胃动素对大鼠下丘脑胃牵张敏感神经元和胃运动的影响(英文)

目的:研究胃动素对下丘脑弓状核胃牵张敏感神经元放电活动和胃运动的影响。方法:采用4管玻璃微电极细胞外记录胃动素对大鼠弓状核胃牵张敏感神经元活动,采用胃内置传感器观察胃动素对对清醒大鼠胃运动的影响。结果:65.5%的弓状核神经元为胃扩张敏感性神经元,其中55.6%为胃扩张兴奋性神经元,44.4%为抑制性神经元。胃扩张刺激后兴奋性神经元的放电频率显著增加(P<0.01),而抑制性神经元的放电频率显著降低(P<0.01)。弓状核内微量注射胃动素,70%的兴奋性神经元在胃扩张刺激后表现为兴奋作用,17.5%的神经元表现为抑制作用,并且放电频率显著增加(P<0.05)。同样,在抑制性神经元中,65.6%在注射胃动素后引起电活动增强,放电频率显著降低(P<0.05)。而胃动素受体拮抗剂GM-109可以完全阻断这种由胃动素诱导的兴奋作用,提示,胃动素在弓状核通过其特异性受体调控神经元活动。在胃运动实验中,弓状核微量注射胃动素后,胃运动的收缩频率和幅度都显著增加(P<0.05);同时,这种兴奋作用也可被GM-109阻断。结论:研究证实了弓状核胃动素神经元接收来自胃感受器的外周躯体感觉传入神经的冲动,并通过某些下级核团通路发挥...     

大鼠性周期内缰核神经元电活动的变化

目的：探讨缰核与生殖神经内分泌功能的关系。方法：采用电生理学方法记录细胞外放电。结果：①本实验观察到动情前期及动情间期大鼠缰核（ｈａｂｅｎｕｌａｒ ｎｕｃｌｅｕｓ,Ｈｂ） 的神经元对阴道、宫颈刺激（ｖａｇｉｎｏｃｅｒｖｉｃａｌｓｔｉｍｕｌａｔｉｏｎ,ＶＣ刺激） 发生两种反应。一类神经元对ＶＣ 刺激发生放电频率增快或持续时间延长的反应,即ＶＣＥ 神经元,另一类神经元则对ＶＣ刺激发生放电频率降低或暂时终止的反应,即ＶＣＩ神经元。动情前期大鼠的ＶＣＥ及ＶＣＩ神经元多呈周期性放电;②本实验还发现,大鼠Ｈｂ 中对ＶＣ刺激发生反应的性相关神经元中多数为非特异性反应型神经元,即对ＶＣ刺激和夹尾等其它刺激发生兴奋或抑制反应,少数为特异反应型神经元,即只对ＶＣ 刺激发生反应。结论：①提示这两种神经元可能与神经分泌活动有关; ②特异反应型神经元的存在表明,Ｈｂ 可以接受ＶＣ刺激的传入信息,并对其发生反应。ＶＣ刺激可能通过影响Ｈｂ 神经元的活动,从而影响生殖神经内分泌功能     

下丘脑穹窿周围区不同部位兴奋对心肌Po2及ECG—ST的影响

电刺激下丘脑穹窿周围区（ＰＦＡ）的下丘脑背内侧核（ＤＭＨ）,下丘脑腹内侧核（ＶＭＨ）与下丘脑外侧区（ＬＨＡ）均可引起心肌Ｐｏ２下降与血压升高,而以ＤＭＨ所致的心肌Ｐｏ２下降最明显。心得安可取消电刺激ＬＨＡ所致的心肌Ｐｏ２下降,部分取消电刺激ＶＭＨ引起的心肌Ｐｏ２下降,而不改变电刺激ＤＭＨ所致的心肌Ｐｏ２下降。ＤＭＨ、ＶＭＨ微量注射谷氨酸钠均可诱发升压反应和ＥＣＧ－ＳＴ压低,而ＬＨＡ微量注射谷氨酸却     

