延髓头端腹外侧区一氧化氮与慢性心力衰竭大鼠心交感传入反射物的关系

为观察延髓头端腹外侧区(rostral ventrolateral medulla,RVLM)一氧化氮(N0)在慢性心力衰竭(chronic heart failure,CHF)大鼠增强的心交感传入反射(cardiac sympathetic afferent reflex,CSAR)中的作用,实验在去压力感受器神经支配的结扎冠状动脉诱发的CHF大鼠和假手术SD大鼠进行,记录电刺激心交感传入神经中枢端前后的血压和肾交感神经活动(renal sympathetic nerve activity,RSNA)变化以评价CSAR。结果显示：(1)CHF大鼠的CSAR显著增强;(2)RVLM微量注射NO合酶(NOS)抑制剂MeTC增强对照组大鼠的CSAR但对CHF大鼠的CSAR无显著影响;(3)RVLM微量注射NO供体S-nitroso-N-acetyl-penicillamine(SNAP)抑制CHF大鼠增强的CSAR;(4)S-methyl-L-thioeitruline（MeTC)仅增强对照组大鼠基础水平的RSNA,而SNAP抑制对照组和CHF大鼠基础水平的RSNA。结果表明RVLM中内源性NO的减少是导致CHF大鼠CSAR增强的重要机制之一。     

延髓头端腹外侧区一氧化氮与慢性心力衰竭大鼠心交感传入反射的关系

为观察延髓头端腹外侧区(rostral ventrolateral medulla,RVLM)一氧化氮(NO)在慢性心力衰竭(chronic heartfailure,CHF)大鼠增强的心交感传入反射(cardiac sympathetic afferent reflex,CSAR)中的作用,实验在去压力感受器神经支配的结扎冠状动脉诱发的CHF大鼠和假手术SD大鼠进行,记录电刺激心交感传入神经中枢端前后的血压和肾交感神经活动(renal sympathetic nerve activity,RSNA)变化以评价CSAR.结果显示:(1)CHF大鼠的CSAR显著增强;(2)RVLM微量注射NO合酶(NOS)抑制剂MeTC增强对照组大鼠的CSAR但对CHF大鼠的CSAR无显著影响;(3)RVLM微量注射NO供体S-nitroso-N-acetyl-penicillamine(SNAP)抑制CHF大鼠增强的CSAR;(4)S-methyl-L-thiocitmline(MeTC)仅增强对照组大鼠基础水平的RSNA,而SNAP抑制对照组和CHF大鼠基础水平的RSNA.结果表明RVLM中内源性NO的减少是导致CHF大鼠CSAR增强的重要机制之.     

刺激外周傳入神經对交感傳出冲动节律的影响

颈上交感神经与内脏神经的传出冲动表现同相变化,冲动群互相同步,冲动的幅度与频率变化和动脉血压的变化相呼应,但内脏神经对传入刺激的反应较之颈上交感神经更为明显。以单个电刺激作用于迷走或颈动脉窦神经向中端,可诱发交感传出冲动呈兴奋——抑制双相反应。如给予重复电刺激,交感冲动群发放的频率变成与刺激的频率同步,其最高频率可达每秒10—3次。更高频率时,不再表现规律性,转为连续的发放。停止刺激后,有后抑制现象。重复电刺激家兔减压神经或猫和兔的坐骨神经,能完全抑制交感神经干的冲动发放。同样,重复电刺激猫主动脉弓附近神经小枝时,引起交感干持续、强烈的冲动发放。如同时刺激猫的主动脉弓处神经小枝及坐骨神经,则在一定的刺激频率下,交感冲动亦与刺激同步,最高可达7—8次/秒。以重复电刺激直接作用于延髓加压区,可得到良好的交感传出冲动节律同步的反应。刺激闩都附近可完全抑制交感传出冲动,但长期刺激下,能在抑制下释放出来,表现与刺激节律同步的冲动发放,以上两种同步的最高频率亦可达10—13次/秒。在延髓以上水平切断脑干,不影响上述机能;在闩部前方切断脑干,交感冲动大部分消失,也不能再产生反射性变化。以上结果说明,在刺激迷走和窦神经时所引起的交感传出冲动群的节律性,乃由于此两种传入神经中含有抑制性和兴奋性两种纤维。在其影响下,中枢交替发生兴奋与抑制,从而反映于传出冲动。     

