延髓腹外侧头端微量注射尾加压素Ⅱ对麻醉大鼠血压、心率和肾神经放电活动的影响

发布时间：2018-03-24 10:28

  本文选题：尾加压素Ⅱ　切入点：延髓腹外侧头端　出处：《河北医科大学》2008年硕士论文

【摘要】： 尾加压素Ⅱ(urotensinⅡ, UⅡ)最早是从硬骨鱼的脊髓尾部垂体中分离出的生长抑素样环肽,后来证实从软体动物到哺乳动物体内均有存在。UⅡ及其受体GPR14(G-protein coupled receptor,GPR14)主要分布于中枢神经系统、心血管系统、肾脏和内分泌器官等。UⅡ与GPR14结合后使细胞内的Ca2+浓度增加,引起一系列生物效应。 UⅡ是迄今为止最强的缩血管活性肽,其缩血管作用是内皮素的10倍以上,具有种属特异性和组织特异性,且不需要内皮介导。UⅡ能促进大鼠胸主动脉摄取钙,这种作用能被钙通道阻断剂维拉帕米和尼群地平阻断,推测UⅡ通过电压依赖性和非电压依赖性钙通道促进钙内流。我们先前的研究表明UⅡ还可以抑制颈动脉窦压力感受器反射,此作用是UⅡ与平滑肌上的UⅡ受体结合,通过开放L型钙通道引起颈动脉窦区血管收缩而实现的。UⅡ还有舒张血管的效应,并呈内皮依赖性。UⅡ的舒血管效应可能与NO、前列环素等舒血管活性因子有关。UⅡ与冠心病的关系也很密切,急性冠脉综合症患者血浆中UⅡ的浓度明显下降,提示UⅡmRNA表达下调。UⅡ还有促进心肌肥大、刺激细胞外基质生成和介导粥样硬化斑块形成等效应。 对于UⅡ中枢效应的研究发现,给清醒的羊侧脑室注射UⅡ,引起血浆肾上腺素和促肾上腺皮质激素的释放,并使心输出量增大、血压升高。给清醒的鳟鱼脑室注射50pmol UⅡ仅引起轻度的心率增加,当剂量达到500pmol时引起血压显著升高而心率不变。在正常大鼠和高血压清醒大鼠,侧脑室注射UⅡ引起血压和心率显著增加,高血压大鼠尤为明显。UⅡ的作用因给药途径不同而不同:静脉注射UⅡ引起血压下降,而侧脑室注射UⅡ则因激活了交感神经系统而使血压上升。在不同脑区微量注射UⅡ,产生不同的心血管效应:在A1区微量注射UⅡ可引起剂量依赖性的和长时程的血压降低及心率减慢效应;而在A2区则没有明显效果;在室旁核和弓状核引起轻微但显著的血压升高和心动过速的效应。以上结果不仅说明,UⅡ在不同的脑区发挥不同的心血管作用,而且支持一种假设,即UⅡ在不同脑区的神经元中发挥不同作用。我们新近的研究表明,UⅡ能够抑制海马CA1区神经元、PVN神经元的自发放电;给大鼠的侧脑室注射UⅡ,20min后可在PVN神经元发现c-fos蛋白mRNA水平显著增加。 延髓腹外侧头端区(RVLM)接受来自中枢其它部位和外周传入的多种心血管活动信息,并有下行通路直接投射到胸段脊髓灰质中间外侧柱的交感节前神经元,从而在维持交感紧张和稳定血压的调节活动中具有重要意义。RVLM存在UⅡ受体GPR14的mRNA和蛋白表达,表明UⅡ及其受体GPR14在RVLM内可能具有调节心血管活动的功能。 目的:本研究旨在应用心血管中枢RVLM区微量注射的方法观察UⅡ对于大鼠心血管系统及肾交感神经放电活动的影响,探讨UⅡ及受体GPR14的生理作用及其信号传导机制。 方法:在36只麻醉雄性SD大鼠,将UⅡ微量注入RVLM区后,应用连接到计算机上的BL~420E+多道生物机能系统同步记录大鼠血压(BP)、心率(HR)和肾交感神经活动(RSNA)的原始放电和积分值。 结果:(1)UⅡ(0.3, 3 and 30 nmol/L)可使大鼠BP、HR和RSNA明显增加。与对照相比,BP(MAP)分别从86.12±4.66mmHg升高到99.42±3.85mmHg(P0.01), 86.67±4.41mmHg升高到98.92±4.20mmHg (P0.01),以及86.65±6.39mmHg升高到101.89±6.34 mmHg (P0.01);HR从322.80±9.37bpm升高到342.60±7.97bpm (P0.05), 325.33±5.27bpm升高到351.50±7.53bpm (P0.05),以及311.00±10.96bpm升高到338.33±11.56bpm (P0.01);RSNA分别兴奋了141.93±6.74% (P0.01), 133.96±6.88% (P0.01)和142.78±9.94% (P0.01)。BP、HR和RSNA在给药后15分钟内开始变化,在30~40分钟达到最高点(。2)预先向大鼠RVLM区微量注射UⅡ受体GPR14的阻断剂BIM23127 (300nmol/L),可以阻断UⅡ的作用。(3)预先向大鼠RVLM区微量注射N型Ca2+通道阻断剂芋螺毒素ω-conotoxin GVIA (200nmol/L),可以阻断UⅡ的作用。(4)预先向大鼠RVLM区微量注射丝裂原活化蛋白激酶(MAPK)激酶抑制剂PD98059(25μmol/L),可以抑制UⅡ的作用。 结论:在RVLM区内微量注射UⅡ使麻醉大鼠的血压、心率和肾交感神经放电活动明显增加。其机制可能为UⅡ与其受体GPR14结合,激活N型Ca2+通道,增强Ca2+内流进而激活MAPK途径而发挥作用。
[Abstract]:Urotensin II (urotensin II, U II) was first isolated from the tail of the spinal cord in the teleost pituitary somatostatin peptide that later confirmed from animal to mammals and there were software.U II and its receptor GPR14 (G-protein coupled receptor, GPR14) mainly distributed in the central nervous system and cardiovascular system. The kidney and endocrine organs such as.U II and GPR14 bind to the intracellular Ca2+ concentration increases, causing a series of biological effects.
U II is by far the strongest vasoactive peptide, the vasoconstrictive effect is 10 times more than in the endothelium, species-specific and tissue-specific, and does not need the endothelium mediated.U II can promote rat aortic calcium intake, and this effect can be calcium channel blocker nitrendipine block and Vera Pammy presumably, U II through voltage dependent and voltage dependent calcium channels to promote calcium influx. Our previous studies have shown that U II can also inhibit the carotid sinus baroreceptor reflex, this role is combined with U II and U II receptor on smooth muscle, caused by carotid sinus vasoconstriction achieved by open type L calcium channel.U II vasodilatation and effect, and is NO and endothelium-dependent vasodilation effects of.U II, the relationship between prostacyclin and other vasoactive factors associated with coronary heart disease.U II is also very close, in patients with acute coronary syndrome The concentration of U II decreased significantly, suggesting that U II mRNA expression was down regulated..U II also promoted myocardial hypertrophy, stimulated extracellular matrix production and mediate atherosclerotic plaque formation.
