚应对硒胁迫的主要对策是选择采食高硒植物, 在湖东地区,牧草硒含量是影响普氏原羚选择食物的主要因素.得出结论:在湖东地区,芨芨草是普氏原羚的基本食物,同时是主要的高硒植物.普氏原羚应对硒胁迫的主要对策是选择芨芨草草地作为采食地,增加高硒植物芨芨草在食物中的比例.也不是嗜食或喜食高硒植物.     

重新认识硒缺乏在雄性不育中的作用

饮食中缺乏硒可能引起雄性不育 ,因为硒缺乏会使精子中一种在结构上起重要作用的蛋白质功能减弱。硒缺乏与雄性啮齿类动物 ,还可能与家畜和人的不育有关。科学家通常相信 ,硒在这种保护精子免受氧化损伤的蛋白质中起着一个主要作用。Ｕｒｓｉｎｉ等发现 ,正在发育中的精子中含硒蛋白质确实执行着这样的功能 ,但精子发育成熟后 ,它的作用就完全不同了。这时 ,含硒蛋白质不与其它分子反应 ,而是构成用来储存精子线粒体的绝大多数物质重新认识硒缺乏在雄性不育中的作用@车笛     

硒的生物学功能及其补充剂的研究现状

硒是人体必需的、只能外源性补充的微量元素之一,人体缺硒可以导致癌症和多种疾病。本文阐述了硒的抗肿瘤、防衰老、抗氧化和增强机体免疫力等多种生物学功能,并概述了硒补充剂的研究现状,进而对硒补充剂的开发进行了展望。     

Effects of long-term selenium deficiency on glutathione peroxidase and thioredoxin reductase activities and expressions in rat aorta

The objective of this work was to determine whether long-term selenium (Se) deficiency might affect the antioxidant capacity of rat aorta, and the activities and expressions of glutathione peroxidase (GPx) and thioredoxin reductase (TR) in rat arterial walls. Weanling male Wister rats were fed Se-deficient or Se-adequate diets for 12 months. For the Se supplementation, sodium selenite was supplemented in drinking water (1 microg Se/ml) for 1 month. The aorta isolated from these groups were used to determine activities and mRNA levels. In comparison with the control, the activity and expression of GPx, superoxide dismutase activity and the total antioxidant capacity were significantly decreased in Se-deficient rats arterial walls. Following Se supplementation, they were restored to different extents. The content of malondialdehyde was increased markedly in Se-deficient rats. There seems an inverse relationship between the dietary Se and the activity and expression of TR. A positive relationship exists between dietary Se and the antioxidant capacity of rat arterial walls. The activities and expressions of GPx and TR in arterial walls were regulated by selenium by different mechanisms. Regulation of the expression of TR was mediated by reactive oxygen species, but of GPx by selenium status. The thioredoxin system may be the major cellular redox signaling system in rat arteries, rather than the glutathione system.     

Selenium deficiency induced damages and altered expressions of metalloproteinases and their inhibitors (MMP1/3, TIMP1/3) in the kidneys of growing rats

Selenium is an essential trace element for the maintenance of structures and functions of kidney. To evaluate the effects of low selenium on the kidneys of growing rats, newborn rats were fed with selenium deficient and normal diets respectively for 109 days. As a result, rats fed with low selenium diets resulted in a decline in the body weight and the concentration of selenium in the kidney, especially the male rats from the low selenium groups. Moreover, the ultrastructure of glomerulus and tubules were damaged in low selenium group: the glomeruli were observed with hyperplasia of mesangial cells, fusion of podocyte foot processes and thickening of basement membrane; and the tubules were observed with vacuolar degenerated epithelial cells, increased edema fluid or protein solution between cells, microvilli edema, increased cell gaps and decreased cell links. Furthermore, the pathological changes in selenium deficient group included the increase of fibers around renal hilum aorta and in the renal collecting duct, and shed of cells in the proximal convoluted tubules. In addition, up-regulated expressions of matrix metalloproteinases (MMP1/3) and down-regulated expressions of their inhibitors (TIMP1/3) at the mRNA and protein levels were also appeared to be relevant to low selenium. The results suggested that low selenium in diet may cause low selenium concentration in the kidney of growing rat and lead to damages of the ultrastructure and extracellular matrix (ECM) of kidney.     