杏仁核内注射CCK—8抑制胃运动的机制

应用脑核团内微量注射和核团电刺激方法,观察杏仁基底内侧（ＢＭＡ）对胃运动的影响,分析ＢＭＡ与下丘脑腹内侧核（ＶＭＨ）的机能联系。结果如下：（１）双侧ＢＭＡ内注射八肽胆囊收缩素（ＣＣＫ－８）（５０ｎｇ／ｌμｌ）,出现胃内压（ＩＧＰ）和胃运动频率（ＧＭＦ）显著下降（Ｐ〈０．０１）。（２）ＢＭＡ内注射ＣＣＫ－Ａ受体阻断剂［Ｌ３６４,７１８］（１００ｎｇ／ｌμｌ）或ＣＣＫ－Ｂ受体阻断剂［Ｌ３６５,２６０］     

侧脑室注射血管紧张素Ⅱ对大鼠血压和缰核内神经元电活动的影响

实验观察了侧脑室注射（ｉｃｖ）及缰核（ｈａｂｅｎｕｌａ ｎｕｃｌｅｕｓ）内微电泳血管紧张素Ⅱ（ＡⅡ）与「Ｓａｒ＾１,Ｔｈｒ＾３」－ＡⅡ（ＳＴ－ＡⅡ,ＡⅡ拮抗剂）对正常和诮激性高血压（ｓｔｒｅｓｓ－ｉｎｄｕｃｅｄ ｈｙｐｅｒｔｅｎｓｉｏｎ ＳＩＨ）大鼠血压及内外侧缰核（ＭＨｂ、ＬＨｂ）内心血管神经元入电活动的影响。结果如下：ｉｃｖ ＡⅡ或ＳＴ－ＡⅡ,正常鼠和ＳＩＨ大鼠血压均升高或降低,ＳＩＨ鼠较正常     

下丘脑穹窿周围区不同部位兴奋对心肌Po_2及ECG－ST的影响

电刺激下丘脑穹窿周围区（ＰＦＡ）的下丘脑背内侧核（ＤＭＨ）,下丘脑腹内侧核（ＶＭＨ）与下丘脑外侧区（ＬＨＡ）均可引起心肌Ｐ０＿２下降与血压升高,而以ＤＭＨ所致的心肌Ｐ０,下降最明显（Ｐ＜０．０１）。心得安可取消电刺激ＬＨＡ所致的心肌ＰＯ＿２下降,部分取消电刺激ＶＭＨ引起的心肌ＰＯ＿２下降,而不改变电刺激ＤＭＨ所致的心肌ＰＯ＿２下降（Ｐ＞０．０５）。ＤＭＨ、ＶＭＨ微量注射谷氨酸钠（０．１ｍｏｌ／Ｌ０．５μｌ）均可诱发升压反应和ＥＣＧ－ＳＴ压低,而ＬＨＡ微量注射谷氨酸却导致降压反应,对ＥＣＧ－ＳＴ无明显影响。上述结果提示ＤＭＨ为ＰＦＡ各区诱发心肌缺血缺氧的主要核团。兴奋ＤＭＨ、ＶＭＨ所致的心血管效应主要由胞体兴奋诱发,而电刺激ＬＨＡ所致的升压反应主要为兴奋过路纤维引起,该区胞体兴奋主要导致降压反应。     

迷走背核微量注射P物质抑制大鼠胃肌电活动和胃运动

本工作观察到大鼠迷走背核微量注射Ｐ物质（Ｓｕｂｓｔａｎｃｅ Ｐ,ＳＰ）抑制胃肌电快波和胃运动。该效应可分别迷走背核注射ＳＰ抗血清,ＳＰ受体拮抗剂「Ａｒｇ＾６,Ｄ－Ｔｒｐ＾７,９,Ｎ－Ｍｅ－Ｐｈｅ＾８」－ＳＰ６－１１或切断迷走神经所消除。用利血平耗竭交感神经递质则不影响该效应。     

下丘脑室旁核胃动素对胃运动影响的探讨

目的 :研究下丘脑室旁核 (paraventricularnucleus,PVN)胃动素对胃运动调节的参与作用及机制。 方法 :应用免疫组织化学的方法检测室旁核内胃动素神经元的表达情况及室旁核与延髓迷走复合体 (dorsalvagalcomplex ,DVC)间的神经联系 ,应用室旁核内微量注入胃动素的方法观察清醒大鼠胃运动的变化。结果 :①下丘脑室旁核有胃动素免疫阳性细胞 ,在饥饿组和十二指肠灌酸组 ,阳性细胞数有明显增加 (P <0 .0 1)。②迷走背核注入辣根过氧化物酶 (horseradishperoxidase ,HRP) ,在室旁核发现HRP标记细胞 ,证实室旁核与DVC间的纤维联系。③清醒大鼠室旁核内微量注射胃动素可使胃运动的幅度和频率明显增加 (P <0 .0 5 ) ,切断双侧膈下迷走神经后 ,胃动素对胃运动的作用消失。结论 :下丘脑室旁核内胃动素可增强胃运动 ,其作用可能是通过下丘脑 延髓迷走复合体 迷走神经实现的     