For the study of U II central effects found for sheep intracerebroventricular injection of U II awake, caused by plasma adrenaline and ACTH release, and increased cardiac output, increased blood pressure. To clear the trout intraventricular injection of 50pmol U II caused only slight increase in heart rate, when the dosage of 500pmol was caused by blood pressure increased heart rate unchanged. Awake rats in normal rats and hypertension, intracerebroventricular injection of U II induced blood pressure and heart rate increased significantly, especially in hypertensive rats.U II effect due to different routes of administration of intravenous injection of U II induced decrease in blood pressure, and intracerebroventricular injection of U II due to activation of the sympathetic the nervous system and blood pressure to rise. In different brain regions of microinjection of U II, produced varying cardiovascular effects in A1 microinjection of U II can induce dose dependent and duration to reduce blood pressure and heart rate effect; and There is no obvious effect in the A2 region; in the paraventricular and arcuate nuclei caused a slight but significant increase in blood pressure and tachycardia effect. These results not only illustrate that U II play different cardiovascular effects in different brain regions, but also support a hypothesis that U II in different brain regions of neurons we play a different role. Recent studies show that U II can inhibit hippocampal CA1 neurons, the spontaneous discharge of PVN neurons; to the intracerebroventricular injection of U of rats, after 20min PVN neurons found c-fos protein level of mRNA was significantly increased.
The rostral ventrolateral medulla (RVLM) from other parts of the central and peripheral afferent cardiovascular activities of various kinds of information, and the descending pathway directly onto the thoracic spinal cord intermediolateral column of sympathetic preganglionic neurons, which has the important significance of.RVLM mRNA and protein expression of U II receptor GPR14 in regulating sympathetic nervous activity to maintain the blood pressure and stability, show that U II and its receptor GPR14 may regulate the function of cardiovascular activity in RVLM.
Objective: the aim of this study is to observe the effects of U II on the cardiovascular system and renal sympathetic nerve activity in rats, and to explore the physiological function and signal transduction mechanism of U II and GPR14 receptor by using microinjection in the central area of RVLM.
Methods: in 36 anesthetized male SD rats, after injecting U II into RVLM area, we recorded the blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) of the original discharge and integral value by BL~420E+ multichannel biological function system connected to the computer.
缁撴灉:(1)U鈪，

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