在不同的交感中枢活动水平时刺激腓深神经对肾神经发放的影响

本工作记录家免肾神经冲动和动脉血压,观察电刺激腓深神经的效应。在用减少通气量、切断双侧迷走神经、切断双侧缓冲神经等方法使交感中枢活动水平升高时,刺激腓深神经(3V、10Hz、0.3ms 持续15min)对血压无明显影响,但可以抑制肾神经的发放。相反,用过度通气或刺激一侧降压神经的方法使交感中枢活动水平降低时,同样的参数刺激腓深神经,则使肾神经发放增加。刺激腓深神经对肾神经发放的抑制效应,可为静脉注射纳洛酮阻断,而兴奋效应则被静脉注射东莨菪碱阻断。上述结果表明:低频低强度刺激腓深神经可引起肾神经发放的抑制或增强,其效应取决于交感中枢的活动状态。躯体传入对肾神经发放的抑制效应有内源性阿片样物质参与,而躯体传入对肾神经发放的兴奋效应则和中枢胆碱能系统的激活有关。     

电刺激延髓最后区对血浆肾素活性及肾交感神经活动的影响

实验在68只家兔上进行。乌拉坦麻醉。用RM-6000型多道仪同步记录呼吸(Respir)、血压(BP)、心率(HR)及肾神经放电(RSNA)。用放免法测定血浆肾素活性(PRA)。应用外径0.3mm的双芯同心电极置于延髓最后区(AP)处进行电刺激,每30s刺激4s。实验分为三组。第一组仅刺激AP观察到PRA增加了91％,RSNA出现以兴奋为主的三种放电形式,BP升高,HR减慢,呼吸无显著变化。第二组去除双侧肾神经后再刺激AP,PRA增加甚微,RSNA及血流动力学反应与第一组刺激前后的变化相似。第三组注射心得安后,刺激AP,这时除PRA明显抑制外,RSNA、BP、HR及呼吸亦与第一、第二组刺激前后的变化相似。上述结果表明电刺激兔AP能引起肾素释放增加,肾交感神经放电及血流动力学活动增强。     

伏核对心血管活动的作用及其与阿片肽的关系

本文对乌拉坦麻醉大鼠采用电刺激伏核和脑内微量注射等方法,观察伏核对血压、心率的影响:(1)电刺激伏核具有明显的血压降低和心率减慢作用。(2)红藻氨酸微量注入伏核可消除上述反应。(3)伏核内注射纳洛酮可阻断电刺激伏核的心血管抑制反应(简称电刺激效应);μ受体激动剂DAGO微量注入伏核也能引起血压降低和心率减慢,减少幅度与电刺激效应相似,而κ受体激动剂U-50无此作用。(4)电刺激伏核时于蓝斑内记录到抑制性自发电活动,频率减慢,波幅交大、变宽。(5)切除颈部双侧迷走神经消除了电刺激伏核的心率变化,但降压反应依然存在。以上结果提示:伏核内某些神经元与心血管活动有关,并且至少涉及阿片肽能神经元及μ阿片受体。蓝斑和迷走神经可能参与上述心血管抑制反应。     

