磁场对丘脑下部一氧化氮含量的影响及与丘脑下部神经内分泌核团的关系

应用硝酸还原酶反应—分光光度法测定和NADPH-d组织化学技术,对磁场处理后丘脑下部一氧化氮量的变化及其可能的原因进行了研究,发现磁场可促使丘脑下部一氧化氮量(OD值)显著升高,并具有显著滞后效应。NADPH-d阳性神经细胞及NADPH-d和血管加压素(AVP)双染阳性神经细胞集中分布在丘脑下部室旁核、室周核和视上核,但不存在 于视交叉上核,提示室旁核、室周核和视上核一氧化氮能神经细胞是丘脑下部的一氧化氮的主要来源。磁场处理后大鼠丘脑下部一氧化氮含量(OD值)较正常对照组显著升高应归因于这些神经细胞受磁场作用表达增强。一氧化氮和血管加压素的共存可能对磁场调节内分泌具有一定意义。     

不同月龄长爪沙鼠视上核加压素分泌的实验

血管加压素(arginine vasopressin,AVP)是下丘脑视上核和室旁核神经元分泌的九肽激素。关于长爪沙鼠不同月龄加压素的分泌状况少见报道。作者采用光镜和电镜、免疫细胞化学和图像分析技术,对不同月龄长爪沙鼠视上核(SON)加压素能神经元加压素的分泌进行了比较研究。结果表明：在H．E染色切片中,各组均可见视上核团呈三角形。免疫细胞化学标记的各组长爪沙鼠中均可见AVP阳性细胞。图像分析数据经统计学处理表明：成龄长爪沙鼠血管加压素的分泌能力较强,幼龄及老龄组分泌能力减弱。     

精氨加压素片段(4-8)对鼠脑PKC和PKA活性的影响

精氨加压素的 C端片段 ,AVP( 4 - 8) ,具有增强记忆的功能 ,它在大鼠脑内引发一系列的生理生化反应 .PKC经常是 G蛋白偶联受体信号传导途径中的介导激酶 ,在 AVP( 4 - 8)信号转导支路中亦不例外 .放射性配基结合实验表明 ,在海马及皮层突触膜上存在 AVP( 4 - 8)的特异性结合位点 .AVP( 4 - 8)可以刺激大鼠脑内 PKC酶活的升高 ,并可以被 AVP( 4 - 8)的受体拮抗剂 ZDC( C) PR阻断 .在同样条件下 ,AVP( 4 - 8)对 PKA酶活无显著性影响 .     

水通道蛋白AQP2翻译后修饰及表达调控

AQP2(aquaporin-2)是一种水通道蛋白,表达于集合管的主细胞,其活性主要受抗利尿激素(arginin vasopressin,AVP)调控。AVP调节的AQP2数量和细胞内定位在维持机体水代谢平衡和尿液浓缩中发挥着决定性的作用。AQP2受多种修饰,如磷酸化、泛素化、糖基化等。本文根据最新的文献报道,着重介绍了AQP2翻译后修饰及调控机制。     

从分子水平探索旋转恒定磁场对机体作用之机理

用RCMF旋磁治疗装置研究磁场对信息物质的影响,放射免疫测定发现磁场促使血浆内啡肽显著升高;荧光分光光度法和ELISA法测定发现磁场可以显著抑制5-HT及顺铂等中枢性致呕药物引起的呕吐反应,并同步伴有脑组织、小肠组织5-HT水平的可逆性下降.磁场处理对小鼠5-HT水平的影响表现出明显的窗口效应和滞后效应,磁场对药物致呕的抑制效应与其对5-HT的下调水平有平行相关关系.提示磁场对体内5-HT水平的降低,可能是其抑制细胞毒性化疗药物致呕的内在基础.应用硝酸还原酶反应-分光光度法和NADPH-d组织化学技术,发现磁场可促使丘脑下部一氧化氮(NO)含量显著升高,并具有显著滞后效应. NADPH-d阳性神经细胞及NADPH-d和血管加压素(AVP)双染阳性神经细胞集中分布在丘脑下部室旁核、室周核和视上核,但不存在于视交叉上核,提示室旁核、室周核和视上核一氧化氮肽能神经细胞是丘脑下部的一氧化氮的主要来源.磁场处理后大鼠丘脑下部一氧化氮含量较正常对照组显著升高应归因于这些神经细胞受磁场作用表达增强.一氧化氮和血管加压素的共存可能对磁场调节内分泌具有一定意义.发现磁场可促使肾上腺一氧化氮量显著升高,并维持一定时间,神经肽Y免疫细胞化学染色强度增强,进而对其相关机制和意义进行了讨论.     

