松果腺及褪黑素与衰老

衰老是机体随年龄的增长逐渐丧失对环境的适应能力。这个过程伴有行为、内分泌及其他生理功能的改变，使得机体抵抗损伤性刺激的能力降低，对疾病的易感性增加。松果腺的功能随年龄的增加而变化，并与衰老的进程平行。年龄增加松果腺钙化率增高，其生物合成和分泌功能降低，松果腺移植可延缓动物的衰老。褪黑素是吲哚类物质，主要来源于松果腺细胞，血中水平与年龄有关，衰老可导致褪黑素水平下降。外源性褪黑素能延长大鼠的生存期，并能推迟家兔老年性疾病的发生时间。进一步研究发现松果腺和褪黑素延缓衰老与其具有抗自由基作用，调节炎症免疫反应，调节生物钟，影响激素分泌和参与应激等功能有关。而老年期体内自由基清除能力降低、激素分泌紊乱、生物钟衰退、肿瘤及其他疾病的易感性增加正是衰老的重要特征。因此，对褪黑素的深入研究将为抗衰老药的开发开辟新的途径     

抗衰老药物的研究进展

近年来关于衰老的研究以及根据衰老的机制寻找高效的抗衰老药物的研究已成为当前医药学研究领域中的热点问题,并已在很多方面取得了长足的进展。本文就近年来衰老及抗衰老药物的研究进展综述如下:(1)衰老的研究:衰老是机体各组织、器官功能随年龄增长而发生的退行性变化,是机体各种生化反应的综合表现,是体内外许多因素共同作用的结果。近半个多世纪以来,国际上已经提出一系列衰老学说,为揭开衰老机制及开发抗衰老药物奠定了基础。包括自由基学说、线粒体DNA损伤学说、衰老的端区学说、免疫学说(immunolog-ical theory)、内分泌学说(endocrine theory)等。(2)抗衰老药物是一类以提高生命效率(生存时间与生命活力的总和)为最终目的的药物,从多系统、多层次和多阶段来发挥其调整功能,它能在遗传学上所界定的寿限内延迟衰老或提高生命质量。抗衰老药物按理化属性可分为:①化学药物,有抗氧化剂、抗衰老激素、营养素、单胺氧化酶抑制剂、免疫调节剂、生化制剂、大脑功能促进药等。②中药,有单味中药以及复方制剂。虽然目前有很多药物研究都证明能够延缓衰老,作用安全,但抗衰老药物不可乱用,其应用既要符合综合性、早期性和长期性原则,又要从个体的实际出发,因人制宜地选用抗衰老药物。     

褪黑素抗氧化作用研究进展

褪黑素（MT）由松果腺分泌,具有明显的生物节律性,包括昼夜节律、季节节律和生命周期节律。MT分泌减少与机体衰老关系密切,有松果体钙化、生物钟、神经内分泌-免疫系统及自由基损伤等多种学说,尤其神经系统退变与自由基累积性损伤密切相关。MT是一强大的内源性自由基清除剂,可以对抗羟自由基对机体的攻击以及谷氨酸兴奋毒性作用,对中枢神经系统有保护作用。体内研究证明,遏制老化期MT的下降,保护MT生成的内源性节律或外源性使用MT能够明显地延长寿命,减少老年相关性疾病的发生。MT抗衰老研究具有广阔前景。     

生物节律、松果腺与衰老

本文主要阐述了生物节律、松果腺(褪黑素)与衰老三者的关系。     

褪黑素对D-半乳糖衰老模型小鼠的作用

目的　研究褪黑素 (melatonin ;MT)对D 半乳糖所致小鼠各项衰老指标的对抗作用 ,以期探讨MT的抗衰老作用机制。方法　D 半乳糖衰老模型小鼠为实验对象 ,以其体重、免疫器官重量 ,肝、脑丙二醛 (malondialdehyde ;MDA)和脂褐素的含量 ,全血谷胱甘肽过氧化物酶 (glutothineper oxidase;GSH Px)、红细胞过氧化氢酶 (catalase;CAT)和脑中超氧化物歧化酶 (superoxidedismutase;SOD)的活力 ,脑中谷氨酸水平以及骨髓多染红细胞微核形成为指标 ,全面考察MT的抗衰老作用。结果　MT(0 5、1 0mg·kg-1,ip)能对抗连续 6周给D 半乳糖 (15 0mg·kg-1,sc)所致小鼠肝、脑组织MDA、脂褐素含量的增加和骨髓细胞微核的形成 ,明显抑制脑中谷氨酸含量的升高 ,提高全血GSH Px、红细胞CAT和脑中SOD的活力 ,并阻抗小鼠体重及胸腺指数下降。结论　MT能有效地防止D 半乳糖所致的小鼠多项衰老体征的出现 ,改善小鼠的机能状态。对衰老的松果腺学说提供有力的支持     