Novel enrichment of tumor cell transfectants expressing high levels of type 4 glutathione peroxidase using 7alpha-hydroperoxycholesterol as a selection agent

A novel approach for selecting high expressing cells out of a general population that had been transfected with a construct encoding cytosolic type 4 glutathione peroxidase (GPx4) is reported. The approach is described for GPx4-null COH-BR1 breast tumor cells and is based on use of a highly specific GPx4 substrate, 7alpha-hydroperoxycholesterol (7alpha-OOH), as a selection agent. Cells recovering from a highly toxic dose of liposomal 7alpha-OOH were found to be substantially more resistant to a second 7alpha-OOH challenge than cells recovering from a less toxic dose, but were much less resistant to t-butyl hydroperoxide (t-BuOOH) or H(2)O(2). Several clones isolated from the general transfectant population exhibited variable, relatively low GPx4 activities. However, clones from the 7alpha-OOH-selected population exhibited uniformly high GPx4 activities (each approximately 3-fold higher than that of the starting transfectant population) and elevated steady-state mRNA levels. t-BuOOH could also be used for selecting high GPx4-expressing cells, but consistent recovery from toxic doses was more difficult than with 7alpha-OOH. Compared with conventional "hit or miss" cloning procedures, the 7alpha-OOH approach we describe affords a uniform population of high GPx4-activity cells in a relatively rapid manner. This approach should prove valuable for investigators interested in the peroxide regulatory properties of GPx4, in the context of both cytoprotection and redox signaling.     

Glutathione peroxidase activities during selenium depletion of adult female rats and during selenium repletion of their offspring

The main purpose of the present investigation was to produce young rats with severe selenium deficiency, but with no clinical signs of this deficiency, and to examine their liver and red blood cell (RBC) glutathione peroxidase activities during selenium repletion. To achieve this goal, female breeders were fed a selenium-deficient diet beginning 2 weeks before mating. The liver glutathione peroxidase activity of the dams was significantly lower than the activity of comparable nonpregnant females after 5 and 10 weeks of selenium depletion. This difference arose exclusively during the period of pregnancy. In contrast, the RBC glutathione peroxidase activity was significantly increased during this period. Only traces of liver enzyme activity were found in the offspring, and the RBC enzyme activity was only 2% of that of the selenium-repleted controls. Body weight was retarded in the male offspring. However, no severe signs of clinical selenium deficiency were observed. The glutathione peroxidase activity in the liver and RBCs of the offspring was determined after 0, 2, 4, 7, 14, and approximately 40 days of selenium repletion. The liver enzyme activity increased faster in females than in males, while the opposite was found for the RBCs. After 14 days of selenium repletion, the glutathione peroxidase activity of the liver was essentially restored, and the RBC enzyme activity was about half that of the control values. This type of rat may prove useful in studies in which young selenium-deficient rats are preferable, as well as in studies of selenium functions that might not be directly related to the role of selenium in glutathione peroxidase.     

A histochemical study about changes in rat liver plasma membrane enzyme activities after galactosamine administration.

In rats changes in plasma membrane enzyme activities due to Gal-N intoxication were studied by enzymehistochemical methods. The bile canalicular 5'-nucleotidase and nucleoside polyphosphatase activities decreased; the sinusoidal 5'-nucleotidase remained unchanged. The bile canalicular leucyl-beta-naphthyl-amidase showed an increase in activity; the alkaline phosphatase activity remained unchanged. In contrast to the spotty necrosis, changes in plasma membrane enzyme activities were seen in all liver cells, suggesting that changes of these activities, occurring after Gal-N treatment, do not correlate with cell death. The conclusion was drawn that the deviations of the enzyme activities might be due to changes in the lipid environment of the enzyme proteins in the membrane. With the exception of alkaline phosphatase, partial hepatectomy caused the same changes in enzyme activities as did Gal-N intoxication. Nevertheless Gal-N administration to partial hepatectomized rats did not lead to hepatic necrosis. Galactose given simultaneously or within two hours after Gal-N prevented both changes in plasma membrane enzyme activities and hepatocellular damage. This suggests an important role of galactolipids and galactoproteins in the plasma membrane alterations.     

Aldehyde and Xanthine Oxidase Activities in Tissues of Streptozotocin-Induced Diabetic Rats: Effects of Vitamin E and Selenium Supplementation

Effects of vitamin E and selenium supplementation on aldehyde oxidase (AO) and xanthine oxidase (XO) activities and antioxidant status in liver, kidney, and heart of streptozotocin (STZ)-induced diabetic rats were examined. AO and XO activities increased significantly after induction of diabetes in rats. Following oral vitamin E (300 mg/kg) and sodium selenite (0.5 mg/kg) intake once a day for 4 weeks, XO activity decreased significantly. AO activity decreased significantly in liver, but remained unchanged in kidney and heart of vitamin E- and selenium-treated rats compared to the diabetic rats. Total antioxidants status, paraoxonase-1 (PON1) and erythrocyte superoxide dismutase activities significantly decreased in the diabetic rats compared to the controls, while a higher fasting plasma glucose level was observed in the diabetic animals. The glutathione peroxidase activity remained statistically unchanged. Malondialdehyde and oxidized low-density lipoprotein levels were higher in the diabetic animals; however, these values were significantly reduced following vitamin E and selenium supplementation. In summary, both AO and XO activities increase in STZ-induced diabetic rats, and vitamin E and selenium supplementation can reduce these activities. The results also indicate that administration of vitamin E and selenium has hypolipidemic, hypoglycemic, and antioxidative effects. It decreases tissue damages in diabetic rats, too.     