加压素和催产素在中枢神经系统中的作用

加压素(AVP)和催产素(OT)是密切相关的2种肽,它们的基因均位于人类第20条染色体上。来自于神经垂体分泌的AVP和OT直接释放到循环系统,调节靶细胞的活动:来自于中枢轴突末梢释放AVP和OT遍布整个中枢神经系统,作为神经递质或调制调节神经细胞的活动,在特定脑区与记忆及精神上的疾病有关。研究AVP和OT在中枢神经系统中的作用,不仅有助于揭示精神分裂症、抑郁、酗酒、老年性痴呆、帕金森氏病等的致病机理,而且对揭示人类社会婚配制度的神经生物学机制提供参考资料。     

非鸣禽丘脑听区和内分泌下丘脑区神经通路的免疫组织化学研究

应用神经示踪物BDA(biotinylated dextran amine)和免疫组织化学方法对环鸽(streptopelia risoria)丘脑听区和下丘脑内分泌脑区间的神经通路进行了研究。结果发现,丘脑卵形核壳 (Ov shell)及周围区域存在丰富脑啡肽免疫反应神经元。丘脑卵形核尾侧(Ovp)有传出纤维直接投射至Ov壳和下丘脑腹内侧核(VMN)。卵形核壳周围和下丘脑内分泌脑区间的传出神经通路显示了丰富的脑啡肽阳性免疫反应细胞和终末标记,在下丘脑腹内侧核中亦存在大量脑腓肽终末标记。结果提示Ov周围的部分脑啡肽神经元发出的传出纤维可能参与了鸽丘脑听区向内分泌下丘脑区投射的神经通路。     

青春期社会奖赏行为性别差异的催产素和多巴胺调控机制

社交互动的奖励特性对于社会行为的表达和适应性社会关系的发展至关重要。当个体受到应激时会导致奖赏系统异常而缺乏社会交往,出现情绪障碍并具有性二态。青春期发育中社会奖赏行为存在显著的性别差异,男性对社会奖赏敏感性大于女性;相反,女性对社会惩罚的敏感性高于男性。在青春期发育过程中,催产素/加压素(OT/AVP)、多巴胺(DA)系统在奖赏环路的性别差异及OT/AVP受体基因表达的多态性,是奖赏行为及情绪障碍性二态的原因,揭示OT-社会奖赏-情绪障碍性二态三者交互作用的神经机制,对开展精神疾病治疗有重要指导意义。     

催产素和加压素与应激的关系

催产素和加压素是由下丘脑视上核和室旁核大细胞性神经内分泌细胞合成和分泌的一种神经垂体激素。各种应刺激都可以引起催产素和加压素神经元的活动。目前应激后引起的这类神经活动的变化与人类的某结疾病的病理生理相关联正在引起人们的关注。西文总结了近几年在这方面的研究进展。主要内容包括：（1）催产素和加压素神经元在应激中的反应;（2）在大细胞性催产素和加压素神经元的应激反应相关联的神经传递物质;（3）与应激相关联的精神疾病的关系。     

