褪黑素与血压昼夜节律的相关性研究

目的通过比较血压昼夜节律异常和正常者的白昼和黑夜的尿中褪黑素的代谢产物6．羟基硫酸褪黑素（6-SMT）的变化，以研究褪黑素与血压昼夜节律的关系。方法对入选者进行24h动态血压监测，测定昼夜血压。用ELISA法测定患者白昼和黑夜尿6-SMT含量，并计算黑夜／白昼尿6-SMT比值。结果各组患者的黑夜尿6-SMT量高于白昼（P〈0．01）。非杓型高血压组的黑夜尿6-SMT量和黑夜／白昼尿6-SMT比值低于杓型高血压组和对照组（P〈0．01）。在各组内，各黑夜／白昼尿6-SMT比值与其组夜间血压下降率均存在正相关（P〈0．05）。结论褪黑素在人体存在昼低夜高的生理节律，血压节律呈现杓型分布的杓型高血压组和对照组，其褪黑素在黑夜分泌较多。而在非杓型高血压组褪黑素黑夜分泌明显减少，与血压昼夜节律异常存在密切关系。褪黑素的黑夜分泌量与夜间血压下降程度相关，其节律性分泌与血压昼夜节律密切相关。     

褪黑激素与脑保护

褪黑激素是一种神经内分泌激素,具抗氧化、抗兴奋毒性、抗凋亡、改变胞内外信号转导、改变膜通道通透性等作用,在脑缺血性损伤、神经退行性变、癫痫等的防治方面显示出良好的治疗前景。本文就MT对脑的保护作用进行综述。     

褪黑素对大鼠肠缺血/再灌注损伤保护作用的实验研究

目的:观察褪黑素对大鼠肠缺血/再灌注损伤的保护作用。方法:成年雄性SD大鼠60只分为假手术组(10只)、缺血/再灌注组(10只)、缺血/再灌注+褪黑素20mg/kg组(15只)。观察肠缺血30min再灌注60min后肠黏膜损伤程度,测定血中D乳酸和内毒素水平,并测定小肠组织中丙二醛(MDA)、一氧化氮(NO)水平和诱生型-氧化氮合酶(iNOS)活力。结果:运用褪黑素组肠黏膜损伤程度轻,MDA、NO、iNOS和D乳酸、内毒素均低于缺血/再灌注组和溶媒组,并呈剂量依赖效应。肠黏膜损伤程度与MDA、NO及D乳酸呈正相关。结论:运用褪黑素对大鼠肠缺血/再灌注损伤有保护作用,效应呈剂量依赖性。这种作用的部分原因可能是褪黑素抑制了NO的过度生成。     

Serotonin, excitatory amino acids and the photic control of melatonin rhythms and SCN c-FOS in the rat

There is a growing acceptance that serotonergic pathways to the suprachiasmatic nucleus play an important role in the mediation and modulation of light entrainment of rhythms. In this study administration of the 5-HT(2A/2C) agonist (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI, 0.5 mg/kg) at mid dark caused a phase shift in the onset of the urinary excretion of 6-sulphatoxymelatonin in rats that was sustained for at least 8 days and was blocked by the specific 5-HT(2C) antagonist SB-242084. Administration of DOI (2 mg/kg) across the night resulted in the appearance of c-FOS in the nucleus of cells in the suprachiasmatic nucleus during subjective darkness, but did not cause induction at the time of expected lights on (CT0). By contrast light exposure induced c-fos throughout the night including CT0. Administration of the NMDA receptor antagonist MK-801 (3 mg/kg) prior to light pulses had no effect on c-fos in the first part of the night, but towards the expected time of lights on, became progressively more potent, such that by CT0, light induction of c-fos was almost completely inhibited. These results provide further evidence that serotonin plays a role in the mediation of light effects on rhythms in the rat.     

褪黑素联合缬沙坦治疗2型糖尿病早期肾病

目的：观察褪黑素与缬沙坦联合治疗2型糖尿病早期肾病的临床疗效。方法：选择2型糖尿病早期肾病患者60例，均维持原有抗糖尿病药物控制高血糖，饮食、活动量不变，将患者随机分为两组，常规治疗组应用缬沙坦80mg/d，联合治疗组用缬沙坦80mg/d，同时加用褪黑素10mg/d。应用6个月后观察两组患者肾功能及24h尿微量白蛋白的变化。结果：6个月后，两组患者24h尿微量白蛋白均有降低，联合治疗组较单缬沙坦治疗组24h尿白蛋白降低更明显，两组比较差异显著（P〈0.05）。结论：褪黑素与撷沙坦联合治疗2型糖尿病早期肾病安全、有效，可以更好地降低24h尿微量白蛋白，延缓糖尿病早期肾病的进程。     

