ω-3脂肪酸与冠状动脉性心脏病

ω-3多不饱和脂肪酸对冠状动脉性心脏病有潜在的预防和治疗作用，其保护心血管的可能作用机制包括：（1）抗心律失常；（2）调节脂代谢；（3）延缓动脉粥样硬化斑块的发展。     

人参皂苷Rg1对神经保护作用机制的研究进展

本文就人参皂苷Rg1对突触的保护、对钙通道拮抗作用、对谷氨酸（GLU）和γ-氨基丁酸（GABA）的影响、抗氧化、抗自由基、抗凋亡及抗应激作用、雌激素样作用、对一氧化氮（NO）及一氧化氮合酶（NOS）的影响、抑制脑神经细胞凋亡、稳定生物细胞膜和改善线粒体功能障碍、对神经递质的影响及抑制神经毒性作用机制的研究现状进行了阐述，旨在为今后的研究及治疗神经退行性疾病提供借鉴。     

西玛津调控SPAG6介导AP - 1转录活性对小鼠生精细胞凋亡的影响

目的 研究与探讨西玛津对小鼠精母细胞（GC - 2 spd）增殖的影响及作用机制。方法 COS - 7细胞共转染pAP1 - luc和Spag6基因的表达质粒，荧光素酶报告基因实验检测SPAG6对AP - 1转录活性的影响。以不同浓度西玛津（0、5、25、125 μg/mL）染毒GC - 2 spd细胞24、48和72 h，采用CCK - 8法检测细胞存活率。西玛津染毒24 h后，western blot检测SPAG6和COPS5蛋白的表达变化，qPCR检测促凋亡因子Bax及抗凋亡因子Bcl - 2 mRNA的表达。结果 COS - 7细胞内过表达SPAG6能抑制AP - 1的转录活性。与对照组比较，25和125 μg/mL西玛津染毒组中GC - 2 spd细胞存活率、细胞内SPAG6蛋白及Bax mRNA的表达水平均下降，差异具有统计学意义（P＜0.05），然而COPS5蛋白及Bcl - 2 mRNA的表达没有显著变化，差异无统计学意义（P＞0.05）。结论 西玛津对GC - 2 spd细胞具有毒性作用，可能通过抑制SPAG6蛋白表达从而调节AP - 1介导的凋亡基因的表达，诱导生精细胞凋亡。     

枸杞多糖粗品抗突变作用的研究

目的研究枸杞多糖粗品（LBPc）对遗传损伤的保护作用。方法采用微核试验、Ames试验和DNA修复试验方法评价不同浓度的枸杞糖粗品的抗突变作用。结果不同浓度的LBPc可使醋酸铅诱导的小鼠骨髓多染红细胞微核率明显降低，3个试验组的微核率分别为4．5‰、3．7‰、1．9‰，LBPc高剂量组（20mg/kg）与阳性对照组（5．3‰）相比，差异有非常显著性（P〈0．01），并呈剂量-反应关系；Ames试验结果表明，加入不同浓度的LBPc后，其抗突变作用由弱变强；职业人群服用LBPc1周后，其DNA修复速度明显提高（P〈0．01）。结论LBPe具有明显的抗突变活性。     

褪黑素对慢性间歇性缺氧性心肌cTnT及Ca2+-ATP酶的影响

褪黑素(melatonin,MLT)是由松果体分泌的一种重要的激素.作为动物体内普遍存在的MLT具有多种生物学活性,如:提高睡眠质量、增加机体免疫力、抗氧化作用等.本文阐述MLT生物学作用及其对慢性间歇性缺氧性损伤心肌cTnT及Ca2+-ATP酶的影响.     

5α-还原酶的分子生物学研究进展

综述类固醇5α-还原酶近年来的分子生物学进展.不仅已经发现5α-还原酶多种基因水平的缺陷与男性的外生殖器发育、前列腺疾病发生及生精功能密切相关,且发现其对女性生殖如分娩及多囊卵巢发生等也具有一定作用.另外,5α-还原酶可以调节皮肤中雄激素代谢情况从而影响痤疮、多毛症等发病.在中枢神经系统也具有重要的激素平衡调节功能,具有抗痫效应并且参与中枢性分化过程,甚至有人提出脑中存在第3种5α-还原酶.     

