orexin-A对大鼠血压及血浆促肾上腺皮质激素和皮质酮浓度的影响
摘要
前言:应激反应引起的生理变化包括自主神经活动和神经内分泌活动的改变,以下丘脑-垂体-肾上腺皮质(HPA)轴激活及由此引起糖皮质类固醇(GC)分泌增加为重要特征。下丘脑作为重要的神经内分泌和自主神经活动调节中枢,通过整合体内外应激刺激引起的内分泌和自主神经活动改变,在维持内环境稳态和机体适应性反应中发挥着重要作用。Orexin是一类在下丘脑外侧区(lateralhypotahalmic area,LHA)和穹窿周区新发现的神经肽,包括orexin-A和orexin-B两种高度同源的肽。Orexin受体有orexin-1受体(orexin type 1 receptor,OX1R)和orexin-2受体(orexin type 2 receptor,OX2R)两种,它们均属于G蛋白偶联受体(G protein-coupled receptor,GPCR)家族。orexin神经元位于下丘脑外侧区和穹窿周区,其纤维却广泛投射于整个中枢神经系统,参与不同生理功能的调节和整合,目前已知其参与调节的生理活动包括摄食、消化、能量代谢平衡、睡眠/觉醒周期、药物依赖等。Orexin神经元对下丘脑室旁核(paraventricularhypothalamic nucleus,PVN)及其他自主神经和内分泌活动调节中枢的投射愈来愈受到人们的重视。并且,多项实验证据表明Orexin可能作为神经调质参与机体的应激反应。我们假设Orexin-A可能参与应激引起的大鼠心血管反应和垂体-肾上腺轴活动的改变
目的:观察侧脑室注射orexin-A对清醒大鼠尾动脉收缩压(tail arterialsystolic blood pressure,TBP)及垂体-肾上腺轴的影响。
方法:健康雄性成年Sprague-Dawley大鼠10只,随机分为两组,无菌手术建立侧脑室插管,恢复10天后,一组注射10μg orexin-A(溶于5μ1生理盐水),另一组注射5μ1生理盐水作为对照。使用无创尾动脉血压测量系统测量侧脑室注射前10分钟及注射后30分钟内TBP变化,测量完毕后迅速处死大鼠低温离心取血浆-80℃保存,采用酶联免疫吸附测定(enzyme-linked immunosorbantassay,ELISA)方法分析大鼠血浆促肾上腺皮质激素(adrenocorticotropichormone,ACTH)和皮质酮浓度。
结果:1.侧脑室注射10μg orexin-A可显著升高大鼠TBP,注射前10分钟TBP为117±2.5mmHg,注射后10分钟、20分钟和30分钟TBP分别升至136±6.1mmHg、1344±5.3mmHg和130±3.4mmng(P＜0.01)。2.与侧脑室注射生理盐水相比较,侧脑室注射orexin-A可显著增加大鼠血浆ACTH(P＜0.01)和皮质酮(P＜0.01)浓度。
结论:侧脑室注射orexin-A可增加大鼠TBP,增加血浆ACTH和皮质酮水平。
BACKGROUND: The hypothalamus is considered as an important organ which plays a pivotal role in the integration of a variety of neuroendocrine and autonomic response via a number of neurotransmitters upon challenges from external or internal stressors. Orexins, which were isolated from the lateral hypothalamic area (LHA) and perifornical area, include the two highly homologous peptides, orexin-A and orexin-B, proteolytically derived from the same precursor protein. Simultaneously with the discovery of orexins, the endogenous receptors for the two ligands were also identified as orexin type 1 and 2 receptors (OX1Rs and OX2Rs, respectively), both of which are members of the family of seven transmembrane domain G protein-coupled receptors (GPCRs). The orexin-containing neurons, confined in the lateral hypothalamic and perifornical area, broadly project to multiple regions of the whole central nervous system, implying their important role in the cooperation and integration of various physiological functions, such as feeding, digestion, balance of energy metabolism, sleeping/wake cycle, drug addiction, and so on. These days, the projections of the orexin neurons to the paraventricular hypothalamic nucleus (PVN) and other autonomic and endocrine centers draw researchers' attention. Several lines of evidence support a role of the Orexin as modulators of the stress response. However, it is unknown whether orexin is involved in stress induced cardiovascular response via an increase in activity of pituitary-adrenal axis.
OBJETIVE: In the present study we examined the effects of icv administrated orexin-A on the tail arterial systolic blood pressure (TBP) and pituitary-adreanl axis of rats subjected stress stimulation.
METERIALS AND METHODS: Ten Sprague-Dawley rats were randomly divided into two groups and implanted with a chronic indwelling cannula under sterile surgery. After ten days of recovery, one group were icv adminstrated 10μg orexin-A disolved in 5μl sterile saline and the other 5μl sterile saline as control. TBP were measured by a tail-cuff sphygmonometer 10 minutes before icv injection and in the following 30 minutes after icv injection, following which rats were immediately killed by decapitation and trunk blood was collected and centrifuged at 4℃. Supernatant plasma was collected and stored at -80℃. The concentration of plasma adrenocorticotropic hormone (ACTH) and corticosterone was determined by enzyme-linked immunosorbant assay (ELISA).
