褪黑素与绵羊的季节性生殖

绵羊是一种短光照型生殖动物,具有明显的生殖季节性。人们普遍认为,绵羊生殖周期与环境光周期的同步变化是通过褪黑素作用于下丘脑－垂体－性腺轴系统来实现的。近年来的不少研究结果表明,绵羊对光周期的感受性还受褪黑素受体的调控。现从生态学（光周期的生殖效应）、神经内分泌学和分子生物学（褪黑素受体）等领域的研究进展出发,对褪黑素调控绵羊自然季节性生殖的作用及机制进行系统综述。     

褪黑素调控动物繁殖功能的作用途径

褪黑素是由松果体分泌的一种多功能吲哚类激素,在动物繁殖过程中起了至关重要的作用.褪黑素可通过多条途径调控动物的繁殖功能,主要包括：G蛋白偶联受体途径;作为神经内分泌激素对动物繁殖进行调控;与其核受体结合在转录水平上调控动物繁殖;通过抗氧化作用调控卵泡发育.本文就褪黑素对动物繁殖功能的调控途径进行综述,旨在为褪黑素调控动物繁殖的相关研究提供帮助.     

褪黑素激活大鼠大脑中动脉BKCa通道的受体依赖和非受体依赖途径

目的：研究褪黑素通过大电导Ca²⁺激活K⁺（BK_Ca）通道介导大脑中动脉张力变化的作用机制。方法：8周龄雄性Wistar大鼠,麻醉后取大脑中动脉,酶消化法急性分离脑中动脉平滑肌细胞,采用膜片钳技术全细胞记录模式检测细胞外液加入褪黑素前后BK_Ca通道和电压门控钾（K_V）通道的电流密度,褪黑素受体抑制剂2-苯基-N-乙酰色胺（luzindole）孵育后,全细胞记录模式记录加入褪黑素后BK_Ca通道电流幅值和贴附式单通道记录模式记录加入褪黑素后BK_Ca通道Po值,内面向外记录模式检测加入褪黑素后BK_Ca通道电导（G）,开放概率（Po）,平均开放时间（To）和关闭时间（Tc）。结果：①褪黑素（100 μmol/L）显著增加全细胞BK_Ca通道电流密度,但对K_V通道电流密度无显著影响;②luzindole （1 μmol/L）显著抑制褪黑素引起的BK_Ca通道电流密度增加;③贴附式单通道记录模式下,褪黑素（100 μmol/L）增加BK_Ca单通道Po值,luzindole （1 μmol/L）显著抑制褪黑素引起的Po增加;④内面向外单通道记录模式下,褪黑素（1 μmol/L,100 μmol/L）缩短BK_Ca单通道的To和Tc值,且Tc较To显著缩短;结论：褪黑素通过受体依赖和非受体依赖途径激活BK_Ca通道,介导大脑中动脉血管舒张。     

褪黑素和褪黑素受体对下丘脑-垂体-肾上腺轴作用的研究进展

松果体于儿童中期可发育至最高峰,普遍在7岁之后开始呈逐渐萎缩,并在成年后逐渐有钙盐沉着。褪黑素主要是由松果体进行合成和分泌所形成,存在较好的昼夜节律性,且通常是通过下丘脑的视交叉上核进行控制,并与环境中的光-暗呈现的周期改变存在密切关联。此外,褪黑素具有极其广泛的生物学作用,且其发挥作用的首站便是与特异性褪黑素受体相关结合,随后经由信号转导系统发挥相应的生物效应。褪黑素受体属于G蛋白耦联受体超家族重要成员之一,其主要是通过百日咳毒素敏感G蛋白的一致性G蛋白通路,减少环腺苷酸的急剧或(和)抑制毛喉菇素刺激的环腺苷酸升高,从而间接影响黑色素活动。下丘脑-垂体-肾上腺轴(HPA轴)是机体在发生应激反应过程中具有一定影响的系统,其所分泌的激素也会表现出昼夜节律性的改变,且此种改变与褪黑素的有关变化呈现出明显的相反性。提示了两者可能存在一定的相关,在机体免疫功能的调控中扮演着不同的角色。本文通过阐述褪黑素和褪黑素受体对HPA轴作用的最新研究进展,旨在明确三者存在的错综复杂的相互作用关系,继而为机体免疫功能调控的一系列疾病研究提供参考依据。     

