内源性精氨酸加压素在昼光期大鼠紧张性体温调节中的作用

目的: 探讨内源性精氨酸加压素(AVP)在昼光期大鼠紧张性体温调节中的作用及其机制。方法: 使用成年雄性SD大鼠,在22 ℃环境温度下,明暗时间各12 h,同步无线遥测体核温度(Tc)和棕色脂肪(BAT)温度。上午10:00给大鼠腹腔注射AVP(10 μg/kg)或精氨酸加压素V_1a(AVP V_1a)受体阻断剂(30 μg/kg)。用酶联免疫吸附测定法,分别检测昼光期和暗光期大鼠血浆中AVP浓度。给AVP 60 min 后测定血清中甘油三酯、游离脂肪酸和甘油浓度变化。给予AVP后间隔10 min 记录大鼠的理毛活动。结果: (1)在昼光期中AVP V_1a受体阻断剂能够升高Tc和BAT温度。(2)在昼光中Tc和BAT温度处于低温期时,血浆中AVP水平则明显提高。(3)腹腔注射AVP引起Tc快速降低时,伴有BAT温度明显降低和大鼠的理毛行为明显增加。(4)AVP可以降低血清游离脂肪酸与甘油浓度,提高血清甘油三酯的浓度。结论: (1)内源性AVP通过AVP V_1a受体参与昼光期大鼠紧张性体温调节过程,因为在昼光期中不仅血浆AVP浓度明显高于暗光期,而且AVP V_1a受体阻断剂也能明显升高Tc和BAT温度。(2)AVP能降低BAT温度、血中游离脂肪酸和甘油浓度,提高理毛活动,证明AVP引起低温的机制可能与抑制脂肪分解、降低BAT产热和提高散热反应有关。     

精氨酸加压素翻转脂多糖引起大鼠发热及其对痛觉敏感性的影响

目的:研究外周给精氨酸加压素(AVP)对脂多糖(LPS)引起的大鼠发热和痛觉过敏的影响,以及与血清中IL-1β和PGE_2水平变化的关系。方法:实验用成年雄性SD大鼠,在23℃环境温度下,明暗时间各12 h。用无线遥测系统连续测量大鼠体核温度(Tc)、棕色脂肪温度(T_(BAT))和活动。10:00或11:30分别给大鼠腹腔注射LPS(50μg/kg)、AVP(10μg/kg)或V1a受体阻断剂(30μg/kg)。用ELISA法测定血清IL-1β和PGE_2的含量。用足底痛觉测试仪(Hargreaves test)测试大鼠热痛缩爪潜伏期的变化。结果:(1)腹腔注射LPS引起大鼠双相发热过程伴有痛觉过敏现象。(2)AVP能够翻转LPS引起的Tc和T_(BAT)升高反应,降低发热引起的痛觉敏感性。(3)外周给V1a受体阻断剂能提高LPS引起的发热反应,但不影响发热引起的痛觉敏感性变化。(4)AVP能抑制LPS引起的发热大鼠血液中IL-1β和PGE_2水平升高。结论:(1)外周给予AVP可通过抑制棕色脂肪产热以及降低血液中IL-1β和PGE_2的浓度而翻转LPS发热反应并降低发热伴随的痛觉敏感性升高现象。(2)内源性AVP也有限制LPS发热的作用,但可能不影响发热引起的痛觉阈值降低现象。     

内源性精氨酸加压素在索曼引起的大鼠体温降低中的作用

目的:探讨内源性精氨酸加压素是否参与索曼引起的降温过程。方法:用数字体温计测量大鼠的体温,每次间隔60 min,观察了腹腔注射AVP V₁受体阻断剂(30 μg/kg)对皮下注射索曼(60 μg/kg)引起大鼠降温效应的影响,以及给索曼后2 h血浆中AVP含量的变化。结果:给索曼后可引起明显的体温降低,在给药后7 h体温恢复到基线水平。AVP V₁受体阻断剂能明显阻断索曼的降温效应。在给索曼后2 h血浆中AVP浓度明显提高。结论:实验结果证明内源性AVP参与索曼引起的降温过程。     