RESULTS: 1. Compared with the values (117±2. 5mmHg) of TBP 10 minutes before icv injection, orexin-A significantly increased rat TBP and the values at 10, 20 and 30 minutes after icv injection were 136±6.1mmHg、134±5.3mmHg和130±3.4mmHg (P<0.01) , respectively. 2. Compared with rats administrated with rats, orexin-A significantly increased plasma adrenocorticotropic hormone (ACTH) (P <0.01) and gluococorticosterone (P <0.01) concerntration.
CONCLUSIONS: Centrally administrated orexin-A increases rat TBP and the levels of plasma ACTH and corticosterone.
目的:观察侧脑室注射orexin-A对清醒大鼠尾动脉收缩压(tail arterialsystolic blood pressure,TBP)及垂体-肾上腺轴的影响。
方法:健康雄性成年Sprague-Dawley大鼠10只,随机分为两组,无菌手术建立侧脑室插管,恢复10天后,一组注射10μg orexin-A(溶于5μ1生理盐水),另一组注射5μ1生理盐水作为对照。使用无创尾动脉血压测量系统测量侧脑室注射前10分钟及注射后30分钟内TBP变化,测量完毕后迅速处死大鼠低温离心取血浆-80℃保存,采用酶联免疫吸附测定(enzyme-linked immunosorbantassay,ELISA)方法分析大鼠血浆促肾上腺皮质激素(adrenocorticotropichormone,ACTH)和皮质酮浓度。
结果:1.侧脑室注射10μg orexin-A可显著升高大鼠TBP,注射前10分钟TBP为117±2.5mmHg,注射后10分钟、20分钟和30分钟TBP分别升至136±6.1mmHg、1344±5.3mmHg和130±3.4mmng(P＜0.01)。2.与侧脑室注射生理盐水相比较,侧脑室注射orexin-A可显著增加大鼠血浆ACTH(P＜0.01)和皮质酮(P＜0.01)浓度。
结论:侧脑室注射orexin-A可增加大鼠TBP,增加血浆ACTH和皮质酮水平。
BACKGROUND: The hypothalamus is considered as an important organ which plays a pivotal role in the integration of a variety of neuroendocrine and autonomic response via a number of neurotransmitters upon challenges from external or internal stressors. Orexins, which were isolated from the lateral hypothalamic area (LHA) and perifornical area, include the two highly homologous peptides, orexin-A and orexin-B, proteolytically derived from the same precursor protein. Simultaneously with the discovery of orexins, the endogenous receptors for the two ligands were also identified as orexin type 1 and 2 receptors (OX1Rs and OX2Rs, respectively), both of which are members of the family of seven transmembrane domain G protein-coupled receptors (GPCRs). The orexin-containing neurons, confined in the lateral hypothalamic and perifornical area, broadly project to multiple regions of the whole central nervous system, implying their important role in the cooperation and integration of various physiological functions, such as feeding, digestion, balance of energy metabolism, sleeping/wake cycle, drug addiction, and so on. These days, the projections of the orexin neurons to the paraventricular hypothalamic nucleus (PVN) and other autonomic and endocrine centers draw researchers' attention. Several lines of evidence support a role of the Orexin as modulators of the stress response. However, it is unknown whether orexin is involved in stress induced cardiovascular response via an increase in activity of pituitary-adrenal axis.
OBJETIVE: In the present study we examined the effects of icv administrated orexin-A on the tail arterial systolic blood pressure (TBP) and pituitary-adreanl axis of rats subjected stress stimulation.
METERIALS AND METHODS: Ten Sprague-Dawley rats were randomly divided into two groups and implanted with a chronic indwelling cannula under sterile surgery. After ten days of recovery, one group were icv adminstrated 10μg orexin-A disolved in 5μl sterile saline and the other 5μl sterile saline as control. TBP were measured by a tail-cuff sphygmonometer 10 minutes before icv injection and in the following 30 minutes after icv injection, following which rats were immediately killed by decapitation and trunk blood was collected and centrifuged at 4℃. Supernatant plasma was collected and stored at -80℃. The concentration of plasma adrenocorticotropic hormone (ACTH) and corticosterone was determined by enzyme-linked immunosorbant assay (ELISA).
RESULTS: 1. Compared with the values (117±2. 5mmHg) of TBP 10 minutes before icv injection, orexin-A significantly increased rat TBP and the values at 10, 20 and 30 minutes after icv injection were 136±6.1mmHg、134±5.3mmHg和130±3.4mmHg (P<0.01) , respectively. 2. Compared with rats administrated with rats, orexin-A significantly increased plasma adrenocorticotropic hormone (ACTH) (P <0.01) and gluococorticosterone (P <0.01) concerntration.
CONCLUSIONS: Centrally administrated orexin-A increases rat TBP and the levels of plasma ACTH and corticosterone.
引文
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