哺乳动物交感神经系统内发现类加压素多肽

最近,英国的Hanley等发现,在哺乳动物交感神经系统中,广泛分布着一种有加压素(VP)生物活性和免疫反应性的类加压素多肽(VLP),它存在于神经节的去甲肾上腺素(NE)神经元中,也存在于这些神经纤维支配的组织中。应用精氨酸加压素(AVP)的高特异抗血清测出,腹腔神经节中VLP含量只有颈上神经节的1/4,提示VLP在交感链内的水平可能同VIP一样,也有头端高于尾端的差异。在垂体不能分泌AVP的Brattleboro大鼠的颈上神经节也发现VP样免疫反应性,说明这种VP不是垂体分泌的VP。     

模拟高原低氧对不同性别新生大鼠下丘脑 CRF和AVP水平的影响

目的:探讨高原低氧对雌雄新生大鼠下丘脑-腺垂体-肾上腺皮质轴中枢部位肽能神经元发育的影响.方法:在低压氧舱中模拟高海拔低氧,用放免法测定精氨酸加压素(AVP)和下丘脑促肾上腺皮质激素释放激素(CRF)含量.结果:无论是在2 300 m对照海拔,还是在5 000 m模拟海拔,雌雄生后大鼠具相同的发育模式.低氧下发育至21 d时,CRF水平显著低于对照;相反,21 d及28 d时,低氧组AVP水平高于对照.结论:下丘脑CRF和AVP神经元间不同的发育模式可能与它们的功能及发育阶段特性相异有关.     

新生大鼠下丘脑CRF和AVP神经元对急性低氧的应答

目的:观察肾上腺摘除新生大鼠下丘脑促肾上腺皮质激素释放激素(CRF)和精氨酸加压素(AVP)神经元对急性低氧的应答.方法:在低压氧舱中模拟高海拔低氧,用放免法测定AVP和CRP含量.结果:新生大鼠暴露于急性低氧环境下(模拟5 000 m和7 000 m海拔高度,24 h),其下丘脑CRP在3 d和7 d龄大鼠中无明显变化,但14d、21 d和28 d时低于对照;下丘脑AVP在3 d大鼠中亦无变化,但14 d时低于对照,7 d、21 d及28 d时高于对照.两者对低氧的应答模式随日龄而变化.摘除肾上腺后,14 d、21 d及28 d大鼠下丘脑CRF和AVP含量均显著低于同龄完整大鼠,此时暴露于急性低氧环境下,CRF和AVP无进一步的变化.结论:摘除肾上腺抑制下丘脑CRF和AVP的发育,影响它们对低氧应激的正常应答.     

The effects of ghrelin/GHSs on AVP mRNA expression and release in cultured hypothalamic cells in rats

Ghrelin, the endogenous ligand for growth hormone secretagogues (GHSs) receptor (GHS-R), increases adrenocorticotropin (ACTH) and cortisol (corticosterone) as well as GH secretion in humans and animals. However, the site of GHSs action to induce ACTH secretion is not fully understood. To clarify the mechanisms of the action of ghrelin/GHSs on ACTH secretion, we analyzed the effects of KP-102 and ghrelin on the mRNA expression and release of corticotropin releasing factor (CRF) and arginine vasopressin (AVP), ACTH secretagogues, in monolayer-cultured hypothalamic cells of rats. Incubation of cells with KP-102 for 4 h and 8 h and with ghrelin for 4 h significantly increased AVP mRNA expression and release without changing CRF mRNA expression. CRF levels in culture media were undetectable. Suppression of GHS-R expression by siRNA blocked ghrelin- and KP-102-induced AVP mRNA expression and release. NPY significantly increased AVP mRNA expression and release. Furthermore, treatment of cells with anti-NPY IgG blocked KP-102-induced AVP mRNA expression and release. We previously reported that KP-102 significantly increases NPY mRNA expression in cultured hypothalamic cells. Taken together, these results suggest that ACTH secretion by ghrelin/GHSs is induced mainly through hypothalamic AVP, and that NPY mediates the action of ghrelin/GHSs.     

