瘦素对幼龄厌食大鼠VMN神经元膜电位改变的影响

目的：观察瘦素对幼龄厌食大鼠下丘脑腹内侧核（VMN）神经元膜电位的影响。方法：利用红外可视膜片钳技术记录对照组、模型组两组动物VMN神经元的膜电位，分析瘦素对VMN神经元膜电位的影响。结果：瘦素使两组动物大部分神经元去极化，组间比较无显著性差异。少数VMN神经元在瘦素作用下超极化，组间比较亦无显著性差异。然而，模型组VMN神经元的膜电位被瘦素去极化而导致自发放电增加的细胞比例增多，被瘦素超极化而自发放电减少的细胞比例减少，对瘦素无反应的细胞比例也减少。结论：造模因素可能通过提高VMN对瘦素的整体敏感性，使VMN发出过度的饱信号，从而产生厌食，这应当是小儿厌食发生发展的中枢机制之一。     

下丘脑腹内侧区注射内皮素对猫心血管系统活动的影响

为探讨内皮素对心血管中枢活动的影响，我们观察了猫下丘脑腹内侧区注射内皮素对心血管功能活动的影响．结果发现，实验条件下内皮素对正常血压，左心室压，心率等指标并无明显影响．它可能反映内皮素受体分布及其功能的差异．     

宝宝乐口服液对瘦素调节VMN神经元mIPSC的影响

目的 观察中药宝宝乐口服液对瘦素调节下丘脑腹内侧区（VMH）神经元mIPSC的影响。方法 利用红外可视脑片膜片钳技术记录对照组、模型组和治疗组3组实验大鼠VMN神经元的mIP-SC，取给药前1min和给药最后1min的数据，分析瘦素及宝宝乐口服液对mIPSC频率的影响。结果 瘦素使3组大鼠大部分VMN神经元的mIPSC频率减少，小部分VMN神经元的mIPSC频率增加。mIP-SC频率抑制或增加的程度在3组间无显著性差异（P〉0．05），但模型组mIPSC频率抑制的神经元比例显著多于对照组（P〈0．05），而mIPSC增加的神经元显著少于对照组（P〈0．05），且模型组mIPSC对瘦素无反应的神经元比例也减少；治疗组中mIPSC频率抑制或增加的程度恢复正常。结论 厌食模型动物VMN对瘦素的整体敏感性增加，使VMN发出过度的饱信号，从而产生厌食；宝宝乐口服液可以纠正和改善这一病理过程，这应当是小儿厌食发生发展及运脾复方作用的中枢机制之一。     

奥拉西坦对大鼠下丘脑神经元钠钾通道电流的作用

目的 研究在奥拉西坦作用下大鼠下丘脑神经元钠钾通道电流的变化。方法 应用膜片钳技术的全细胞方法记录奥拉西坦作用下大鼠下丘脑神经元钠钾通道电流。结果 在奥拉西坦作用下，下丘脑神经元平均Na^＋电流由（4．130±0．210）hA上升为（5．950±0．411）nA，平均K＋电流由（5．601±0．221）nA增加为（7．550±0．403）nA，而且作用前后比较有统计学差异。结论 在奥拉西坦的作用下，下丘脑神经元Na^＋，K^＋电流均增大，从而增加了神经元细胞动作电位的幅值及传导速度，使动作电位的传导更加容易。     

针刺对未成年雄性家兔下丘脑弓状核核团放电的影响

下丘脑弓状核属于下丘脑神经分泌小细胞系统,是下丘脑的重要核团之一,与脉冲式释放促性腺激素释放激素（GnRH）有非常密切的关系。而GnRH对于性发育的启动和促进、性成熟的维持具有重要的作用。本研究旨在通过比较针刺前后未成年雄性家兔下丘脑弓状核核团放电情况,初步探讨针刺对未成年雄性家兔下丘脑弓状核核团放电的影响。     

吗啡对吗啡依赖大鼠腹侧苍白球神经元放电的影响

目的 :研究吗啡对吗啡依赖大鼠腹侧苍白球的电生理影响 ,探讨其在成瘾机制中的作用。方法 :通过单细胞细胞外记录吗啡依赖大鼠腹侧苍白球的电信号 ,观察吗啡对放电的影响。结果 :吗啡依赖大鼠腹侧苍白球神经元放电频率给药前为 3 76Hz±s 1 18Hz,注射吗啡后为 13 2 2Hz±s 2 37Hz;并且纳洛酮可以逆转这种兴奋效应。结论 :吗啡显著兴奋吗啡依赖大鼠腹侧苍白球神经元 ,腹侧苍白球在药物强化过程中起着重要作用。     

