蓝莓对免疫性肝纤维化大鼠细胞色素P4502E1表达的影响

目的 观察蓝莓对大鼠免疫性肝纤维化的预防作用及其对细胞色素P4502E1 (CYP2E1)表达的影响.方法 将50只健康清洁级Wistar大鼠随机分为正常对照组(A组)、肝纤维化模型组(B组)、蓝莓原浆预防组(C组)、复方鳖甲软肝片预防组(D组)、蓝莓原浆加复方鳖甲软肝片预防组(E组)共5组,每组10只.除正常对照组外,其余各组均腹腔注射猪血清制备大鼠肝纤维化模型,各预防组在造模同时分别给予蓝莓原浆或(和)复方鳖甲软肝片灌胃,1次/d,共12周.12周末处死大鼠,行肝脏病理组织学检查,测定各组大鼠血清ALT水平、肝组织匀浆超氧化物歧化酶(SOD)活性、丙二醛(MDA)及羟脯氨酸(Hyp)含量,采用实时荧光定量聚合酶联反应、Western blot和免疫组织化学法检测大鼠肝组织CYP2E1的mRNA及蛋白质表达. 结果 12周末处死大鼠,A、B、C、D、E各组大鼠血清ALT水平分别为(37.9±4.5) U/L、(49.2±9.8) U/L、(39.9±6.3) U/L、(40.5±5.7) U/L及(38.2±8.4)U/L,各组间差异无统计学意义;各预防组大鼠肝纤维化程度较B组明显减轻(F=95.097,P＜0.05); C、D、E各组大鼠肝组织匀浆Hyp分别为(472.7±44.1)μg/g、(416.1±39.4)μg/g和(429.5±55.1)μg/g,低于B组的(603.2±68.9) μg/g,F=39.315,P＜0.05,差异有统计学意义; SOD水平分别为(2.5±0.4) U/mg、(2.0±0.5)U/mg、(2.2±0.2) U/mg,高于B组的(1.6±0.4) U/mg,F=25.557,P＜0.05,差异有统计学意义;MDA分别为(0.83±0.06) mol/mg、(0.96±0.08) nmol/mg、(0.85±0.06)nmol/mg,低于B组的(1.24±0.15)nmol/mg,F=46.376,P＜0.05,差异有统计学意义;B、C、D、E组大鼠肝组织CYP2E1的mRNA及蛋白质表达高于A组,C、D、E组大鼠肝组织CYP2E1的mRNA及蛋白质表达低于B组,但差异均无统计学意义.结论 蓝莓对猪血清所致大鼠肝纤维化有一定的预防作用;免疫性肝纤维化时,大鼠肝组织CYP2E1的表达无明显改变;蓝莓对CYP2E1的表达无明显影响.     

蓝莓对肝纤维化大鼠血红素加氧酶-1表达的影响

目的 观察蓝莓对大鼠肝纤维化的预防作用及对血红素加氧酶-1(HO-1)表达的影响.方法 45只SD大鼠随机分为生理盐水对照组(A组)、模型组(B组)、蓝莓汁预防组(C组)、丹芍化纤胶囊预防组(D组)及蓝莓汁加丹芍化纤胶囊预防组(E组),每组9只.CCl4复合因素制备大鼠肝纤维化模型,各预防组给予蓝莓汁或(和)丹芍化纤胶囊灌胃,共饲养8周.测定各组大鼠血清ALT水平及肝组织匀浆中超氧化物歧化酶(SOD)和丙二醛(MDA)的表达,并进行肝组织病理学检查.采用实时荧光定量聚合酶链反应、免疫组织化学法和Western blot分析大鼠肝组织HO 1的mRNA及蛋白质表达.多组间数据比较用单因素方差分析,等级资料用秩和检验.结果 B组大鼠血清ALT水平高于A组[(203.25±31.62)U/L比(57.25±6.88)U/L,F=92.498,P＜0.05)],各预防组较B组明显减少[C、D和E组分别为(149.44±16.51)U/L、(136.88±10.07)U/L和(127.38±11.03)U/L,F=92.498,P＜0.05)].C、D、E组大鼠肝组织匀浆SOD水平分别为(1.36±0.09)U/mg、(1.42±0.13)U/mg、(1.50±0.15)U/mg,高于B组的(1.08±0.19)U/mg(F=13.671,P＜0.05);MDA水平分别为(0.294±0.026)nmol/mg、(0.285±0.025)nmol/mg、(0.284±0.028)nmol/mg,低于B组的(0.335±0.056)nmol/mg(F=20.809,P＜0.05).各预防组肝纤维化程度较B组也有所减轻(x2-24.956,P＜0.05).B组大鼠肝组织HO-1的mRNA和蛋白质表达高于A组(F值分别为4.549和22.926,P值均＜0.05),各预防组大鼠肝组织HO-1的mRNA和蛋白质表达均高于B组,但差异无统计学意义(P＞0.05).结论 蓝莓对CCl4所致大鼠肝纤维化有一定的预防作用;在慢性肝损伤时,蓝莓对HO-1的表达无明显影响.     