刺激猫下丘脑LHA和VMN对小脑皮层神经元电活动的影响

在戊巴比妥钠麻醉的猫,电刺激下丘脑外侧区(LHA)和腹内侧核(VMN)可引起小脑皮层第Ⅵ和Ⅶ小叶浦肯野细胞和非浦肯野细胞抑制性、兴奋性和抑制-兴奋性的电活动,但以抑制性活动为主;这些反应的潜伏期多数为10-20ms,但也可长达90ms;一般刺激LHA比刺激VMN更有效。刺激下丘脑所激发的小脑神经元抑制性电活动可为静脉注射组胺H_1受体阻断剂扑尔敏所阻断。本文对上述观察的可能作用作了讨论。     

兔下丘脑室旁核刺激引起的肾交感神经传出活动的抑制

本实验用家兔,氯醛糖及尿酯混合静脉麻醉,制动,人工呼吸,颈部分离出三对神经——迷走、窦及主动脉神经,以备实验中切断。记录股动脉压、肾交感神经传出性放电活动(RSED)及其频率幅度直方图。借助脑立体定向仪刺激下丘脑室旁核,当刺激较强时,在交感神经放电短暂增加之后,可引起血压升高及RSED抑制。这一抑制过程可分为两个时相:血压不变期间的初期抑制时相及与血压升高同时并存的后期抑制时相。实验发现RSED总抑制时程及后期抑制时程均与血压变动具有正相关关系,而初期抑制时程与血压变动无相关关系。切断压力感受性神经前后,虽初期抑制时程的均值无显著差异,但在切断压力感受性神经后,总抑制时程及后期抑制时程的均值大大缩短。当用较弱刺激施于室旁核时,可不引起血压变化,但仍能引起RSED抑制。这个抑制亦可因切断压力感受神经而显著缩短。上述实验结果表明:(1) 在中枢内存在着一个室旁核-肾交感传出系统的抑制机制;(2) 初期抑制来源于中枢性抑制机制,而后期抑制时相主要来源于压力感受性反射,但亦有中枢抑制机制的参与;(3) RSED的中枢抑制可能并不是兴奋后压抑,而是自室旁核至脊髓交感节前神经元的主动性抑制。     

不同血压水平下刺激腓深神经对兔肾交感神经放电的影响

本实验观察了53例兔在不同血压水平下不同参数的腓深神经刺激对肾交感神经活动的影响。物在正常血压时,用低强度电流(3V,0.15—0.3mA,12Hz,0.5ms)刺激腓深神经可明显抑制肾交感冲动发放,静脉注射纳洛酮可以阻断此抑制效应;而用中等强度电流(10V,0.5—0.8mA)刺激腓深神经对肾交感活动没有明显抑制效应。当静脉匀速注射硝普钠使动物血压降低、肾交感冲动增加时,用中等强度刺激腓深神经可使肾交感冲动发放进一步增多,而用低强度刺激对肾交感活动无显著影响。静脉注射东莨菪碱(0.25mg/kg)可阻断低血压时刺激腓深神经引起的肾交感兴奋效应,但静脉注射纳洛酮(0.4mg/kg)却不能阻断。又当静脉匀速注射去甲肾上腺素造成动物较高血压时,肾交感冲动减少,用上述二种强度刺激腓深神经均使肾交感活动进一步受到明显抑制,此抑制效应可被静脉注射纳洛酮阻断,但不受东莨菪碱的影响。实验结果表明:刺激腓深神经引起的不同肾交感活动反应与所用刺激参数及动物血压水平和肾交感活动水平有关。刺激腓深神经引起的交感活动减弱或增强的反应,其神经机制可能不完全相同。前者可能有阿片受体的参与,而后者可能是胆碱能受体起着较重要的作用。     