Keap1-Nrf2／ARE通路在分子毒理学中的研究进展

转录因子NF-E2相关因子2（N也）和它的胞质接头蛋白Keapl是细胞抗氧化反应的中枢调节者，Nrf2通过与抗氧化反应元件（ARE）相互作用，诱导编码抗氧化蛋白和Ⅱ相解毒酶的表达，在细胞的防御保护中发挥重要作用。Keapl—NrfR／ARE通路在抗肿瘤、抗应激、调节CSH合成、抗凋亡、抗炎症反应、神经保护等方面发挥着广泛的细胞保护功能。本文综述了Keapl-NrfR／ARE通路的最新研究，重点介绍其在分子毒理学中的研究进展。     

缺血缺氧致脑损伤的机制及牛磺酸的保护作用

缺血缺氧性脑损伤是临床上常见的疾患，其发病机制复杂。牛磺酸是细胞内的自由β-氨基酸，在大脑发育过程中具有神经营养因子和神经保护性因子作用。近年研究表明，牛磺酸在脑缺血缺氧中能拮抗兴奋性氨基酸的神经毒性、具有调节Ca^2 稳态的作用、减少一氧化氮(NO)和自由基产生、抗脂质过氧化、降低脑缺血中细胞凋亡的发生及影响缺氧诱导因子的表达，对脑缺血再灌注神经元损伤具有保护作用。     

高密度脂蛋白与动脉粥样硬化研究进展

大量研究表明高密度脂蛋白（HDL）具有胆固醇逆转运、抗氧化、保护血管内皮功能、抗血栓等抗动脉粥样硬化作用。但近年来的研究发现,在病理情况下HDL结构功能异常可能产生致动脉粥样硬化作用,而且在临床上应用某些升高HDL-C的药物并没有使患者心血管获益,提示调节HDL功能比升高HDL水平更重要。本文主要对高密度脂蛋白与动脉粥样硬化相关的研究进展进行综述。     

花生四烯酸CYP表氧化酶代谢产物EET对心肌病的保护作用

心肌病发病率有逐年升高的趋势,花生四烯酸及其表氧化酶代谢产物环氧二十碳三烯酸(EETs)在心肌疾病中具有重要的生理病理作用,如抗心肌缺血、抗炎症反应、改善内皮功能、抗血小板黏附与聚集等作用,可作用于多种心血管细胞的离子通道,也可调节凋亡相关基因和蛋白的表达,从而起到心肌保护作用。本文对EETs的产生途径以及对心肌的保护作用及机制加以阐述。     

Folate deficiency alters melatonin secretion in rats

The final step of melatonin (MLT) synthesis is methylation of N-acetyl-serotonin, with S-adenosylmethionine as a methyl donor provided by a metabolic pathway involving sulfur-containing amino acids (homocysteine and methionine). Remethylation of homocysteine to methionine requires folate. The present study was undertaken to test the influence of folate deficiency on MLT secretion. Severe folate deficiency was induced in rats by feeding them a synthetic diet containing (per kg diet) 0 mg folate and 10 g succinylsulfathiazole. Control rats were fed the same diet containing 8 mg folate/kg. After 4 wk, erythrocyte folate concentrations were significantly lower and plasma homocysteine levels were greater in folate-deficient rats than in controls. Pineal MLT concentration and urinary excretions of MLT, 6 sulfatoxymelatonin (the main hepatic MLT metabolite) and methoxylated catechol compounds were lower in the folate-deficient group than in the controls, whereas plasma catecholamine concentrations did not differ. Decreases generally were more marked at wk 2 than at wk 4 for the urinary metabolite excretions. These findings indicate that folate deficiency dramatically alters MLT secretion in rats.     

褪黑素对小鼠淋巴细胞电离辐射损伤的防护作用

目的 探讨褪黑素(MLT)对小鼠淋巴细胞电离辐射损伤的防护作用及其机制。方法 采用流式细胞术和荧光分光光度法在离体和整体条件下分别检测小鼠淋巴细胞凋亡小体百分率和DNA裂解率。在此基础上,腹腔注射MLT,观察2 Gy X射线全身照射后24 h小鼠胸腺、脾脏淋巴细胞数量及胸腺细胞³H-TdR掺入率和Con A、LPS诱导的脾T、B淋巴细胞转化率的变化。结果 离体研究中,小鼠胸腺和脾脏淋巴细胞体外接受0.5~6.0 Gy照射后,凋亡小体百分率、DNA裂解率均呈剂量依赖性增加,而照射前预先加入2 mmol/L MLT,细胞凋亡小体百分率、DNA裂解率与单纯照射组比较均显著降低。整体研究中,2Gy全身照射前腹腔注射MLT,小鼠胸腺和脾脏淋巴细胞凋亡小体百分率和DNA裂解率显著低于单纯照射组,接近或低于假照水平,MLT剂量在0.1~2.5 mg/kg范围内均有作用,但无明显剂量依赖性。小鼠胸腺、脾脏淋巴细胞数量、胸腺细胞³H-TdR掺入率及有丝分裂原诱导的脾脏T、B淋巴细胞转化率在2 Gy全身照射后均显著低于假照组(P <0.001)。0.5~10 mg/kgMLT预先腹腔注射,胸腺、脾脏淋巴细胞数显著高于0 mg/kg体重组(单纯照射),其中0.5 mg/kg体重组增高最显著;胸腺细胞³H-TdR掺入率显著增高(P <0.01或P <0.001),以0.5 mg/kg体重组增高最显著;Con A诱导的T细胞转化率显著增高,也以0.5 mg/kg体重组为著;LPS诱导的B细胞转化率增高,以10mg/kg体重组最显著。结论 MLT在体内和体外均可减轻电离辐射诱导的小鼠淋巴细胞损伤,对免疫功能具有保护作用。     