松果腺抗辐射损伤作用的研究

目的主要研究电离辐射对松果腺细胞分泌褪黑素的影响以及松果腺在抗辐射损伤中的作用。方法采用高压液相色谱分析法检测松果腺细胞中褪黑素的变化，采用常规记数法测定外周血细胞数。结果(1)小鼠受1～6GyX射线全身照射后12h，随剂量增加松果腺细胞中褪黑素含量逐渐降低。(2)小鼠6GyX射线全身照射后72h，去松果腺组外周血细数明显下降，小鼠受6GyX射线全身照射后14d去松果腺组死亡率增高。结论松果腺及其分泌的褪黑素有对抗辐射损伤的作用。     

人类的衰老与抗衰老

人类的衰老是一个慢性复杂的过程，是许多因素共同作用的结果。由衰老所致的机体功能下降或疾病不仪是可以预防的，在某种程度上也是可以逆转的。二十世纪的生命科学研究将人类对衰老的认识从整体动物水平推进到了细胞水．甲和分子水平，最终归结为两大类型：一类为遗传衰老学说，另一类为环境伤害衰老学说。两大类型的衰老研究各有建树，但也各有不足。本文对目前最有影响的衰老学说作一些重点分析比较，进而对新世纪的衰老与抗衰老研究做出瞻望。     

松果腺褪黑素与炎症免疫调节

松果腺褪黑素与炎症免疫调节丁长海，魏伟，徐叔云（安徽医科大学临床药理研究所，合肥２３００３２）自１９５８年Ｄｅｒｎｅｒ从牛的松果腺分离提纯出褪黑素（ｍｅｌａｔｏｎｉｎ，ＭＴ）以来，松果腺的功能逐渐被人们认识。它位于中脑上丘之上，第三脑室后端，实质由松...     

延衰驻颜之本

数千年来，人类一直都在探索着衰老之因。现代科学家认为，衰老的原因至今还没完全清楚，公认的有两大因素：一是先天因素，即基因程序因素，由基因控制衰老的进行；二是后天因素，即内外环境（包括物理、化学、生物和机械因子）造成的损伤，导致机体功能的减退或丧失而出现衰老，并提出了几种衰老学说：蛋白质更替相关学说、自由基学说、器官系统理论、衰老的免疫学说等。     

褪黑素的抗肿瘤作用机制和化疗增敏作用研究现状

褪黑素(MLT)是由松果腺合成与分泌的神经内分泌活性物质,其以色氨酸为原料,经过羟化、脱羧及N-乙酰转移酶等的催化后而最终形成.MLT可迅速进入血液循环,分布到全身各部位发挥生理活性.现已证实,MLT除了可保证正常生物节律、调节内分泌腺的功能、抗应激和延缓衰老外,与肿瘤的发生、发展及治疗亦有着密切的关系[1].     

Involvement of melatonin MT(3) receptors in the regulation of intraocular pressure in rabbits

Melatonin, a neurohormone secreted by the pineal gland, can stimulate three subtypes of receptors, namely: mt(1), MT(2) and MT(3). We examined the ability of melatonin and the selective MT(3) receptor agonist, 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT), to modify intraocular pressure in rabbits. Both compounds significantly reduced intraocular pressure, maximally by 24% and 43%, respectively, with IC(50) values of 363+/-23.0 and 423+/-30.0 ng/10 microl (1.6+/-0.1 and 1.8+/-0.1 nmol, respectively). The non-specific melatonin receptor antagonist, luzindole, abolished the depressant effect of both compounds, thus confirming the involvement of melatonin receptors. Our results show, for the first time, a functional response that may be regulated by melatonin MT(3) receptors, and provide evidence that supports a role of melatonin in the circadian changes of intraocular pressure.     

褪黑素与多囊卵巢综合征关系的研究现状

褪黑素(MT)是松果体分泌的神经内分泌激素,除了参与调节昼夜节律,在女性生殖、免疫以及抗氧化等方面也发挥着十分重要的作用。近年来,大量研究发现,多囊卵巢综合征(PCOS)患者卵泡液内MT水平较低,并且认为MT水平不足可能参与PCOS的发病过程,但两者间的关系及具体作用机制尚未阐明。本文旨在对MT和PCOS的关系展开论述,分析MT在PCOS发病机制中的作用。     

The effect of age and pre-light melatonin concentration on the melatonin sensitivity to dim light.

The hormone melatonin is secreted at night from the pineal gland, with light being a potent inhibitor of its secretion. Age related decreases in plasma melatonin concentrations have indicated that this may be related to pineal calcification with aging. Recently, it was shown that the melatonin sensitivity to light may be a biological marker of bipolar disorder. However, on average, patients were older than the control group in most studies, and it is not known if age has an effect on the melatonin suppression by light. To test this hypothesis, the present study investigated the effect of age on the melatonin sensitivity to dim light (200 lux). Participants were grouped into three age groups. On the testing night, they were placed in a dark room from 21.00 h to 02.30 h. Light exposure was for an hour from midnight to 01.00 h. Blood samples were collected at regular intervals for measurement of plasma melatonin. No significant differences were found in the percentage suppression of melatonin within the age groups defined in the present study (P > 0.5). No correlation was also found between age and percentage suppression of melatonin (r2 = 0.007; P > 0.1). Our results suggest that the melatonin suppression by light (200 lux) is not affected by age.     