刺激大鼠延髓腹面加压区对肾血管收缩活动的影响及其神经递质机制

实验在64只乌拉坦腹腔麻醉的大鼠身上进行。以电刺激(0.5ms,80—100Hz,10—30μA,40s)或L-谷氨酸(L-Glu)兴奋大鼠延髓腹面加压区(VSMp),肾交感神经电活动增强,肾血流阻力上升,与此同时血压上升。肾血流阻力的增加明显依赖于肾神经的完整性。非特异性α受体阻断剂酚妥拉明和特异性α_2受体阻断剂育亨宾阻断VSMP兴奋时增加肾血流阻力的作用并表现剂量依赖性关系,但特异性α_1-受体阻断剂哌唑嗪没有这种影响。特异性α_2-受体激动剂可乐宁灌流去神经肾血管表现与电刺激VSMp近似的结果。结果表明:VSMp兴奋时通过肾交感神经末梢释放以α_2受体为介导的儿茶酚氨类递质,影响肾血管的收缩活动。     

大鼠前庭内侧核在前庭—交感反应中的作用

实验在氯醛糖和尿酯混合麻醉的大鼠上进行。在内脏大神经上记录刺激同侧前庭神经进入脑干处的交感反应。电刺激前庭神经可在同侧内脏大神经引出—明确的叠加反应,其平均潜伏期为45.8±6.98ms,时程为55.21±5.35ms。增加刺激强度,反应幅度也增加,但潜伏期不变。用前庭内侧核(NVM)的片层场电位作为指标并选择其相位倒转处作刺激点,可在同侧内脏大神经记录到潜伏期为32ms 的叠加反应,而同一动物刺激前庭神经入脑处时内脏大神经反应的潜伏期为43ms。在 NVM 头端损毁后,此前庭-交感反应明显减小,再损毁尾端 NVM 后,此反应消失。损毁 Deiters 核对前庭-交感反应无影响。这些结果表明 NVM在内脏大神经记录到的前庭-交感反应中是一重要的中继站。     

Neural regulation of glucagon-like peptide-1 secretion in pigs

Glucagon-like peptide (GLP)-1 is secreted rapidly from the intestine postprandially. We therefore investigated its possible neural regulation. With the use of isolated perfused porcine ileum, GLP-1 secretion was measured in response to electrical stimulation of the mixed, perivascular nerve supply and infusions of neuroactive agents alone and in combination with different blocking agents. Electrical nerve stimulation inhibited GLP-1 secretion, an effect abolished by phentolamine. Norepinephrine inhibited secretion, and phentolamine abolished this effect. GLP-1 secretion was stimulated by isoproterenol (abolished by propranolol). Acetylcholine stimulated GLP-1 secretion, and atropine blocked this effect. Dimethylphenylpiperazine stimulated GLP-1 secretion. In chloralose-anesthetized pigs, however, electrical stimulation of the vagal trunks at the level of the diaphragm had no effect on GLP-1 or GLP-2 and weak effects on glucose-dependent insulinotropic peptide and somatostatin secretion, although this elicited a marked atropine-resistant release of the neuropeptide vasoactive intestinal polypeptide to the portal circulation. Thus GLP-1 secretion is inhibited by the sympathetic nerves to the gut and may be stimulated by intrinsic cholinergic nerves, whereas the extrinsic vagal supply has no effect.     

中缝背核参与下丘脑弓状核对蓝斑伤害性反应的抑制

实验在56只水合氯醛麻醉的成年雄性大鼠上进行。实验结果表明:电刺激中缝背核(DR)能减慢蓝斑(LC)大多数神经元自发放电频率;而损毁DR则增加大多数LC神经元的自发放电频率。电刺激下丘脑弓状核(ARC)能抑制LC神经元对外周坐骨神经伤害性刺激的反应。刺激DR可增强此种抑制作用;相反,损毁DR能部分减弱此种抑制效应。结果提示,DR对LC神经元有紧张性抑制作用,并对刺激ARC抑制LC神经元伤害性反应起着调制作用。     

