肾脏去神经化在心力衰竭治疗中的研究进展

生理情况下,心脏和肾脏在血流动力学和神经激素等调节中相互作用,对于循环系统的稳态维持起重要作用。但在充血性心力衰竭的病理情况下,心脏和肾脏之间存在明显的调节紊乱。首先,急性失代偿性心力衰竭的患者住院治疗的研究结果证明其有一定程度的肾脏失调。其次,慢性充血性心力衰竭时肾脏交感神经系统也起到重要作用:肾脏交感纤维活性增强可导致肾素的释放、钠水潴留、肾血流的降低、血管阻力增加、左心室重塑、左心功能失调等。众所周知,肾脏交感神经切除术可以减低血压和改善心脏功能,但是由于有创的手术方式限制了其应用。过去两年间,随着新的导管消融肾脏去神经化技术的日益完善,其有望成为治疗高血压病和心力衰竭的手段。在此,本文综述了心力衰竭时肾脏交感传入神经和传出神经的发病机理,对目前进行的经导管肾脏去神经化治疗慢性心力衰竭的基础及临床试验进行安全性及有效性评价。提示我们经导管肾脏去神经化有望成为心力衰竭治疗的新靶点。     

神经系统与心律失常

焦虑、悲伤、情绪紧张等可使儿茶酚胺分泌过多、心电图出现 ST 段 T 波变化、心肌纤维断裂及各种室性心律失常.电刺激或将药物注入动物脑内不同部位可产生各种心律失常.在中脑中央灰质内注入微量去甲肾上腺素或乙酰胆硷均可增加刺激下丘脑引起的室性期前收缩.脑内吗啡样物质、5-羟色胺水平增加可降低交感中枢紧张性,导致交感神经传出冲动减少,降低心室易颤性,减少刺激下丘脑引起的室性期前收缩.躯体传入冲动对刺激下丘脑诱发期前收缩的抑制作用与脑内吗啡样物质的释放及下丘脑弓状核区、中脑中央灰质等处阿片受体的激活有关,且部分通过5-羟色胺途径.     

神经系统与心律失常

焦虑、悲伤、情绪紧张等可使儿茶酚胺分泌过多、心电图出现ST段T波变化、心肌纤维断裂及各种室性心律失常。电刺激或将药物注入动物脑内不同部位可产生各种心律失常。在中脑中央灰质内注入微量去甲肾上腺素或乙酰胆硷均可增加刺激下丘脑引起的室性期前收缩。脑内吗啡样物质、5-羟色胺水平增加可降低交感中枢紧张性,导致交感神经传出冲动减少,降低心室易颤性,减少刺激下丘脑引起的室性期前收缩。躯体传入冲动对刺激下丘脑诱发期前收缩的抑制作用与脑内吗啡样物质的释放及下丘脑弓状核区、中脑中央灰质等处阿片受体的激活有关,且部分通过5-羟色胺途径。     

脂联素通过激活PPARα减轻血管紧张素Ⅱ诱导的心肌纤维化

脂联素（adiponectin）是主要由白色脂肪组织分泌的肽类激素,具有调节糖脂代谢、抗炎、抗动脉粥样硬化等多种生物学作用。已有研究证实,脂联素对心肌缺血一再灌注损伤以及内皮素-1、α-去甲肾上腺素引起的心肌肥大具有明显的改善作用。心肌纤维化是心室重塑及慢性心衰进行性发展的重要机制之一,但目前脂联素对心肌纤维化的影响还不明确。     

Catestatin——新的心血管保护肽

Catestatin是一种新的心血管保护肽由嗜铬蛋白A(CHGA)剪切产生,在肾上腺嗜铬细胞、肾上腺素能神经元及心肌内表达,通过自分泌/旁分泌的方式发挥多种心血管保护效应。Catestatin可负反馈调节儿茶酚胺释放、促进肥大细胞脱颗粒、调节自主神经系统功能,进而舒张血管、拮抗高血压病的发生;通过促进内皮细胞释放碱性成纤维细胞生长因子、激活丝裂原蛋白激酶(MAPK)信息传导途径促进血管新生。Catestatin也可激活磷酸肌醇-3激酶/蛋白激酶B(PI3K/Akt)信号传导途径拮抗心肌缺血再灌注损伤;或通过反向激动心肌β受体等多种机制,延缓充血性心力衰竭病程。     

内源性可乐宁样物质

可乐宁(clonidine)是一种人工合成的α_2受体激动剂,可抑制中枢交感神经的传出冲动,产生强大的降压效应,已被广泛应用于临床各型高血压的治疗。去甲肾上腺素和α-甲基多巴也是中枢α受体特异性配基;它们的作用与可乐宁不同。例如,网状外侧核内注射微量可乐宁,可引起明显的降压作用;但注射去甲肾上腺素或α-甲基多巴则不能引起。去     