Synthesis of RNA in the pineal gland during N-acetyltransferase induction

The biosynthesis of RNA in the cultured rat pineal was monitored during the (l)-isoproterenol-induced increase in N-acetyltransferase activity. Treatment with the β-agonist (l)-isoproterenol elevated pineal N-acetyltransferase activity 30-fold within 6 hr but had no effect on the incorporation of [³H]uridine into total nuclear, total cytoplasmic or total poly(A) containing RNA. Examination of the [³H]uridine-labeled total cytoplasmic RNA and poly(A)-rich messenger RNA by means of agarose gel electrophoresis revealed no significant changes in the synthesis of these RNA species by (l)-isoproterenol treatment of the cultured pineal gland. The lag in the appearance of newly synthesized RNA from the nucleus into the cytosol of the pineal closely corresponds to the lag in the appearance of new N-acetyltransferase activity. These results suggest that, although (l)-isoproterenol may cause a dramatic induction of N-acetyltransferase enzyme activity in the cultured pineal gland, there is no significant alteration in the RNA biosynthesis of the pineal gland to meet the demands of enzyme induction. The induction of N-acetyltransferase activity by (l)-isoproterenol is inhibited by actinomycin D. However, sensitivity to the antibiotic is lost 90–180 min after the initiation of induction by (l)-isoproterenol but 90 min before the accumulation of appreciable enzyme activity.     

松果腺褪黑素对大鼠腹腔巨噬细胞化学发光和脾、下丘脑PGE_2含量的影响

采用松果腺切除术、酵母多糖调理的鲁米诺依赖的化学发光法及前列腺素E_2(PGE_2)放射免疫测定方法观察了松果腺和褪黑索(MT)对大鼠腹腔巨噬细胞化学发光及脾、下丘脑PGE_2含量的影响。结果表明:松果腺切除后大鼠腹腔巨噬细胞化学发光值降低,脾及下丘脑PGE_2含量升高,10～1000 μg·kg~(-1)MT分别恢复之。其中以10μg·kg~(-1)MT作用最强;10μg·kg~(-1)MT还抑制正常大鼠脾及下丘脑PGE_2含量。上述作用可能是松果腺MT对炎症免疫调节作用的部分机制。     

Effect of psychotropic drugs on the contents of melatonin, serotonin and N-acetylserotonin in rat pineal gland

In the dark phase, the effects of the psychotropic drugs on the contents of melatonin, serotonin (5-HT) and N-acetylserotonin (NAS) in rat pineal gland were examined. The pineal gland was removed at a certain period of time after subcutaneous injection of the drugs. 5-HT, NAS and melatonin contents in the pineal gland were determined by high performance liquid chromatography with fluorometric detection. A dose-dependent decrease was observed for melatonin content in the administration of diazepam (DZP), hydroxyzine (HYZ), chlorpromazine (CPZ) or haloperidol (HPD). When imipramine (IPM) or amitriptyline (APL) was given to rats, pineal 5-HT content was significantly decreased. On the other hand, the administration of IPM or APL caused increases in pineal NAS and melatonin. Furthermore, the administration of phenytoin (PYT) revealed no changes in the content of pineal indoleamines. These results suggest that the psychotropic drugs widely used in clinical applications could cause significant changes in pineal indoleamine content.     

Chronic diazepam administration differentially affects melatonin synthesis in rat pineal and Harderian glands

RATIONALE: Pineal and Harderian gland melatonin production as well as plasma melatonin levels were investigated in male Wistar rats (12 weeks old) after administration of diazepam, a benzodiazepine widely used as anxiolytic. OBJECTIVE: The present study investigates the effects of a chronic administration of diazepam on pineal and Harderian gland melatonin contents. METHODS: Diazepam was administered subcutaneously, for 21 days, at a dosage of 3 mg/kg body weight per day, 1 h before the onset of darkness. RESULTS: Diazepam clearly affected pineal melatonin biosynthesis and plasma melatonin levels. Diazepam reduced the pineal melatonin content (by a factor of 2) and the activity of N-acetyltransferase (NAT) (by a factor of 3.5), as well as plasma melatonin levels (by a factor of 1.5), but had no effects on pineal hydroxyindole-O-methyltransferase activity. By contrast to the pineal gland, diazepam failed to affect the Harderian gland melatonin content. CONCLUSIONS: Our results suggest that the inhibition of melatonin production induced by diazepam in vivo may be due to a direct action of this benzodiazepine on the pineal gland, through its action on NAT, the key enzyme of melatonin synthesis, and that the control of melatonin production in the Harderian glands may be different from that observed in the pineal gland.