强直电刺激嗅内皮质—海马环路诱发CAI神经元的癫痫同步性膜电位振？…

目的和方法：４００－５００μｍ大鼠水平脑切片吸封闭的ＥＣ－海马环路。强直电刺激（６０Ｈｚ,２ｓ）海马Ｓｃｈａｅｆｆｅｒ侧支诱发癫痫放电,全细胞记录ＣＡ１胞体层单个神经元电活动,同步记录相应树突外场电位,探讨单个神经元膜电位振荡特性和细胞外癫痫电活动之间的关系。结果：（１）强直电刺激诱发ＣＡ１神经元膜电位后放性振呈宽频特征（３－１００ＨＺ）。以θ节律多见,跟随在刺激引起的膜电位去极化或超极化偏移之后     

大鼠下丘脑外侧区内微量注射胃动素对胃窦运动和迷走背核复合体神经元电活动的影响

采用清醒大鼠胃运动记录和玻璃微电极记录神经元活动的实验方法 ,研究下丘脑外侧区 (lateralhy pothalamicarea,LHA)微量注射胃动素 (motilin) ,对清醒大鼠胃窦运动和对麻醉大鼠迷走背核复合体 (dorsalvagalcomplex ,DVC)中胃扩张敏感神经元电活动的调节作用。LHA内微量注射胃动素 (0 37nmol/ 0 5 μl)可使胃窦运动增强 76 2 9± 4 0 9% (P <0 0 1)。DVC中 6 0个胃扩张 (gastricdistention ,GD)敏感神经元中 ,39(6 5 % )个GD刺激引起电活动增强 ,2 1(35 % )个电活动减弱 ,分别称之为GD兴奋型神经元和GD抑制型神经元。双侧LHA微量注射胃动素 0 37nmol/ 0 5 μl,14个GD抑制型神经元中有 12个单位放电频率增加 4 4 35± 7 89% (P <0 0 1) ;2 4个GD兴奋型神经元中有 15个单位放电频率减少 7 17± 7 89% (P <0 0 5 )。结果提示 ,中枢胃动素可能通过LHA-DVC-迷走神经实现对胃窦运动的调控     

Orexin-A对大鼠胃功能的影响

目的:探讨Orexin-A对大鼠胃功能的影响。方法:通过大鼠迷走神经复合体微量注射Orexin-A后,观察大鼠胃运动、胃液和胃酸分泌的变化。结果:DVC微量注射Orexin-A后,大鼠胃收缩幅度以及收缩频率明显升高,且呈明显剂量依赖关系(P0.05),SB334867可显著阻断Orexin-A对促胃运动效应(P0.05)。DVC微量注射orexin-A后,大鼠胃液及胃酸分泌且呈剂量依赖性增加(P0.05)。结论:迷走神经复合体微量注射Orexin-A能影响胃的运动以及胃内体液的分泌。     

Motilin activates neurons in the rat amygdala and increases gastric motility

Motilin and motilin receptors have been found in most regions of the brain, including the amygdala, one of the most important parts of the limbic system. Our previous study found that administration of motilin in the hippocampus stimulates gastric motility. We now explore the effect of motilin in the amygdala on gastric motility. In conscious rats, gastric motility was recorded after microinjection of motilin, motilin receptor antagonist (GM-109) or a mixture of the two into the basomedial amygdala nucleus (BMA). In anesthetized rats the changes of spontaneous discharges of gastric distention sensitive neurons (GDSN) in the BMA were recorded after intracerebroventricular (i.c.v.) microinjection of motilin or GM-109. In conscious rats the amplitude of gastric contractions increased dose-dependently after microinjection of motilin in the BMA, and decreased after microinjection of GM-109. The excitatory or inhibitory effects induced by motilin or GM-109 alone, were weakened by microinjection of a mixture solution of both. The spontaneous discharge frequency of gastric distention excitatory neuron (GDEN) was mainly inhibited by i.c.v. microinjection of motilin but excited by GM-109. In contrast, the spontaneous discharge frequency of gastric distention inhibitory neuron (GDIN) was mainly excited by motilin, but inhibited by GM-109. Our findings suggest that motilin may regulate gastric motility by modulating neural pathways in the BMA.     