AVP V1阻断剂对有机磷杀虫剂毒死蜱降温效应的阻断作用

目的给动物口饲有机磷农药杀虫剂毒死蜱(CHP)先出现快速的降温相,然后出现发热相.众所周知精氨酸加压素(AVP)是体内一种重要内源性抗热物质.为此本实验观察了精氨酸加压素V1受体阻断剂(AVPV1阻断剂)对CHP引起的降温效应和发热效应的影响,旨在探讨CHP对体温影响是否与AVP有关.方法实验用SD大鼠分为4组,每组7只,即对照组、CHP组、AVPV1阻断剂组和CHP-AVPV1阻断剂组.用体温遥测系统测量大鼠的体温和活动的变化.给药途径和药物剂量分别给大鼠口饲CHP30mg/kg(30g/L玉米油)或玉米油1mL/kg后,立即腹腔注射AVPV1阻断剂20μg/kg(30mg/L生理盐水)或生理盐水1mL/kg.结果给大鼠口饲CHP后可以引起快速的降温效应,给药后5h后体温由给药前的(37.75±0.11)℃降低到(36.34±0.22)℃,平均降低达1.44℃;而给CHP后立即给AVPV1阻断剂时,大鼠体温由给药前的(37.55±0.17)℃降低到(37.19±0.14)℃,平均只降低了0.46℃.对照组动物在给药后,则出现短暂的应激性体温升高和活动增加现象.AVPV1阻断剂对CHP的发热相无明显影响.在实验中发现AVPV1阻断剂也可提高正常大鼠的体温,持续时间为2h.结论AVPV1阻断剂可以明显阻断CHP的降温效应,但对CHP的发热相无明显影响,提示AVP在CHP引起的降温过程中有重要作用.同时也证明内源性AVP在正常体温中可能有负调节作用.     

精氨酸加压素对大鼠下丘脑视前区AMPA受体GluR1-3蛋白表达的影响

目的研究精氨酸加压素(AVP)对大鼠下丘脑视前区(POA)α-氨基-3-羟基-5-甲基异恶唑-4-丙酸(AMPA)受体GluR1-3 mRNA和蛋白质表达的影响。方法腹腔注射AVP(10μg/kg)或AVP V1a受体抑制剂(30μg/kg)0.5 h后,用反转录实时荧光定量PCR和Western blot检测视前区AMPA受体亚基GluR1、GluR2和GluR3 mRNA和蛋白表达。结果与对照组相比,V1a受体抑制剂明显降低了GluR2 mRNA表达(P0.05);AVP能显著上调视前区AMPA受体亚基GluR1和GluR2蛋白水平(P0.01),减少GluR3蛋白表达(P0.01),但V1a受体抑制剂不能阻断这一作用。结论外源性AVP主要通过影响AMPA受体亚基蛋白表达来调制大鼠视前区AMPA受体介导的谷氨酸能突触传递。     

精氨酸加压素对大鼠视前区GABA_A受体亚单位磷酸化的影响

目的:研究精氨酸加压素(AVP)对大鼠视前区γ-氨基丁酸(GABA)A型受体(GABA_A受体)亚单位(α、β和γ2)表达和磷酸化的影响。方法:实验分为对照组、AVP组、V1a受体抑制剂+AVP组和V1a受体抑制剂组(均n=10);腹腔注射AVP或V1a受体抑制剂0.5 h后,采用RT-qPCR和Western blot法检测视前区GABA_A受体亚单位(α、β和γ2)表达及磷酸化的变化。结果:与对照组相比,AVP或V1a受体抑制剂组大鼠视前区GABA_A受体亚单位表达均无显著变化;AVP能显著上调视前区GABA_A受体γ2亚单位的磷酸化水平(P0.05);AVP显著增加蛋白激酶C(PKC)和钙/钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)表达和磷酸化(P0.01)。结论:外源性AVP不影响GABA_A受体亚单位(α、β和γ2)表达,但主要通过V1a受体激活PKC和CaMKⅡ,影响γ2亚单位磷酸化水平,从而调制视前区GABA_A受体介导的抑制性突触传递。     

胆碱能阻断剂对梭曼引起大鼠降温效应的影响

目的：本研究使用胆碱能阻断剂探讨梭曼引起降温作用的胆碱能途径。方法： 用数字体温计测量大鼠的结肠温度，每次间隔60 min, 观察了外周性毒蕈碱阻断剂甲基东莨菪碱和中枢性毒蕈碱阻断剂东莨菪碱对梭曼引起大鼠降温效应的影响。结果： 皮下注射梭曼(60 μg·kg^-1)后可引起体温快速的降低，腹腔注射东莨菪碱(1　mg·kg^-1)可明显阻断梭曼的降温作用，注射甲基东莨菪碱(1 mg·kg^-1)对其降温作用无明显影响。结论： 实验结果表明，梭曼引起的降温作用主要是通过中枢毒蕈碱型胆碱能通路所致。     