褪黑素受体与GABAA受体在褪黑素延长小鼠睡眠时间中的作用

目的：研究褪黑素受体和GABAA受体在褪黑素延长小鼠睡眠时间中的作用。方法：以翻正反射消失为睡眠开始的指标,至翻正反射恢复作为睡眠时间。观察不同受体激动剂或拮抗剂对褪黑素催眠作用的影响。结果：褪黑素3型受体拮抗剂盐酸哌唑嗪对褪黑素延长小鼠睡眠时间的作用无明显影响。GABA受体内源性激动剂GABA能明显增强褪黑素延长小鼠睡眠时间的作用,而GABAA受体上的印防己毒素结合位点的配基,即氯离子通道阻断剂印防己毒素能明显拮抗褪黑素的催眠作用,GABAA受体上的GABA结合位点的拮抗剂荷包牡丹碱则对褪黑素延长小鼠睡眠作用无明显影响。结论：褪黑素延长小鼠睡眠时间的作用与褪黑素3型受体无关,而与GABAA受体关系密切,其作用主要由印防己毒素结合位点介导。     

褪黑素受体激动剂改善高糖高脂喂养大鼠脂联素敏感性

目的观察褪黑素受体激动剂（NEU-P11）对高糖高脂饲养大鼠脂联素敏感性的影响。方法将30只SD大鼠随机分为对照组（CD组）,高糖高脂组（HFSD组）,褪黑素组（Mel组）,褪黑素受体激动剂组（NEU-P11组）。CD组饲以正常饲料;其余3组饲以高糖高脂饲料。6个月后,给药治疗2个月。治疗期间,Mel组每天注射Mel（4mg／kg）;NEU—P11组每天注射NEU-P11（10mg／kg）;CD组以及HFSD组注射生理盐水（5ml／kg）。测定糖脂代谢指标并做口服葡萄糖耐量实验（oral glucose tolerant test,OG-TY）,Western印迹检测脂联素（adiponectin,APN）在脂肪组织及脂联素受体（AdipoR）在骨骼肌组织中的表达变化。结果高糖高脂饮食可诱导SD大鼠产生胰岛素抵抗,脂联素表达增加。Neu-P11治疗后,胰岛素敏感性增强．脂联素表达降低至正常水平。结论Neu-P11能提高胰岛素敏感性,改善脂联素抵抗。     

肾上腺素对幼龄小鼠胸腺褪黑素受体的调节

应用放射配体结合法检测幼龄小鼠胸腺褪黑素受体（ＭＲ）,并以此为实验模型研究肾上腺素（Ｅ）对胸ＭＲ的影响及作用机制。结果表明,生理浓度的Ｅ即对胸ＭＲ有明显抑制作用,其抑制效应具时间依赖性及剂量依赖性。β－肾上腺素能受体拮抗剂普萘洛尔可逆转引抑制效应,ＣＡＭＰ对ＭＲ也有明显抑制作用,表现Ｅ对ＭＲ的抑制是通过β受体而实现的。这些结果提示,Ｅ在生理情况下即对胸腺ＭＲ有调节作用。     