Radioligand binding affinity and biological activity of the enantiomers of a chiral melatonin analogue

Melatonin, a hormone secreted by the pineal gland, can act on the central circadian oscillator in the suprachiasmatic nucleus of the hypothalamus. It has been proposed that melatonin or its analogues may be useful in restoring disturbed circadian rhythms in jet-lag, shift-work and some blind subjects, and as sleep-promoting agents. In the present study, the (−)- and (+)-enantiomers of N-acetyl-4-aminomethyl-6-methoxy-9-methyl-1,2,3,4-tetrahydrocarbazole (AMMTC) were separated and tested. The affinity of the enantiomers at the specific 2-[¹²⁵I]iodomelatonin binding site in chick brain membranes was compared in competition assays, and their biological activity in a specific melatonin receptor bioassay, aggregation of pigment granules in Xenopus laevis melanophores. The (−)-enantiomer of AMMTC was 130-fold and 230-fold more potent than the (+)-enantiomer in competition radioligand binding assays and melanophores, respectively. Both enantiomers are melatonin receptor agonists; (−)-AMMTC is slightly more potent than melatonin itself. As the tetrahydrocarbazole nucleus holds the C-3 amido side-chain of AMMTC in a restricted conformation, the analogues will be useful in modelling the melatonin receptor binding site.     

褪黑素与男性生殖

褪黑素 (MLT)是一种主要由松果体分泌的神经内分泌激素 ,在生物体内具有广泛的生理作用。作者对MLT在男性生殖中的作用及在男科临床中的应用进行综述     

高效液相色谱法快速测定进口保健食品中褪黑激素的方法研究

研究了进口保健食品中褪黑激素的提取、净化、定性、定量的高效液相色谱(HPLC)法条件，建立了HPLC法快速测定保健食品中褪黑激素的可靠方法。本方法具有操作简便、快速、结果准确可靠、再现性好的特点。褪黑激素在两种进口保健食品麦乐通中三个水平的添加回收率在97．6％～105．7％之间，变异系数(n=8)在0．27％～1．64％之间，该方法在0．01mg／ml～0．2mg／ml浓度范围内有良好的线性关系，相关系数r=0．9998；最低检出浓度1.1μg／ml；最小检出量2．8ng。     

Low dose melatonin improves sleep in healthy middle-aged subjects

We studied the effects of single evening doses of melatonin (0.3 mg and 1.0 mg orally) on polysomnographically measured sleep in 15 healthy middle-aged volunteers, using a placebo-controlled, double-blind, cross-over design. Compared to placebo, the 1.0 mg dose of melatonin significantly increased Actual Sleep Time, Sleep Efficiency, non-REM Sleep and REM Sleep Latency. These data are consistent with the hypothesis that low dose melatonin has hypnotic effects in humans. It is possible that administered melatonin may have a role to play in the treatment of sleep disorders.     

Influence of cigarette smoking on melatonin levels in man

Objective Polycyclic aromatic hydrocarbons in cigarette smoke induce cytochrome P₄₅₀(CYP)1A2, which is involved in the hepatic metabolism of melatonin (MT). This suggests that habitual smokers may have low serum MT levels during smoking compared with a non-smoking period. We decided to investigate whether this suggestion is correct.Methods Eight habitual smokers were tested on two occasions. They had smoked prior to the first occasion but had not smoked for 7 days prior to the second. Each test was divided into two parts. The first part spanned the night between 2000 hours and 0800 hours. Venous blood samples were collected every second hour during this period for analysis of endogenous serum MT. The second part was performed the subsequent day. At 0930 hours, 25 mg MT was ingested orally, and blood samples for exogenous serum MT analysis were collected every hour between 1000 hours and 1600 hours. Endogenous and exogenous areas under the serum MT–time curve (MT-AUCs) were calculated.Results Endogenous serum MT-AUCs were similar during the two periods. Oral administration of MT induced supraphysiological levels of serum MT. Moreover, exogenous serum MT-AUCs were significantly smaller before than after smoking abstinence (7.34±1.85 versus 21.07±7.28 nmol/l×h; P<0.02; means±SEM).Conclusion This investigation shows that exogenous, but not endogenous (at night), serum MT levels are influenced by cigarette smoking. When the MT levels are low, the influence of CYP1A2 levels appears to be less pronounced than when they are high, and the enzyme capacity hugely utilized. These findings implicate that interactions between exogenous MT, and substrates metabolized by CYP1A2, may differ in individuals before and after smoking abstinence.