AVP V1受体阻断剂对昼光和暗光中正常大鼠体温的影响

目的: 研究内源性精氨酸加压素(AVP)是否参与正常的体温调节过程。方法: 用无线体温遥测仪测量大鼠的体温变化,观察腹腔注射AVPV₁受体阻断剂对昼光和暗光中(明∶暗=12∶12)大鼠体温的影响。结果: 腹腔注射AVPV₁受体阻断剂可明显提高大鼠的正常体温,在昼光中(6:00AM-6:00PM)体温升高持续的时间长达6h,雄性大鼠的体温明显高于雌性的体温。在暗光中(6:00PM-6:00AM),AVPV₁受体阻断剂只使进入暗光初期的大鼠体温升高,持续的时间为2h,雄性和雌性之间无明显差别。结论: AVPV₁受体阻断剂可使正常大鼠体温升高,实验结果提示内源性AVP对正常体温有紧张性调节作用。     

在冷环境中大鼠下丘脑TRPA1参与体温调节的作用

目的探讨冷环境中大鼠下丘脑TRPA1(transient receptor potential cation channel,subfamily A,member 1)对大鼠体温的调节作用。方法利用人工气候箱将大鼠暴露于不同冷环境温度中,观察其体温变化;预先在大鼠侧脑室内给予TRPA1特异性阻断剂HC030031后,在4℃冷环境温度下观察其体温的变化;采用Real Time PCR的方法检测了正常室温情况下大鼠下丘脑前部和后部组织TRPA1m RNA的表达水平。结果环境温度越低,大鼠体温降低越明显。侧脑室给予TRPA1的特异性阻断剂HC030031后,4℃环境温度下,体温下降明显,与室温对照组(N)及溶剂对照组(M)相比较,均有显著性差异(P0.01)。大鼠下丘脑后部组织TRPA1m RNA的表达量明显高于下丘脑前部组织。结论大鼠下丘脑中TRPA1通道蛋白参与了冷环境下对机体体温的调节。     

毒死蜱对大鼠的降温作用与尾部皮温变化的关系

目的 :有研究发现有机磷可以引起体温的变化 ,本实验观察了有机磷农药毒死蜱 (Ｃｈｌｏｒｐｙｒｉｆｏｓ)对大鼠体温的影响与尾部皮肤温度变化的关系。方法 :实验用 1 8只Ｌｏｎｇ -Ｅｖａｎｓ雌性大鼠 ,实验环境温度为 2 5～ 2 6℃。用智能多导测温仪 (上海医用仪表厂 )测量体内深部温度 ,用热电偶温度计测量尾部皮温。实验分两组 :1 对照组 (ｎ =9) :经口灌入玉米油 ,1ｍＬ/ｋｇ;2 实验组 (ｎ =9) :经口灌入毒死蜱 2 5ｍｇ/ｋｇ( 2 5ｍｇ/ｍＬ玉米油 )。每次实验先观察正常体温和尾温 1ｈ ,作为给药前的对照值 ,然后给玉米油或毒死蜱后 …     

The vasopressin receptor of the blood-brain barrier in the rat hippocampus is linked to calcium signalling.

The signal transduction system of the vasopressin receptor in cerebral microvessels is not known but appears not to be adenylate cyclase/cyclic AMP. We determined the effect of arginine vasopressin (AVP) on the intracellular free calcium concentration [Ca2+]i in endothelial cells of isolated hippocampal microvessels of rats, using the fura-2 fluorescence technique. AVP administration caused a rapid and transient rise of cytosolic free calcium which was absent after extracellular calcium was removed, and could be blocked with the vasopressin V1 receptor antagonist, d(CH2)5 Tyr(Me)AVP. The vasopressin V2 receptor agonist, 1-deamino-8,D-AVP, on the contrary, failed to affect the intracellular free calcium level, and was unable to inhibit the AVP-induced rise of [Ca2+]i in the preparation. Our results, therefore, demonstrate the presence of a calcium-signalling, i.e. V1 vasopressin receptor at the blood-brain barrier in the hippocampus of the rat.     