小茴香精油对肝纤维化大鼠抗氧化应激损伤作用的研究

目的 评价小茴香精油在肝纤维化大鼠模型中抗氧化应激损伤及抗肝纤维化的作用.方法 肝纤维化模型的构建.SD大鼠皮下注射4ml/kg四氯化碳橄榄油溶液,同时给予高脂低蛋白饲料共5周.设空白对照组(A组)8只,正常饲养;预防阶段模型对照组(B组)10只,造模同时给予等渗盐水灌胃;小茴香预防组(C组)10只,造模同时给予小茴香精油灌胃,剂量为3 ml/kg ;治疗阶段模型对照组(D组)22只,造模后给予等渗盐水灌胃;小茴香治疗组(E组)22只,造模后给予小茴香精油灌胃,剂量为3 ml/kg;扶正化瘀对照组(F组)22只,造模后给予扶正化瘀胶囊与等渗盐水悬混液灌胃,剂量为0.4 g/kg.分别于第5周末处死A、B、C组大鼠,第6、7、8、9周末处死D、E、F组各4～6只大鼠.检测血清ALT、AST、透明质酸、层黏蛋白、8-羟基-2-脱氧鸟嘌呤含量,肝组织匀浆超氧化物歧化酶、谷胱甘肽过氧化物酶、丙二醛.肝组织行HE染色、马松染色和α平滑肌肌动蛋白免疫组织化学染色.计量资料先进行正态性检验和方差齐性检验,满足方差分析条件时采用两因素析因设计的方差分析,差异有统计学意义后两两比较采用LDL检验.不满足方差分析条件和等级资料采用秩和检验.结果A、B、C3组超氧化物歧化酶活力差异有统计学意义(286.33±37.90) U/mg、(242.22±33.21) U/mg、(323.78±53.16) U/mg, F=8.649,P=0.002);谷胱甘肽过氧化物酶分别为(297.25±54.29) U/mg、(148.62±15.57) U/mg、(221.65±53.39)U/mg(F=26.468,P=0.000);丙二醛分别为(1.01±0.37) nmol/mg、(4.29±1.85) nmol/mg、(2.00±0.42) nmol/mg (F=18.13,P=0.000);8-羟基-2-脱氧鸟嘌呤含量含量为(35.44±2.19) ng/L、(50.25±8.29) ng/L、(39.20±4.00) ng/L(F=16.332,P=0.000).炎症活动度在C组明显低于B组(Z=-2.29,P=0.022);E组轻于D组(Z=-2.51P=0.012),F组轻于D组(Z=-2.30,P=0.021);纤维化分期E组与D组差异有统计学意义(Z=-2.81,P=0.005),F组与D组比较差异有统计学意义(Z=-2.59P=0.015).结论 小茴香精油具有减轻肝脏炎症反应、防治肝纤维化进展的作用,其机制可能与抗氧化应激损伤有关.     

α-2a干扰素对大鼠肝组织bcl-2基因表达的影响及意义

目的:探讨α-2a干扰素(IFNα-2a)对大鼠肝组织bcl-2基因表达的影响和对肝纤维化的作用及其机制.方法:将SD大鼠随机分成纤维化模型组(A组,CCl4诱导形成大鼠肝纤维化模型),对照组(B组)及IFNα-2a干预组(C组).用RT-PCR法检测各组大鼠肝脏bcl-2的表达,常规HE和网状纤维染色检测肝组织标本.结果:C组纤维化程度及肝细胞脂肪变性较A组显著减轻,但肝组织炎症改变无显著差异性.C组bcl-2基因蛋白表达显著低于A组(P<0.01),但显著高于B组bcl-2基因蛋白表达的量(P<0.01).结论:IFNα-2a能够阻断CCl4诱导的肝纤维化和减少肝脂肪变性.其机制与bcl-2基因表达有关,可能通过调节bcl-2基因表达与HSC凋亡,从而阻断肝纤维化和减少肝脂肪变性.     