蛙皮素对大鼠IFN性发热反应及脑内AVP含量的影响

目的:研究蛙皮素(BN)能否拮抗大鼠干扰素(IFN)性发热反应及其可能机制的探讨.方法:建立大鼠IFN-α性发热模型,观察侧脑室注射BN对大鼠IFN-α性发热反应及下丘脑、脑腹中隔区(VSA)精氨酸加压素(AVP)含量的影响.结果:①侧脑室注射IFN-α(每只2、5、8×104U)引起剂量依赖性体温升高,同时测得VSA中AVP含量明显增加(P<0.05),下丘脑AVP含量无明显变化(P>0.05).②侧脑室注射BN(每只0.1、0.5 μg),引起剂量依赖性体温降低(P<0.01),同时测得VSA中AVP含量增加( P<0.05),下丘脑AVP含量无明显变化(P>0.05).③侧脑室注射IFN-α(每只5×104U)30 min后,侧脑室注射BN(每只0.5 μg),BN能逆转大鼠发热反应(P<0.05),并于150 min时,大鼠体温恢复到对照组水平,同时测得VSA中AVP含量与对照组无显著性差异(P>0.05).结论:内生性AVP可能参与了IFN-α性发热反应的调节;BN降正常体温及解热作用可能通过AVP介导完成的.     

Thirst impairment elicited by intraventricular administration of vasopressin antagonists

To determine whether centrally released vasopressin influences thirst, observations of osmotic thirst threshold, osmotic load excretion and postloading restitution of plasma osmolality were made in dogs in control experiments and during infusion of AVP antagonists into the third ventricle. Significant elevation of osmotic thirst threshold was elicited by infusion of d(CH₂)₅AVP at a rate of 0.2–2.0 μg·min⁻¹ and of d(Et₂)AVP at a rate of 0.3 μg·min⁻¹ (V₁ antagonists, weak V₂ agonists) as well as by administration of d(CH₂)₅[D-Ile²,Abu⁴]AVP at a rate of 0.4 μg·min⁻¹ (potent V₂ antagonist, weak V₁ antagonist). Administration of d(CH₂)₅AVP at a rate of 2.0 μg·min⁻¹ was associated with a significant suppression of the postloading water intake and osmotic load excretion and with a delay in restitution of plasma osmolality. These findings indicate that centrally released vasopressin may participate in the control of thirst.     

头端延髓腹外侧区血管加压素在刺激中脑dPAG区诱发防御性升压反应中的作用

雄性Sprague－Dawey大鼠,用乌拉坦（70mg/kg）和氯醛糖（30mg／kg）腹腔麻醉。在双侧头端延髓腹外侧区（rVLM区）每侧微量注射血管加压素（AVP）（10pmol／o.1μl）可引起平均动脉压（MBP）升高,心率（HR）变化不明显,每侧微量注射AVP的V1受体拮抗利d（CH2）5[Tyr(Me)2]AVP（0.1nmol／0.1μl）后MBP和HR无明显变化。若预先在rVLM区每侧微量注射AVP的V1受体拮抗剂（0.1nmol/0.1μl）后,再在rVLM区同一部位每侧注入AVP（10pmol／0.1μl）,MBP升高作用消失。电刺激中脑（dPAG区）可诱发防御性升压反应。若在双侧rYLM区每侧微量注射AVP的V1受体拮抗剂（0.1nmol／0.1μl）可对防御性升压反应起部分抑制作用。结果表明,rVLM区内微量注射AVP可引起MBP升高,刺激中脑dPAG区诱发的升压反应均与rVLM区AVP的V1受体的激活有关。     

延髓头端腹外侧区血管升压素能机制在应激性高血粘度中的作用

观察延髓头端腹外侧区（ｒＶＬＭ）微量注射血管升压素（ＡＶＰ）能否影响正常大鼠的血压和血粘度,并分析ｒＶＬＭ内ＡＶＰ能机制在清醒大鼠经悬吊加束缚引起应激性升压反应和高血粘度中的影响。结果如下：⑴正常大鼠双侧ｒＶＬＭ微量注射ＡＶＰ（每侧０．５μｇ／０．５μｌ）,可引起血压和血粘度升高;此作用可被事先在同一位置微量注射ＡＶＰ－Ｖ１受体拮抗剂ｄ（ＣＨ２）５「Ｔｙｒ（Ｍｅ）＾２」ＡＶＰ（每侧０．１μｇ／０．     