急性神经损伤引起脊髓背角C-纤维诱发电位长时程增强

神经损伤引起神经病性疼痛,表现为持续性痛超敏和痛觉过敏。目前对神经病性疼痛的机制尚缺乏了解。我们以往的工作表明强直电刺激坐骨神经可引起脊髓背角C-纤维诱发电位的长时程增强(long-term potentiation,LTP),该LTP被认为是病理性疼痛的突触模型。本研究的目的在于探讨急性神经损伤是否能在完整动物的脊髓背角诱发出C-纤维诱发电位LTP。在以测试刺激(10～20V,0．5ms)电刺激坐骨神经的同时在脊髓背角用微电极记录C一纤维诱发电位。分别用强直刺激、剪断或夹捏坐骨神经诱导LTP。结果发现：(1)剪断或夹捏坐骨神经都可以诱导脊髓背角C-纤维诱发电位的LTP,该LTP可持续到实验结束(3～9h),在剪断神经前10min用利多卡因局部阻滞坐骨神经则可完全阻断LTP的产生;(2)神经损伤诱导的LTP可被NMDA受体阻断剂AP5所阻断;(3)用单次强直刺激引起LTP后,切断坐骨神经可使LTP的幅度进一步增大,而用多次强直电刺激使LTP饱和后,损伤神经则不能使LTP进一步增大。切断神经引起LTP后,强直电刺激也不能使LTP进一步增大。这些结果表明,急性神经损伤可以诱导脊髓背角C纤维诱发电位LTP,且切断神经能更有效地诱导LTP。该试验进一步支持我们的设想,即脊髓背角C-纤维诱发电位LTP可能在病理性疼痛的形成中起重要作用。     

Slow potentials in taste cells induced by frog glossopharyngeal nerve stimulation

Intracellular recordings were made from the taste cells of atropinized bullfrogs while the glossopharyngeal (GP) nerve fibres were electrically stimulated. Two types of slow potential, slow hyperpolarizing potentials (HPs) and slow depolarizing potentials (DPs), were induced in the taste cells. The slow HPs appeared when the lingual capillary blood flow was kept above 0.7 mm/s, whereas the slow DPs appeared when the blood flow was slowed down below 0.7 mm/s. The membrane resistance of a taste cell increased during the generation of a slow HP, but decreased during the generation of a slow DP. The reversal potentials for the slow HPs and the slow DPs were recorded at the same membrane potential (-11 to approximately -13 mV). Activation of non-selective cation channels possibly induced the slow DP and inactivation of those channels possibly induced the slow HP in the taste cell membrane. Electrical stimulation of the GP nerve activated a population of C fibres in the nerve and possibly released neurotransmitters from the nerve terminals. Released neurotransmitters might cause modulation of the membrane conductance in taste cells that leads to generation of the slow potentials. The present data suggest that slow HPs and slow DPs evoked in the taste cells of atropinized frogs by GP nerve stimulation are induced by putative neurotransmitters in the taste disc.     

刺激兔下丘脑室旁核诱发的心律失常与增压反应

在60只局麻与肌松剂制动的家兔,观察到用0.1—0.4mA,50Hz,1ms 的方波电刺激下丘脑室旁核(PV)能诱发频发性心律失常(包括室性与室上性期前收缩)及显著的动脉血压升高。与同侧的下丘脑外侧区(LHA)及腹内侧核(VMH)相比,刺激PV诱发期前收缩的次数更为频繁,增压反应幅度较大,且所需阈值亦较低。较低强度刺激LHA 在部分兔能引起血压下降与心率减慢,而PV 则一致地诱发增压反应。电刺激腓深神经能抑制刺激PV诱发的期前收缩,但在中脑中央灰质微量注射吗啡或电解毁损只能完全阻断刺激VMH诱发的期前收缩,而不能完全阻断PV诱发的期前收缩。这些结果提示,PV是下丘脑中诱发心律失常与血压增高的高反应区之一,并且可能具有不同于LHA或VMH的神经机制或下行神经通路。     

Control of glucose balance in the perfused rat liver by the parasympathetic innervation