黏附分子在沙利度胺所致大鼠肝纤维化中的作用机制

目的:观察沙利度胺对大鼠实验性肝纤维化的治疗效果并探讨其作用机制.方法:四氯化碳腹腔注射制备大鼠肝纤维化模型后,应用沙利度胺(100 mg/kg)ig分别治疗2、4、6 wk作为动态观察时相点.HE染色观察肝组织病理变化,放射免疫法检测血清透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PC Ⅲ)和Ⅳ型胶原(CⅣ)的表达,免疫组织化学法检测细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1(VCAM-1)和E-选择素(E-selectin)蛋白质的表达,逆转录聚合酶链反应法检测ICAM-1、VCAM-1和E-selectin mRNA的表达.结果:与肝纤维化组相比,沙利度胺治疗4wk、6 wk能显著降低大鼠肝组织纤维化积分,显著降低血清HA(176.6±7.5 μg/L,173.8±6.7 μg/L vs 486.9±12.4 μg/L)、LN(38.4±5.8 μg/L,34.7±7.3 μg/L vs 84.5±5.2 μg/L)、PC Ⅲ(44.3±5.5 μg/L,40.2±6.1 μg/L vs 65.0±5.6μg/L)、CⅣ(31.8±6.7 μg/L,30.4±5.7 μg/L vs 55.6±6.5 μg/L)的含量(P＜0.05),沙利度胺治疗2 wk 4 wk,6 wk组均可显著降低ICAM-1、VCAM-1和E-selectin蛋白和mRNA的表达(P＜0.05).结论:沙利度胺可通过下调ICAM-1、VCAM-1和E-selectin表达水平而发挥抗肝纤维化作用.     

IFNα-2a对CCl4诱导肝纤维化的作用及影响因素

目的:观察干扰素α-2a(interferon alfa-2a,IFNα-2a)对CCl4诱导肝纤维化的作用及影响因素.方法:建立CCl4诱导大鼠肝纤维化模型,SD雌性大鼠50只,分成5组,每组10只,即生理盐水对照组(A组)、纤维化模型组(B组)、6×104 U/kg IFNα-2a干预组(C组)、12×104 U/...     

MEGX试验对肝脏储备功能评估价值

目的:探讨单乙基甘胺酰二甲苯胺(MEGX)试验对肝脏储备功能评估的价值.方法:采用改良复合因素(CCl4、胆固醇、乙醇)制备大鼠肝硬化模型,将40只雄性肝硬化大鼠完全随机分成A、B、C、D组4组,每组10只,分别行不同肝切量的肝切除(0%、15%、30%、45%).术前、术后行MEGX试验、吲哚氰绿排泄(ICGR15)试验、常规肝功能检测,并对切除的肝组织进行常规病理检查.结果:实验组(B、C、D组)肝切后大鼠血清MEGX的量较肝切前均有不同程度的下降(30.22±10.6 μg/L vs 37.52±14.01 μg/L,22.68±6.19 μg/L vs 38.47±15.24 μg/L,12.60±5.88μg/L vs 37.26±13.87 μg/L,均P<0.05).且随着肝切量的增加,MEGX的量明显减少,术后各组间比较均有显著性差异(P<0.05).结论:MEGX试验能较灵敏反映肝储备功能受损的程度,优于常规肝功能检测及ICGR15试验.     