Melatonin induces changes to serum cytokines in mice infected with the Venezuelan equine encephalomyelitis virus

We determined the influence of melatonin (MLT) on the induction of interleukin (IL)-2, IL-1 beta, IL-4, tumour necrosis factor-alpha (TNF-alpha) and gamma interferon (IFN-gamma) on mice infected with the Venezuelan equine encephalomyelitis (VEE) virus. Levels of IFN-gamma in the MLT-treated group were significantly increased (P < 0.001) when compared with the control non-infected group from day 1 to 6 post-infection (p.i.), while in infected mice treated with 500 micrograms MLT/kg of bodyweight enhanced levels of IFN-gamma were evident from 4 to 6 days p.i. No differences were detected in the levels of IL-2 between the controls, the infected mice treated with MLT and the infected untreated group, from day 2 p.i. No changes in serum levels of IL-4 were detected. In infected mice treated with MLT, blood levels of IL-1 beta were elevated almost 10-fold from day 1 to day 6 p.i. when compared to the control, the infected and the non-infected MLT-treated mice (P < 0.001). A highly significant rise (P < 0.001) of TNF-alpha was found in infected mice treated with MLT, from day 1 to 6 p.i. when compared to the other groups. A significant rise (P < 0.001) was also evident in the infected non-MLT-treated group and a less pronounced rise in the non-infected mice treated with MLT when compared to controls. The blockade of IFN-gamma and TNF-alpha did not inhibit the protective effect of MLT but when IL-1 beta was neutralized, 100% of the infected mice died suggesting that IL-1 beta induced by MLT treatment is a target cytokine to generate an immune response against the viral infection.     

褪黑素和氨基胍对锰致大鼠肝脏毒性的影响

目的 研究褪黑素(MLT)和氨基胍(AG)对锰致大鼠肝毒性的影响,重点观察肝脏诱导型一氧化氮合酶(iNOS)活性和一氧化氮(NO)、丙二醛(MDA)含量的改变.方法 大鼠按体重随机分成4组,每组10只,第1组为对照组,第2组为单纯染锰组,第3、4组分别为MLT和AG干预组.第1和2组腹腔注射生理盐水,第3、4组分别腹腔注射MLT 5 mg/kg和AG 40 mg/kg;2 h后,第1组皮下注射生理盐水,第2、3、4组分别皮下注射MnCl2溶液200 μmol/kg,注射容量5 ml/kg.每周5次,共4周.4周后,测定血清乳酸脱氢酶(LDH)、丙氨酸氨基转移酶(GPT)以及肝脏一氧化氮合酶(NOS)活性和NO、MDA含量.结果 与对照组比较,单纯染锰组大鼠血清LDH和GPT的活性以及肝脏NO、MDA含量和iNOS活性明显升高,且差异有统计学意义(P<0.01);MLT干预组与单纯染锰组比较,血清LDH和GPT的活性以及肝脏NO、MDA含量和iNOS活性明显下降,且差异有统计学意义(P<0.01);AG干预组与单纯染锰组比较,血清LDH和GPT的活性以及肝脏NO含量和iNOS活性有所下降.结论 锰致肝损伤与肝细胞内iNOS活性升高和产生过多的NO和MDA有关,而且MLT和AG对锰的肝毒性有一定地保护作用.     