Influences of isotonic, hypertonic and hypovolemic treatments on vasopressin response and fluid-electrolyte balance in l-thyroxine-induced hyperthyroid rat

The present study was performed to determine how l-thyroxine-induced hyperthyroidism affects the vasopressin response to different stimulations (isotonic, hypertonic and hypovolemic) in rats. Spraque-Dawley rats were initially separated into 3 groups; control (n=24), sham hyperthyroidism (n=24, hyperthyroidism (n=24). At the end of the experiment additional sub-groups were formed before decapitation. These sub-groups were formed as; without stimulation (n=6), isotonic stimulation (n=6), hypertonic stimulation (n=6) and hypovolemic stimulation (n=6). Total T3, total T4 and AVP levels were evaluated in the plasma. Haematocrit and osmolality levels were also determined. When the parameters related to thyroid hormones were evaluated, it was determined that total T3 and T4 levels were higher in hyperthyroid group than the other groups. Plasma AVP levels showed more increase in hyperthyroid group both in basal grade and against to hypertonic and hypovolemic stimulations than the other groups (P<0.001). The results of the present study indicate that l-thyroxine-induced experimental hyperthyroidism increased basal and stimulated AVP release in rats.     

Low power microwave interaction with phospholipase C and D signal transduction pathways in myogenic cells

Ionic channel proteins are possible sites of microwave interaction at the cell membrane level. Patch-clamp data, using single channel and total current recording, indicated that low level microwave fields may modify some functional parameters of the nicotinic acetylcholine receptor in primary chick myotubes, suggesting a possible effect of microwaves on myogenic cells. Here, we investigated the biological relevance of such results, in relation to the possible involvement of intracellular signaling processes. We exposed L6-C5 myogenic cells to low power electromagnetic fields and observed the consequences on hormonal activation of phospholipases C and D. We found that increased inositol phospholipid turnover, induced by acetylcholine and arginine vasopressin activation of phospholipase C, was not modified in microwave irradiated myoblasts or myotubes. Moreover, vasopressin-dependent phospholipase D activation, assessed by measuring the [3H]-free choline release, was not modified by microwave irradiation. Our conclusions suggest that low level microwave fields do not modify signal transduction pathways activated by acetylcholine and vasopressin in L6-C5 myogenic cells.     

3H]desGly-NH2(9)-d(CH2)5[D-Ileu2,Ileu4]AVP: an AVP V2 receptor antagonist radioligand

Binding characteristics of the selective V₂ antagonist radioligand [³H]desGly-NH₂⁹-d(CH₂)₅[D-Ileu²,Ileu⁴]AVP to rat kidney were determined. Binding was specific, saturable and reversible. The peptide bound to a single class of high-affinity binding sites with B_max 69.4±6.8 fmol/mg protein and K_D 2.8±0.3 nM. AVP and other related peptides displaced [³H]desGly-NH₂⁹-d(CH₂)₅[D-Ileu²,Ileu⁴]AVP binding. The order of potency of inhibition was desamino-D-AVP > AVP > d(CH₂)₅[D-Ileu²,Ileu⁴]AVP > oxytocin > d(CH₂)₃[Tyr(Me)²]AVP > d(CH₂)₅[sarcosine⁷]AVP, which is typical of a selective V₂ radioligand. Autoradiographic localization of [³H]desGly-NH₂⁹-d(CH₂)₅[D-Ileu²,Ileu⁴]AVP binding sites in kidney showed dense binding in the inner and outer medulla with less binding in the cortex, which is consistent with known renal V₂ receptor distribution.