蛙眼的瞳孔调节实验

1　原理蛙眼瞳孔大小的变化是受植物性神经和体液调节的。支配虹膜的交感神经节后纤维通过释放去甲肾上腺素作用于瞳孔散大肌 ,其收缩时使瞳孔变大。而肾上腺髓质的主要产物肾上腺素也具有同样的作用效果。商品肾上腺素药物中包含肾上腺素和去甲肾上腺素两种物质。动眼神经中的副交感神经节后纤维通过释放乙酰胆碱递质作用于瞳孔括约肌 ,其收缩时使瞳孔变小。阿托品可以阻断 M型毒蕈碱型乙酰胆碱受体 ,从而使乙酰胆碱不能发挥作用。2　材料　　活蛙、解剖皿、表玻璃皿 2个、0 .1%乙酰胆碱1mg/ml、0 .0 1%肾上腺素 0 .1mg/ml、任氏液、1%阿…     

脑室注射高低渗NaCl溶液对血浆肾素活性及肾交感神经活动的影响

第三脑室注射高渗NaCl溶液可引起肾交感神经活动(RSNA)减弱和血浆肾素活性(PRA)降低,低渗NaCl的作用则相反,引起KSNA及PRA升高。PRA和RSNA变化呈一定的正相关,切除肾神经后高、低渗NaCl对PRA的影响减弱或消失,表明脑室内Na~ 浓度改变后主要经肾交感神经的传出通路影响肾素释放。     

交感传出对多觉型伤害性感受器持续放电的易化效应

向大鼠皮肤感受野注射复合致痛剂使多觉型伤害性感受器产生持续放电。刺激支配感受野的交感神经可使单位持续放电显著增多,部分单位为先易化后抑制。这种易化效应时程较长,可以反复激发。局部动脉注射去甲肾上腺素(5μg/0.2ml)也可引起类似的效应。结果证实交感神经传出活动能够易化多觉型伤害性感受器的持续放电。讨论了不同实验结果和产生烧灼痛的可能原因。     

β-肾上腺素受体与乳腺癌相关性的研究进展

精神和情绪对于肿瘤的发生、发展具有重要作用.通常,在急性或慢性应激状态下,由交感神经系统介导的正常生理应激机制导致神经递质肾上腺素和去甲肾上腺素释放增多.对于恶性肿瘤患者,大量研究证实交感神经系统主要通过β-肾上腺素能受体途径介导的信号传导通路对肿瘤的进展和转移产生影响.乳腺癌患者多伴有焦虑预后不良而引起肾上腺素及去甲...     

Investigation of the mechanism of temperature sensitivity of the electroreceptors of ampullae of lorenzini

In experiments on Black Sea skates (Raja clavata), the potential of the receptor epithelium of the ampullae of Lorenzini and spike activity of single nerve fibers connected to them were investigated during electrical and temperature stimulation. Usually the potential within the canal was between 0 and –2 mV, and the input resistance of the ampulla 250–400 k. Heating of the region of the receptor epithelium was accompanied by a negative wave of potential, an increase in input resistance, and inhibition of spike activity. With worsening of the animal's condition the transepithelial potential became positive (up to +10 mV) but the input resistance of the ampulla during stimulation with a positive current was nonlinear in some cases: a regenerative spike of positive polarity appeared in the channel. During heating, the spike response was sometimes reversed in sign. It is suggested that fluctuations of the transepithelial potential and spike responses to temperature stimulation reflect changes in the potential difference on the basal membrane of the receptor cells, which is described by a relationship of the Nernst's or Goldman's equation type.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. I. M. Sechenov, Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Pacific Institute of Oceanology, Far Eastern Scientific Center, Academy of Sciences of the USSR, Vladivostok. Translated from Neirofiziologiya, Vol. 12, No. 1, pp. 67–74, January–February, 1980.     

Principles of organization and evolution of systems of regulation of functions

Evolution of living organisms is closely connected with evolution of structure of the system of regulations and its mechanisms. The functional ground of regulations is chemical signalization. As early as in unicellular organisms there is a set of signal mechanisms providing their life activity and orientation in space and time. Subsequent evolution of ways of chemical signalization followed the way of development of delivery pathways of chemical signal and development of mechanisms of its regulation. The mechanism of chemical regulation of the signal interaction is discussed by the example of the specialized system of transduction of signal from neuron to neuron, of effect of hormone on the epithelial cell and modulation of this effect. These mechanisms are considered as the most important ways of the fine and precise adaptation of chemical signalization underlying functioning of physiological systems and organs of the living organism