Electrical stimulation of the nerve bundles around the hepatic artery and the portal vein activates both the sympathetic and parasympathetic liver nerves; the sympathetic effects clearly predominate. Parasympathetic effects were therefore studied in the rat liver perfused in situ by perivascular nerve stimulation in the presence of both an alpha- and a beta-blocker. In the presence of the alpha-blocker phentolamine and the beta-blocker propranolol all sympathetic nerve effects were prevented; the remaining parasympathetic stimulation had no influence on the basal glucose and lactate metabolism nor on the hemodynamics. Insulin alone, with both alpha- and beta-blockade, provoked a small, parasympathetic nerve stimulation in the presence of insulin a more pronounced enhancement of glucose utilization. In the presence of an alpha- and beta-blocker perivascular nerve stimulation antagonized the glucagon stimulated glucose release, but did not affect lactate exchange. The nerve effect was abolished by the parasympathetic antagonist atropine. Acetylcholine or insulin, with both an alpha- and beta-blocker present, mimicked the effects of nerve stimulation antagonizing the glucagon-stimulated glucose release. Nerve stimulation in the presence of insulin was more effective than either stimulus alone. The present results show that in rat liver stimulation of the parasympathetic hepatic nerves has direct effects on glucose metabolism synergistic with insulin and antagonistic to glucagon.     

COMPARISON OF THE EFFECT OF DIFFERENT SHORT CHAIN FATTY ACIDS ON THE GROWTH AND DIFFERENTIATION OF HUMAN COLONIC CARCINOMA CELL LINESIN VITRO

The aim of this study was to compare the effects of acetate, propionate, butyrate, iso-butyrate, valerate, iso-valerate and caproate on cell growth and on the activities of alkaline phosphatase (AP) and dipeptidyl aminopeptidase IV (DPP IV) by three human colonic adenocarcinoma cell lines. In addition to butyrate, propionate and valerate inhibited cell proliferation of the three cell lines. The other SCFAs did not influence cell proliferation. AP and DPP IV activities were strongly stimulated by butyrate on two of the three cell lines. On HT-29, AP was strongly stimulated, however DPPIV expression remained undetectable. Propionate and valerate exhibited a weaker stimulation, the other SCFAs being ineffective. The effect of SCFAs on cell proliferation and differentiation clearly depends on the number of carbons and on the configuration of the basic structure of the molecule.     

伏核在躯体传入冲动抑制防御性心血管反应中的作用及机制

损毁伏核可明显削弱电刺激腓深神经（ＤＰＮ）对兴奋下丘脑背内侧核诱发的升压反应和心肌缺血的抑制作用（Ｐ＜０．０５,Ｐ＜０．０１）。电刺激伏核可引起明显的降压效应。中脑中央灰质腹侧部（ｖＰＡＧ）微量注射纳洛酮可明显衰减伏核的减压效应;损毁ｖＰＡＧ甚至可翻转伏核的减压效应,引起轻度升压（Ｐ＜０．０１）。损毁弓状核后伏核的减压效应基本消失,弓状核内微量注射纳洛酮明显衰减伏的的减压效应。故ＤＰＮ传入冲动可能     

Electromagnetic stimulation blocks isometric twitch contraction in the frog sciatic nerve-gastrocnemius muscle preparation

The effect of electromagnetic stimulation (EMS) on nerve conduction and muscle twitch contraction was studied in isolated sciatic nerve-gastrocnemius muscle of the frog. Electrical stimulation (ES) of the sciatic nerve produced twitch contractions in the gastrocnemius muscle and these responses were reduced and eventually blocked by EMS, applied to the nerve simultaneously with ES, from a d.c. source at a certain frequency and duration of the induced current. The EMS-induced inhibition of the twitch contractions was reversible, and this depended on the induced current and its duration. The possibility that other factors may have contributed to the inhibition of twitch contractions, such as a rise in temperature, was also investigated. It was concluded that EMS inhibited indirectly-elicited twitch contractions produced by ES in the frog nerve-muscle preparation.