Acute lesions of the ventromedial hypothalamus reduce sympathetic activation and thermogenic changes induced by PGE1

The aim of this experiment was to evaluate the effects of an intracerebroventricular (icv) injection of prostaglandin E1 (PGE₁) on the sympathetic activation and the thermogenic changes in rats with acute lesions of the ventromedial hypothalamus (VMH). Four groups of six Sprague-Dawley male rats were anesthetized with ethyl-urethane. The firing rate of the sympathetic nerves innervating the interscapular brown adipose tissue (IBAT) and the colonic and IBAT temperatures were monitored both before and after one of the following treatments: 1) VMH lesion plus icv injection of PGE₁ (500 ng); 2) VMH lesion plus icv injection of saline; 3) sham lesion plus icv injection of PGE₁; and 4) sham lesion plus icv injection of saline. PGE₁ induced an increase in the firing rate of IBAT nerves and the colonic and IBAT temperatures. These effects were reduced by VMH lesion. The findings indicate that acute lesions of the VMH reduce the effects of PGE₁ and seem to suggest a possible role played by the VMH in the control of the sympathetic activation and the thermogenic changes during PGE₁ hyperthermia.     

Effects of ghrelin on glucose-sensing and gastric distension sensitive neurons in rat dorsal vagal complex

Ghrelin has been identified as the endogenous ligand of the growth hormone secretagogue receptor (GHS-R). Recent studies have shown that site-specific injection of ghrelin directly into the dorsal vagal complex (DVC) of rats is equally as sensitive in its orexigenic response to ghrelin as the arcuate nucleus of the hypothalamus (ARC). It is as yet unclear how circulating ghrelin would gain access to and influence the activity of the neurons in the DVC in which GHS receptors are expressed. In the present study, neuronal activity was recorded extracellularly in the DVC of anesthetized rats in order to examine the effects of ghrelin on the glucosensing neurons and the gastric distension (GD) sensitive neurons. The 82 neurons were tested with glucose, of which 26 were depressed by glucose and identified as glucose-inhibited (glucose-INH) neurons; 11 were activated and identified as glucose-excited (glucose-EXC) neurons. Of 26 glucose-inhibited neurons examined for response to ghrelin, 23 were depressed, 1 was activated, and 2 failed to respond to ghrelin. Nine of 11 glucose-excited neurons were suppressed by ghrelin application, and the responses are abolished by the pretreatment with the GHS-R antagonist, [D-Lys-3]-GHRP-6. In addition, of 47 DVC neurons examined for responses to gastric distension (GD), 25 were excited (GD-EXC), 18 were inhibited (GD-INH). 18 out of the 25 GD-EXC neurons were excited, whereas 15 out of 18 GD-INH neurons were suppressed by ghrelin. In conclusion, the activity of the glucosensing neurons in the DVC can be modulated by ghrelin, the primary effect of ghrelin on the glucose-INH and glucose-EXC neurons was inhibitory. Two distinct population of GD-sensitive neurons exist in the rat DVC: GD-EXC neurons are activated by ghrelin; the GD-INH neurons are suppressed by ghrelin. There is a diversity of effects of ghrelin on neuronal activity within the DVC, it is as yet unclear how this diversity in ghrelin's effects on cellular excitability contributes to ghrelin biological actions to influence food intake and gastric motility.     

Interdigestive migrating contractions are coregulated by ghrelin and motilin in conscious dogs