神经肽urocortin Ⅱ对吗啡成瘾大鼠中脑腹侧被盖区神经元自发放电的影响

<正>吗啡等阿片类药物反复使用可造成耐受、依赖和成瘾,中断给药出现戒断综合征、强迫觅药行为及戒断后焦虑等精神神经系统症状,对患者的身心有严重影响。目前已知,中脑边缘-多巴胺系统与药物成瘾和强化作用形成密切相关,此系统起自中脑腹侧被盖区(ventral tegmental area,VTA),投射到杏仁中央核(nucleus centralis amygdalae,NAC)、内侧前额叶皮层(mPFC)等前脑区域,并涉及多种神经递质的投射。其中VTA是中脑的重要神经核团,在此系统中发挥非常关键的作用,因此受到人们的关注。神经肽urocortin(UCN)是由40个氨基酸组成的高活性神经肽,属促肾上腺皮质激素释放因子(CRH)家族,与CRF具有相似的生物学     

染料木黄酮对大鼠下丘脑脑片室旁核神经元放电的影响(英文)

目的研究染料木黄酮(GST)在心血管中枢神经系统的作用。方法应用细胞外记录单位放电技术,在下丘脑脑片上观察GST对静息状态下的室旁核神经元放电的影响。结果①26个脑片分别灌流GST 10,50,100μmol·L~(-1)2 min,有25个脑片放电频率明显降低,且呈浓度依赖性;②用0.2 mmol·L~(-1) L-谷氨酸灌流脑片,7/7个脑片放电频率明显增加,表现为癫痫样放电,在此基础上加灌GST 50μmol·L~(-1)2 min,其癫痫样放电被抑制;③用G蛋白激活的内向整流型钾通道阻断剂四乙胺1 mmol·L~(-1)灌流脑片,约10 min后加入GST 50μmol·L~(-1),8/8个脑片的放电抑制效应被完全阻断;④用一氧化氮合酶抑制剂左旋硝基精氨酸甲酯50μmol·L~(-1)灌流脑片,7/7个脑片的放电频率增加,在此基础上加灌GST 50μmol·L~(-1)2 min,放电被抑制。结论GST可抑制下丘脑室旁核神经元自发放电,并抑制L-谷氨酸诱发的神经元癫痫样放电。这种抑制作用可能与激活G蛋白激活的内向整流型钾通道,促进K~+外流,从而引起细胞膜超极化有关;而与NO释放无关。GST可能通过降低心血管中枢的活动性而产生一定的心血管系统保护作用。     

膳食变化对大鼠下丘脑 AgRP 表达的影响

目的：分析膳食变化对大鼠下丘脑刺鼠相关蛋白（ AgRP）表达的影响,探讨AgRP在肥胖发生中的作用,为肥胖的研究提供一个新的思路。方法将80只体重为100～120 g的雄性Wistar大鼠随机分成高能饲料组（ n＝40）、饥饿组（ n ＝20）、对照组（ n ＝20）。高能组给予自制的高能饲料,对照组和饥饿组给予基础大鼠饲料。12周后,高能组体重超过对照组平均体重30％的大鼠设为膳食诱导肥胖（ DIO）组,饥饿组给予72 h禁食,自由饮水。取大鼠下丘脑采用免疫组化实验和western blot检测AgRP表达。结果免疫组化显示DIO组大鼠和饥饿组大鼠下丘脑AgRP表达显著高于对照组（ P ＜0滗．05）;而DIO组大鼠和饥饿组下丘脑AgRP表达差异无统计学意义（ P ＞0．05）。Western Blot实验显示DIO组和饥饿组大鼠下丘脑AgRP表达明显高于对照组大鼠（ P ＜0．01）。而DIO组大鼠和饥饿组大鼠下丘脑AgRP表达差异无统计学意义（ P ＞0．01）。结论长期高能饮食导致肥胖,其下丘脑内AgRP表达的增高可能是导致机体摄食量和体重增加并引起肥胖的主要因素之一。饥饿状态下,下丘脑内AgRP表达增高,可能是由于在饥饿状态下机体内瘦素、胰岛素、糖的减少共同所致。     