普洱大叶茶中对褪黑素受体具有激动作用的活性化合物

对普洱大叶茶中具有褪黑素受体激动作用的活性化合物进行了跟踪分离和活性测试。在活性跟踪指导下,综合运用硅胶柱层析和高效液相色谱等分离技术,从普洱大叶茶新鲜叶片中发现9个活性化合物,分别被鉴定为(+)-7′,7′-dimethyl-5-hydroxy-2R,3S-trans-pubeschin(1)、plumbocatechin A(2)、(-)-儿茶素(3)、儿茶素-3-氧-没食子酸酯(4)、没食子儿茶素没食子酸酯(5)、表没食子酸儿茶素没食子酸酯(6)、(-)-表儿茶素(7)、没食子酸儿茶素(8)和表没食子酸儿茶素(9),其中,化合物1、2为首次从山茶属中分离得到。MTT法测试表明化合物1～9对褪黑素受体均具有一定的激动作用,化合物3很有可能是茶叶调节MT受体而发挥抗精神疾病活性的主要成分。     

褪黑素受体及其介导的抗肿瘤机制研究进展

褪黑素(melatonin,MT)是由松果腺分泌的一类神经内分泌激素,具有维持生理节奏、增强免疫调节、抗氧化、保护唾液腺、增强肌肉力量等生理功能。有研究发现,褪黑素可通过与其受体结合发挥抗肿瘤作用,关于这方面的研究已成为当今热点领域。该文就褪黑素抗肿瘤机制及其受体作用的研究进展作一阐述,通过总结有关褪黑素研究现状并进行展望,为褪黑素临床合理、精准用药提供理论基础。     

褪黑素调节卵巢功能及相关机制的研究进展

褪黑素是一种神经内分泌激素,在动物体内主要由松果体合成和分泌,具有调节昼夜节律的重要作用,包括卵巢生物钟系统。褪黑素在外周组织器官如女性生殖器官卵巢中也发挥重要生理作用。女性生殖过程中,卵泡不断产生并累积活性氧,进而造成组织细胞损伤。褪黑素可通过受体依赖或者受体非依赖的机制参与卵巢功能调节。最近研究发现,褪黑素还可通过调节细胞自噬机制发挥效应。该文就褪黑素对卵巢的保护作用及其相关机制的研究进展进行综述。     

褪黑激素受体基因的研究进展

褪黑激素通过与药理学特异性的高亲和性G-蛋白耦联受体相结合来发挥其生物学功能。本文介绍了褪黑激素受体的结构、功能与调控、褪黑激素受体基因的克隆及基因结构、褪黑激素受体基因的发育性表达与作用、褪黑激素受体基因的定位与多态性分析,并讨论了该基因与繁殖季节性的关系。 Abstract:Melatonin exerts its biological effects through pharmacological specific,high affinity G protein-coupled receptors.This review introduced the structure,function,and regulation of melatonin receptor,the cloning and structure,developmental expression,mapping and polymorphism of melatonin receptor gene.The relationship between melatonin receptor gene and reproductive seasonality was also discussed.     

Dexamethasone modulates melatonin MT2 receptor expression in splenic tissue and humoral immune response in mice

Melatonin modulates immune function through its membrane-bound MT1 and MT2 receptors in mammalian system. Adrenal glucocorticoid, an important metabolic hormone is known as a immuno-compromising agent. In the present study, we investigated the effect of dexamethasone on melatonin receptor proteins in spleen tissue and anti-klh-IgG response in Swiss albino mice. Melatonin treatment increased the MT1 and MT2 receptor proteins and anti-klh-IgG than control mice. Dexamethasone treatment increased MT2 receptor protein and anti-klh-IgG than melatonin-treated group. Dexamethasone treatment to melatonin-treated mice showed additive effects and maximally increased the anti-klh-IgG than other experimental groups. A decrease in glucocorticoid receptor (GR) protein was noted in melatonin treated as well as dexamethasone-treated mice. Dexamethasone significantly increased MT2 melatonin receptor protein in spleen and anti-klh-IgG and additively increased anti-klh-IgG when supplemented along with melatonin. Therefore, the present study may suggest that dexamethasone increased humoral immune response permissively by enhancing MT2 receptor expression in splenic tissue of mice.     