During fasting, gastrointestinal (GI) motility is characterized by cyclical motor contractions. These contractions have been referred to as interdigestive migrating contractions (IMCs). In dogs and humans, IMCs are known to be regulated by motilin. However, in rats and mice, IMCs are regulated by ghrelin. It is not clear how these peptides influence each other in vivo. The aim of the present study was to investigate the relationship between ghrelin and motilin in conscious dogs. Twenty healthy beagles were used in this study. Force transducers were implanted in the stomach, duodenum, and jejunum to monitor GI motility. Subsequent GI motility was recorded and quantified by calculating the motility index. In examination 1, blood samples were collected in the interdigestive state, and levels of plasma ghrelin and motilin were measured. Plasma motilin peaks were observed during every gastric phase III, and plasma ghrelin peaks occurred in nearly every early phase I. Plasma motilin and ghrelin levels increased and decreased cyclically with the interdigestive states. In examination 2, saline or canine ghrelin was administered intravenously during phase II and phase III. After injection of ghrelin, plasma motilin levels were measured. Ghrelin injection during phases II and III inhibited phase III contractions and decreased plasma motilin levels. In examination 3, ghrelin was infused in the presence of the growth hormone secretagogue receptors antagonist [D-Lys3]-GHRP-6. Continuous ghrelin infusion suppressed motilin release, an effect abrogated by the infusion of [D-Lys3]-GHRP-6. Examination 4 was performed to evaluate the plasma ghrelin response to motilin administration. Motilin infusion immediately decreased ghrelin levels. In this study, we demonstrated that motilin and ghrelin cooperatively control the function of gastric IMCs in conscious dogs. Our findings suggest that ghrelin regulates the function and release of motilin and that motilin may also regulate ghrelin.     

Dual effect of bombesin and gastrin releasing peptide on gastric emptying in conscious cats

The effect of bombesin (BBS) and gastrin releasing peptide (GRP) on gastric emptying was studied in conscious cats. This effect was measured simultaneously with antral motility. Acid and pepsin secretions as well as blood hormonal peptide release were additionally measured. A dual effect was observed. First, BBS and GRP slowed gastric emptying of liquids, while antral motility was decreased, then after 60 minutes of continuous intravenous infusion, antral motility returned to basal values and gastric emptying effect reversed. The mechanism of this peculiar action is independent of gastrin, pancreatic polypeptide, somatostatin and motilin release and most probably connected with a cholinergic stimulation induced by the peptides, the late predominance of which counterbalances the inhibitory effect of bombesin-like peptides on antral motility.     

Interleukin-1 inhibits stress-induced gastric erosion in rats

The effect of interleukin (IL)-1 on the occurrence of stress-induced gastric erosions was examined in rats. The intracerebroventricular (icv) administration of IL-1 beta significantly inhibited the occurrence of water-immersion restraint stress-induced gastric erosion at doses of 200 ng, 500 ng and 1 microgram, whereas the intravenous (iv) administration of IL-1 beta altered the occurrence of gastric erosion only at a dose of 1 microgram. The inhibitory effect of IL-1 alpha icv administered on the occurrence of gastric erosion was found only at a dose of 1 microgram. The inhibitory effect of IL-1 beta icv administered on the occurrence of stress-induced gastric erosion was not influenced by icv administration of alpha-helical CRF(9-41), a corticotropin-releasing factor (CRF) receptor antagonist. Indomethacin completely blocked the inhibitory action of IL-1 beta icv administered on stress-induced gastric erosion. It is concluded from these results that IL-1 acts mainly in the central nervous system to inhibit the occurrence of stress-induced gastric erosion and that the IL-1 beta-induced inhibition of gastric erosion is mediated by prostaglandin in a manner that is independent of brain CRF.     

LPS-induced suppression of gastric motility relieved by TNFR:Fc construct in dorsal vagal complex

Our previous studies suggested that the cytokine tumor necrosis factor-alpha (TNF-alpha) may act within the neural circuitry of the medullary dorsal vagal complex (DVC) to affect changes in gastric function, such as gastric stasis, loss of appetite, nausea, and vomiting. The definitive demonstration that endogenously generated TNF-alpha is capable of affecting gastric function via the DVC circuitry has been impeded by the lack of an antagonist for TNF-alpha. The present studies used localized central nervous system applications of the TNF-adsorbant construct (TNFR:Fc; TNF-receptor linked to the Fc portion of the human immunoglobulin IgG1) to attempt to neutralize the suppressive effects of endogenously produced TNF-alpha. Gastric motility of thiobutabarbital-anesthetized rats was monitored after systemic administration of lipopolysaccharide (LPS) to induce TNF-alpha production. Continuous perfusion of the floor of the fourth ventricle with TNFR:Fc reversed the potent gastroinhibition induced by LPS, i.e., central thyrotropin-releasing hormone-induced increases in motility were not inhibited. This disinhibition of gastric stasis was not seen after intravenous administration of similar doses of TNFR:Fc nor ventricular application of the Fc fragment of human immunoglobulin. These results validate our previous studies that suggest that circulating TNF-alpha may act directly within the DVC to affect gastric function in a variety of pathophysiological states.