利拉鲁肽对食源性肥胖大鼠下丘脑p38丝裂原活化蛋白激酶信号通路的影响

目的 研究利拉鲁肽对食源性肥胖大鼠的治疗效果，并探讨其对p38丝裂原活化蛋白激酶(p38 MAPK)信号通路的影响。方法 以饲喂高脂饲料的方法建立食源性肥胖大鼠模型。将31只食源性肥胖大鼠随机分为模型组(n=11)、利拉鲁肽组(n=10)、联合组(n=10),另取10只健康大鼠做为对照组。利拉鲁肽组腹腔注射0.6 mg·kg^-1利拉鲁肽注射液，联合组腹腔注射0.6 mg·kg^-1利拉鲁肽注射液+2 mg·kg^-1茴香霉素，对照组、模型组腹腔注射等体积生理盐水。每天1次，持续2周。以全自动生化分析仪检测大鼠血脂指标；以脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)染色检测下丘脑弓状核神经元凋亡率；以蛋白质印迹法检测下丘脑组织p38 MAPK、p-p38 MAPK、细胞外信号调节激酶(ERK1/2)、p-ERK1/2蛋白表达水平。结果 利拉鲁肽组、联合组、对照组、模型组的体脂比分别为(3.34±0.35)%、(3.61±0.38)%、(2.38±0.25)%和(3.94±0.41)%;三酰甘油(TG)分别为(1....     

Effects of ovariectomy and estradiol injections on food intake and body weight in rats with ventromedial hypothalamic lesions

Female rats with lesions of the ventromedial hypothalamus (VMH) were ovariectomized during the static obese stage efter body weight levels had stabilized. Following ovariectomy, rats with VMH lesions showed smaller increases in food intake and less body weight gain than non-lesioned controls ovariectomized at the same time. Subsequently, the effects of peripheral injections of estradiol benzoate (EB) on feeding and body weight were examined. Ovariectomized rats with VMH lesions were also less responsive to exogenous EB treatment; they lost significantly less weight in response to estrogen than controls. EB caused a somewhat smaller reduction in food intake by the VMH group but this difference was not significant. Considered together the available data on changes in responsiveness to endogenous and exogenous estrogen following VMH lesions suggests a role for VMH estrogen receptors in the regulation of body weight, but these estrogen receptors may not modulate weight by directly altering food intake as previously suggested.     

Effects of angiotensin II on central neurons

Effects of angiotensin II administered intravenously and by means of electrophoresis through multibarrel micropipette electrodes on the frequency of extracellularly recorded action potentials of brain cells were determined. A total of 293 neurons in seven different parts of the brains of male and female hooded rats anesthetized with urethan or a mixture of urethan and chloralose were tested. Results indicate that angiotensin affects many different cells within the lateral hypothalmus, zona incerta, ventromedial and dorsomedial hypothalamic nuclei, dentate gyrus and thalamus. The cells of the LH and zona incerta are the most sensitive to angiotensin and two types of lateral hypothalamic neurons were found which were affected differently by angiotensin and stimulation of the basolateral amygdaloid nucleus. Some of the Na sensitive neurons, all of which were sensitive to angiotensin, displayed a very pronounced potentiation of discharge frequency when angiotensin and Na were administered simultaneously. Angiotensin II might therefore influence drinking because of a relatively low threshold effect on hypothalamic neurons.     

Involvement of hypothalamic periventricular GABAergic nerves in the central pressor response to clonidine in freely-moving conscious rats

Microinjection of the α(2)-adrenoceptor agonist clonidine into the hypothalamic periventricular nuclei (PVN) induces the pressor response associated with bradycardia in freely-moving conscious rats. This study investigated the involvement of γ-aminobutyric acid nerves (GABAergic nerves) and glutamatergic nerves in the cardiovascular response to microinjection of clonidine in the PVN. Male Wistar rats were chronically implanted with a microinjection cannula into the PVN and an arterial catheter into the abdominal aorta through the femoral artery. Blood pressure and heart rate were measured under a conscious unrestrained state. PVN injection of clonidine induced a dose-dependent pressor response concomitant with bradycardia. PVN pretreatment with GABA, muscimol (GABA(A)-receptor agonist), or bicuculline (GABA(A)-receptor antagonist) significantly inhibited the pressor response to PVN-injected clonidine without affecting bradycardia. PVN pretreatment with baclofen (GABA(B)-receptor agonist), 2-hydroxysaclofen (GABA(B)-receptor antagonist), or kynurenic acid (non-selective NMDA-type glutamate-receptor and ionotropic glutamate-receptor antagonist) did not affect the pressor response to PVN-injected clonidine. These results suggest that clonidine induces a pressor response by stimulating the presynaptic α(2)-adrenoceptor of GABAergic nerves in the PVN, thereby inhibiting GABAergic nerve activity.     