Impact of fish oil and melatonin on cachexia in patients with advanced gastrointestinal cancer: a randomized pilot study

OBJECTIVE: The effect of fish oil (FO), melatonin (MLT), or their combination and dietary advice on cachexia and biochemistry variables reflecting cachexia were investigated in patients with advanced gastrointestinal cancer. METHODS: Twenty-four patients not amenable to standard anticancer treatment and with documented weight loss and/or decreased serum albumin were included. They were randomized to 30 mL/d of FO, which provided 4.9 g of eicosapentaenoic acid and 3.2 g of docosahexanoic acid, or 18 mg/d of MLT for 4 wk. During the next 4 wk, all patients had FO and MLT. Serum or plasma was analyzed for tumor necrosis factor-alpha, interleukin-1beta, soluble interleukin-2 receptor, interleukin-6, and interleukin-8 and the fatty acids eicosapentaenoic acid, docosahexanoic acid, arachidonic acid, and linoleic acid. RESULTS: Serum levels of eicosapentaenoic acid and docosahexanoic acid increased as expected with FO. No major changes in biochemical variables and cytokines were observed with any intervention. In the FO group, 5 of 13 patients (38%) showed weight stabilization or gain compared with 3 of 11 patients (27%) in the MLT group. After combining interventions, approximately 63% of patients showed such responses. CONCLUSIONS: FO, MLT, or their combination did not induce major biochemical changes indicative of a strong anticachectic effect. Nonetheless, the interventions used may have produced a weight-stabilizing effect.     

Melatonin prolongs survival of immunodepressed mice infected with the Venezuelan equine encephalomyelitis virus

Male albino mice immunodepressed after the injection of dexamethasone (DEX) were inoculated intraperitoneally with the Guajira strain of Venezuelan equine encephalomyelitis (VEE) virus. Melatonin (MLT) was administered daily, at a dose of 500 micrograms/kg bodyweight, for 3 days before virus inoculation and 10 days after. Serum levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) were determined in all the experimental groups (control, DEX, DEX + MLT, DEX + VEE, DEX + VEE + MLT, VEE and MLT). At day 6 after the virus inoculation, the survival rate was significantly increased from 0% in group DEX + VEE to 32.5% in the group of immunodepressed infected mice treated with MLT (DEX + VEE + MLT). By day 10 a survival rate of 10% was found in group DEX + VEE + MLT and 0% in group VEE. No alterations in IL-2 serum levels were observed. MLT increased GM-CSF in control and in DEX-treated mice. In the VEE virus-infected mice treated with DEX, serum levels of GM-CSF increased progressively from day 1 to 5 postinoculation. In contrast, the levels of GM-CSF in infected immunodepressed mice treated with MLT decreased significantly from day 1 to 5 postinoculation. At day 5 after viral inoculation, no differences were detected in the cerebral viral titres in groups VEE, DEX + VEE and DEX + MLT + VEE. These results show that MLT does not inhibit VEE viral replication in the brain of immunodepressed mice.     

Analysis of melatonin in foods

Melatonin (N-acetyl-5-methoxytriptamine), a neurohormone produced by the pineal gland, has recently been reported in foods, mainly of plant origin. Literature concerning the biological properties is extensive. However, little is known about melatonin presence in foods or the analytical methods suitable for assay in food matrices and the potential influence of dietetic intake on human health. The aim of this work is to review current knowledge and available data of dietary intake of melatonin as it has been proposed as a new bioactive food component. There are gaps in the knowledge and insufficiently standardised methods for its analysis. Advantages and disadvantages of analytical methods to assess melatonin in different food matrixes are discussed, as well as the effect of dietetic melatonin.     

Melatonin – Schlüssel für die Bewertung der Wirkung elektrischer und magnetischer Felder?

The human pineal gland produces melatonin in a circadian rhythm. The substance has different functions – as a hormone, as an antioxidant and as a neurotransmitter. The secretion of melatonin and its tumor inhibition function can be influenced by electric and magnetic fields. Investigations have been caried out with rodents which have a melatonin rhythm similar to humans; nevertheless, they show a high variability between the species. The present state of knowledge only allows limited use of melatonin as an indicator for the impact of electric and magnetic fields.     

Prenatal melatonin and its interaction with tachykinins in the hypothalamic-pituitary-gonadal axis

The pineal gland, through its hormone melatonin, influences the function of the hypothalamic-pituitary-gonadal axis. Tachykinins are bioactive peptides whose presence has been demonstrated in the pineal gland, hypothalamus, anterior pituitary gland and the gonads, in addition to other central and peripheral structures. Tachykinins have been demonstrated to influence the function of the hypothalamic-pituitary-gonadal axis, acting as paracrine factors at each of these levels. In the present review, we examine the available evidence supporting a role for melatonin in the regulation of reproductive functions, the possible role of tachykinins in pineal function and the possible interactions between melatonin and tachykinins in the hypothalamic-pituitary-gonadal axis. Evidence is presented showing that melatonin, given to pregnant rats, influences the developmental pattern of tachykinins in the hypothalamus and the anterior pituitary gland of the offspring during postnatal life. In the gonads, the effects of melatonin on the tachykinin developmental pattern were rather modest. In particular, in the present review, we have included a summary of our own work performed in the past few years on the effect of melatonin on tachykinin levels in the hypothalamic-pituitary-gonadal axis.