Grooming, body extension, and vasomotor responses induced by hypothalamic warming at different ambient temperatures in rats

During heat stress, rats extend their body and spread saliva onto their body surfaces (grooming) for evaporative heat loss in addition to tail vasodilation. We investigated the effects of changing hypothalamic (Thy) and ambient (Ta) temperatures on these thermoregulatory responses. The higher the Ta, the lower the Thy at which grooming started when Ta was changed from the thermoneutral zone (24 degrees C) to 28-40 degrees C. At any Ta grooming was induced only when the posterior hypothalamic region (PH) was warmed by implanted diathermy. Grooming was more strongly induced at a Ta of 28 degrees C than at 24 degrees C. At a Ta of 32 degrees C, PH warming evoked body extension as well, decreasing the duration of grooming as compared to that at 28 degrees C. Warming the preoptic area and anterior hypothalamus induced body extension and tail vasodilation regardless of Ta. The data suggest that grooming was induced by integrated temperature signals from the PH and from the peripheral skin.     

Effect of physical restraint on the limits of thermoregulation in telemetered rats

Physical restraint of rodents is needed for nose-only exposure to airborne toxicants and is also used as a means of psychological stress. Hyperthermia is often observed in restrained rats, presumably as a result of impairments in heat dissipation. However, such a hyperthermic response should be dependent on the prevailing ambient conditions. To understand how ambient temperature (T(a)) affects the thermoregulatory response to restraint, core temperature (T(c)) and heart rate (HR) were monitored by telemetry in rats subjected to 1 h of physical restraint while T(a) was maintained at 14-30 °C in 2 °C increments. The T(c) of unrestrained rats was unaffected by T(a). During restraint, T(c) was elevated at ambient temperatures with the exception of 14 °C, at which the rats became mildly hypothermic. There was an inverse relationship between T(a) and HR in both unrestrained and restrained rats; however, HR was significantly elevated in restrained rats at all ambient temperatures except 22 and 24 °C. Heat loss from the tail, estimated from T(c) and tail skin temperature, was markedly reduced at all but the highest ambient temperatures in restrained rats. The data suggest that the T(a) limits of normothermia are narrowed in the restrained rat. That is, between 16 and 20 °C, the rat maintains a relatively stable T(c) that is slightly elevated above that of the unrestrained rat. At ambient temperatures above or below this range, the rat shows signs of hyperthermia and hypothermia, respectively. In contrast, the limits of normothermia for unrestrained rats range from 14 (or lower) to 30 °C. Overall, the ideal T(a) for restrained rats appears to be 20 °C and no higher than 22 °C for the thermoregulatory system to maintain a regulated T(c) in rats well adapted to physical restraint.     

Serotoninergic mechanisms of beta-endorphin-induced hypothermia in rats

The effects of intraventricular administration of beta-endorphin on thermoregulatory responses of unanesthetized rats to different ambient temperatures (T _a ) of 8, 22 and 30°C were assessed. Administration of beta-endorphin produced a fall in rectal temperature at bothT _a 8 and 22°C. The hypothermia in response to beta-endorphin was brought about by both cutaneous vasodilation (as indicated by an increase in both the tail and the foot skin temperatures) and decreases in metabolic heat production. However, atT _a 30°C, administration of beta-endorphin produced no change in rectal temperature or other thermoregulatory responses. Furthermore, the hypothermic effect induced by beta-endorphin was greatly attenuated by either the depletion of brain serotonin levels (with 5,6-dihydroxytryptamine andp-chlorophenylanine) or the blockade of opiate receptors (with naloxone). The data indicate that beta-endorphin leads to hypothermia in rats by increasing sensible heat loss and decreasing metabolic heat production, probably via the release of endogenous serotonin within brain.     

Effects of sodium acetylsalicylate on thermoregulatory responses of rats to different ambient temperatures

The effects of intraperitoneal administration of sodium acetylsalicylate (aspirin) on thermoregulatory responses (T_a) of 15, 22 and 29°C were assessed. Intraperitoneal administration of aspirin produced dose-dependent hypothermia at both 15 and 22°C. The hypothermia was brought about by cutaneous vasodilation (as indicated by an increase of the tail and foot skin temperatures). However, in the heat (29°C), i. p. administration of the same amount of aspirin produced no change in rectal temperature, since the thermoregulatory responses were unaffected by aspirin application at this T_a. Thus it appears that aspirin increases heat loss and leads to hypothermia in rats.