Supplementation of vitamin E and selenium prevents hyperoxaluria in experimental urolithic rats

Renal injury is considered as one of the prerequisites for calcium oxalate retention. In order to determine the role of lipid peroxidation related effects for hyperoxaluria, we evaluated the alterations in lipid peroxidation, antioxidants and oxalate synthesizing enzymes in lithogenic rats with response to vitamin E + selenium treatment. In kidney of lithogenic rats, the level of lipid peroxidation and the activities of oxalate synthesizing enzymes were found to be increased whereas the levels/activities of non-enzymatic and enzymatic antioxidants were found to be decreased. The urinary excretion of both oxalate and calcium were significantly elevated. Supplementation of lithogenic rats with vitamin E + selenium decreased the levels of lipid peroxides and the activities of oxalate synthesizing enzymes like glycolic acid oxidase (GAO), lactate dehydrogenase (LDH), xanthine oxidase (XO) with a concomitant increase in the activities of enzymatic antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PDH) and increased levels of non-enzymatic antioxidants like ascorbic acid, alpha-tocopherol and reduced glutathione (GSH). The urinary excretion of oxalate and calcium were normalized. The antioxidants vitamin E + selenium thereby protected from hyperoxaluria.     

Kinetics and mechanisms of oxidation of some antioxidants with photochemically generated tert-butoxyl radicals

Dietary antioxidants play an important role in the prevention of several chronic diseases including cardiovascular diseases, cancer, ageing and diabetes. In order to understand the mechanism of oxidation of antioxidants viz., gallic acid (GA), caffeic acid (CA), rosmarinic acid (RA) and chlorogenic acid (CGA), a systematic kinetic study of these antioxidants with photochemically generated tertiary butoxyl (t-BuO) radicals was carried out. The oxidation of antioxidants by t-BuO radicals was followed spectrophotometrically by measuring the absorbance of GA (266 nm), CA (310 nm), RA (324 nm) and CGA (328 nm) at their respective lambda(max). The initial rates of oxidation of antioxidants were calculated from the plot of absorbance vs time and were found to increase with increase in [antioxidant], [t-BuOOH] and light intensity in all the cases. The quantum yields (phi) were calculated from the initial rates of oxidation of antioxidant and the measured light intensity at 254 nm, the wavelength at which the tert-butyl hydroperoxide (t-BuOOH) was activated to radicals. The quantum yields were found to depend on [antioxidant] and [t-BuOOH], and were independent of light intensity. The order with respect to [antioxidant], [t-BuOOH] were found to be fractional whereas order with respect to intensity was one. The order of reactivity was found to be: CA > CGA > RA > GA. The products were identified by mass spectral data. On the basis of kinetic results and product analysis, probable mechanisms were suggested.     

Selenium supplementation sensitizes renca cells to tert-butylhydroperoxide induced loss of viability

Mouse renal carcinoma (renca) cells growing exponentially in foetal bovine serum (1%) supplemented with selenium (1 microM, sodium selenite) were exposed to oxidative insult. It was found that glutathione peroxidase activity increased (44%), while the activities of catalase, glutathione disulfide reductase, and level of total glutathione did not change due to selenium supplementation. Selenium supplementation made renca cells susceptible to tert-butylhydroperoxide induced cell death, while it did not affect the viability when the cells were exposed to hydrogen peroxide. It suggested that the contribution of glutathione peroxidase in antioxidant defense mechanism of renca cells was possibly not crucial and the function of catalase might be important especially against hydrogen peroxide.     

Cytoprotection against lipid hydroperoxides correlates with increased glutathione peroxidase activities, but not selenium uptake from different selenocompounds

Cells cultivated under standard conditions were highly deficient in tocopherol, selenium, and glutathione peroxidase (GPx) activities. We investigated whether and to what extent the addition of different selenocompounds to growth media would alter biochemical, physiological, and pathophysiological parameters of cultured liver cells. Cellular uptake of selenium, GPx activities, and cytoprotection were measured and compared in human hepatoma cells (HepG2). Selenite and selenocystine were Se donors of high bioavailability (i.e., with these culture supplements, the increased Se uptake, induction of GPx isoenzymes, and protection of treated cells from lipid hydroperoxides were well correlated). In contrast, selenium from selenomethionine was incorporated into cellular proteins but had no effect on GPx activities or cytoprotection. The data show that not all selenium donors provide selenium, which is bioactivated to act as antioxidant. Thus, cellular selenium content, in general, did not correlate with cytoprotective activity of this trace element. However, cellular GPx activities at different times, with different concentrations, and with different Se donors always correlated with protection from lipid hydroperoxides and may, thus, represent a more reliable parameter to define adequate Se supply.