褪黑激素的研究进展

褪黑激素是一种在多个物种的多个组织中广泛存在并具有重要生理作用的激素。本文拟就褪黑激素在体内的分布,褪黑激素受体的分子结构、药理学特性、生物功能及调控模式作一简述。     

In vivo activation of insulin receptor tyrosine kinase by melatonin in the rat hypothalamus

Melatonin is the pineal hormone that acts via a pertussis toxin-sensitive G-protein to inhibit adenylate cyclase. However, the intracellular signalling effects of melatonin are not completely understood. Melatonin receptors are mainly present in the suprachiasmatic nucleus (SCN) and pars tuberalis of both humans and rats. The SCN directly controls, amongst other mechanisms, the circadian rhythm of plasma glucose concentration. In this study, using immunoprecipitation and immunoblotting, we show that melatonin induces rapid tyrosine phosphorylation and activation of the insulin receptor beta-subunit tyrosine kinase (IR) in the rat hypothalamic suprachiasmatic region. Upon IR activation, tyrosine phosphorylation of IRS-1 was detected. In addition, melatonin induced IRS-1/PI3-kinase and IRS-1/SHP-2 associations and downstream AKT serine phosphorylation and MAPK (mitogen-activated protein kinase) phosphorylation, respectively. These results not only indicate a new signal transduction pathway for melatonin, but also a potential cross-talk between melatonin and insulin.     

Melatonin attenuated mediators of neuroinflammation and alpha-7 nicotinic acetylcholine receptor mRNA expression in lipopolysaccharide (LPS) stimulated rat astrocytoma cells,C6

Abstract

Melatonin has been known to affect a variety of astrocytes functions in many neurological disorders but its mechanism of action on neuroinflammatory cascade and alpha-7 nicotinic acetylcholine receptor (α7-nAChR) expression are still not properly understood. Present study demonstrated that treatment of C6 cells with melatonin for 24 hours significantly decreased lipopolysaccharide (LPS) induced nitrative and oxidative stress, expressions of cyclooxigenase-2 (COX-2), inducible nitric-oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP). Melatonin also modulated LPS-induced mRNA expressions of α7-nAChR and inflammatory cytokine genes. Furthermore, melatonin reversed LPS-induced changes in C/EBP homologous protein 10 (CHOP), microsomal prostaglandin E synthase-1(mPGES-1) and phosphorylated p38 mitogen activated protein kinase (P-p38). Treatment with pyrrolidine dithiocarbamate (PDTC) inhibited α7-nAChR mRNA expression in LPS-induced C6 cells. Our findings explored anti-neuroinflammatory action of melatonin, which may suggests its beneficial roles in the neuroinflammation associated disorders.     

Melatonin,a toll-like receptor inhibitor: Current status and future perspectives

Toll-like receptors (TLRs) are crucial activators of inflammatory responses, they are considered immune receptors. TLRs are of fundamental importance in the pathophysiology of disorders related to inflammation including neurodegenerative diseases and cancer. Melatonin is a beneficial agent in the treatment of inflammatory and immune disorders. Melatonin is potent anti-inflammatory hormone that regulates various molecular pathways. Withal, limited studies have evaluated the inhibitory role of melatonin on TLRs. This review summarizes the current knowledge related to the effects of melatonin on TLRs in some common inflammatory and immunity disorders.     

Minireview: Versatile Melatonin: A Pervasive Molecule Serves Various Functions in Signaling and Protection

Melatonin, which is able to enter all tissues and all compartments of the cell, acts in a highly pleiotropic fashion. Some melatonin effects are mediated by membrane receptors, others are receptor independent. Melatonin is produced in the pineal gland and various extrapineal organs of vertebrates, but is also found in invertebrates, angiosperms, and unicells. In mammals, melatonin elicits various secondary humoral responses, e.g., in the immune system via interleukin-4 and other cytokines and in the brain by modulation of NO formation. Melatonin is also a powerful radical scavenger, terminating free radical reaction chains initiated by photooxidants, hydroxyl or peroxyl radicals. The protective potency of this indoleamine is demonstrated by various experiments.