丹芍化纤胶囊对肝纤维化大鼠PDGFR-β和p-ERK1/2的影响

目的通过观察丹芍化纤胶囊对肝纤维化大鼠PDGFR-β和p-ERK1/2的影响,探索其抗肝纤维化的可能机制.方法♂SD大鼠55只,体质量180-220 g,随机分为正常组、模型组、预防组.除正常组外,其余均采用四氯化碳、高脂饮食及乙醇复合因素复制肝纤维化模型,造模同时预防组每日一次予以0.8 g/kg丹芍化纤自来水悬液灌胃,模型组、正常组予以等体积自来水灌胃,持续8 wk.造模结束后肝组织HE染色病理检查,免疫组化检测肝组织PDGFR-β、蛋白印迹检测肝组织p-ERK1/2在各组表达,生化法检测各组血清透明质酸(HA)、层黏蛋白(LN)、Ⅲ型前胶原(PⅢP)、白蛋白(ALB)、总蛋白(TP),计算白球比(A/G).结果造模8 wk后经病理学证实模型大鼠形成典型的肝纤维化,模型成功.与正常组相比,模型组肝组织PDGFR-β、p-ERK1/2及血清HA、LN、PⅢP均有显著升高,ALB、A/G显著降低(PDGFR-β1 84.6±8.5 vs 89.6±5.8,P＜0.05;p-ERK1/2360.0±14.5 vs 15.4±2.1,P＜0.05;HA517.5±91.5 μg/L vs 254.4±33.1 μg/L,P＜0.05;LN58.4±11.3 μg/L vs 37.3±9.8 μg/L,P＜0.05;PⅢP36.9±5.6 μg/L vs 4.7±1.5 μg/L,P＜0.05;ALB27.4±4.9 g/L vs 42.1±1.6 g/L,P＜0.05;A/G0.89±0.08 vs 1.38±0.09,P＜0.05);与模型组相比,预防组肝组织PDGFR-β、p-ERK1/2及血清HA、LN、PⅢP均有显著降低,ALB、A/G显著升高(PDGFR-β91.1±6.3vs 184.6±8.5,P＜0.05;p-ERK1/2253.8±18.2vs 360.0±14.5,P＜0.05;HA322.9±41.4 μg/Lvs 517.5±91.5 μg/L,P＜0.05;LN46.0±9.4μg/L vs 58.4±11.3 μg/L,P＜0.05;PⅢP14.5±2.4 μg/L vs 36.9±5.6 μg/L,P＜0.05;ALB37.2±2.8 g/L vs 27.4±4.9 g/L,P＜0.05;A/G1.18±0.13 vs 0.89±0.08,P＜0.05).结论PDGFR-β及p-ERK1/2在肝纤维化形成中起重要作用,丹芍化纤胶囊具有良好的预防肝纤维化形成的作用,其降低PDGFR-β及p-ERK1/2在肝组织的表达可能是其作用机制之一.     

四甲基吡嗪对肝纤维化大鼠肝组织中肌细胞增强因子2A表达的影响

目的:观察四甲基吡嗪对肝纤维化大鼠肝组织中肌细胞增强因子2A(myocyte enhancer factor2A,MEF2A)表达的影响.方法:以SD大鼠为实验对象,采用60%四氯化碳(CCl4)皮下注射(0.3ml/ 100g体重,每周两次),复制CCl4肝纤维化动物模型.四甲基吡嗪预防组和四甲基吡嗪治疗组分别自造模之日起和造模开始后第31天给予四甲基吡嗪(10mg/ 100g体重,灌胃,1次/d).实验第12周取肝组织,采用实时荧光定量PCR法检测各组动物肝组织中MEF2A mRNA表达水平;用Western blot检测各期动物肝组织中MEF2A与α-平滑肌肌动蛋白(α-smooth muscle action,α-SMA)含量.结果:与正常组大鼠相比,模型组大鼠肝组织中的MEF2A mRNA和蛋白及α-SMA表达增高(P＜0.01),四甲基吡嗪预防组和四甲基吡嗪治疗组大鼠上述指标高于正常组,但均低于模型组(P＜0.01,P＜0.05);大鼠肝组织中MEF2A和α-SMA表达呈正相关.结论:MEF2A表达强弱与肝纤维化程度相关,四甲基吡嗪能有效减轻CCl4诱导的大鼠肝纤维化,有效抑制MEF2A的表达.     

益肝煎剂对实验性肝纤维化大鼠I,Ⅲ型胶原蛋白表达的影响

目的探讨益肝煎剂对实验性肝纤维化大鼠肝脏Ⅰ、Ⅲ型胶原蛋白表达的影响.方法采用400mL@L-1四氯化碳(CCl4)sc制备大鼠实验性肝纤维化模型,将80只(雌雄各半)Wistar大鼠随机分成正常对照组(A组)、模型对照组(B组)、秋水仙碱组(C组)和益肝煎剂组(D组)各20只.后两组于造模的同时开始给药,观察10 wk.采用苦味酸-天狼星红(Picric acid-Sirius red)染色显示Ⅰ,Ⅲ型胶原.偏振光显微镜下区分Ⅰ,Ⅲ型胶原.用半定量评分方法判断细胞变性程度和纤维化程度.结果益肝煎剂组大鼠肝组织的脂肪变性程度较模型组明显减轻,脂肪变性积分分别为2.00±1.36和3.17±0.75(P＜0.01);Ⅰ,Ⅲ型胶原蛋白含量明显少于模型组,纤维化程度积分分别为1.32±0.57和2.33±0.82(P＜0.01).结论益肝煎剂对大鼠实验性肝纤维化的形成有明显抑制作用.     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.