大鼠海马神经元癫痫样放电模型的构建

目的探讨“无镁细胞外液”诱导体外培养大鼠海马神经元产生癫痫样放电的可行性,以期建立难治性癫痫离体细胞模型。方法选取24h内新生Wistar大鼠,分离海马神经元后进行原代培养,体外培养至第12天时,用“无镁细胞外液”处理3h,应用全细胞膜片钳技术记录海马神经元的放电情况。结果在培养第12天时,神经元突起间彼此接触形成神经网络。在“无镁细胞外液”处理3h后神经元产生稳定的放电,恢复正常细胞培养液培养24h,神经元仍可检测到自发的“癫痫样放电”。结论体外培养第12天海马神经元,在“无钱细胞外液”处理后可形成稳定的自发性癫痫样放电,为今后在细胞分子水平研究癫痫发病机制提供了一种理想模型。     

Anesthetics produce differential actions on the discharge activity of a single neuron

The effects of 26 anesthetic agents were studied on the rhythmical discharge activity of a single isolated neuron (crayfish stretch receptor). Many of these agents produced concentration-dependent biphasic responses (excitation and depression), and some also induced altered discharge patterns (burst activity). The dominant effect of a few of the anesthetics was excitation (e.g. alphaxolone); depression (e.g. decanol); or burst activity (e.g. benzocaine). A correlation was found to exist between equieffective concentrations in the perfusate and membrane/buffer partition coefficients; however, this general phenomenon does not provide an explanation for the biphasic or differential responses. These results demonstrate that selective interactions occur at the level of the single neuron, and suggest the existence of recognition sites in neuronal membranes which can discriminate structural differences of anesthetics.     

六君子汤加味联合甲地孕酮治疗结肠癌手术化疗后厌食症的疗效观察

目的观察六君子汤加味联合甲地孕酮治疗结肠癌手术病人化疗后厌食症的疗效。方法选取 2021年 1月至 2022年 4月唐山市中医医院诊治的结肠癌手术化疗后厌食症病人 60例作为研究对象。根据信封法随机将病人分为对照组( 30例,甲地孕酮治疗)和观察组( 30例,六君子汤加味联合甲地孕酮治疗)。比较两组中医症状积分、体质量和厌食评分、营养指标(白蛋白、前白蛋白)、胃肠激素(胃泌素、胃动素)水平、生活质量评分( QOL评分)以及临床疗效。结果观察组总有效率为93.33%,高于对照组的 73.33%(P<0.05);治疗后观察组恶心呕吐［(1.02±0.21)分比( 1.35±0.28)分］、脘腹胀满［(1.12±0.32)分比(1.47±0.35)分］、嗳气反酸［( 0.89±0.22)分比( 1.43±0.27)分］、脘腹疼痛［( 0.95±0.23)分比( 1.52±0.28)分］等中医证候积分和 NRS评分均低于对照组( P<0.05);而体质量、血清白蛋白水平、血清前白蛋白水平、胃泌素水平、胃动素水平、 QOL评分均高于对照组( P<0.05)。结论六君子汤加味联合甲地孕酮治疗结肠癌手术病人化疗后厌食症可减轻病人临床症状,增加食欲,增强胃肠功能、改善营养状况,提高生活质量,疗效显著。     

Effect of haloperidol on glutamete decarboxylase activity in discrete brain areas of the rat

Using freeze-dried samples of rat brain, the effect of haloperidol on glutamate decarboxylase (GAD) activity without exogenously added pyridoxal-5-phosphate (PLP) was studied in discrete brain nuclei and areas. Repeated injections of haloperidol produced significant changes in GAD activity in the dorsal part of the caudate nucleus, entopeduncular nucleus, pars reticulata of the substantia nigra, lateral hypothalamic area, and dorsomedial hypothalamic nucleus. A reduction of GAD activity after haloperidol was observed in the entopeduncular nucleus and pars reticulata of the substantia nigra. This finding demonstrates biochemically that haloperidol-induced extrapyramidal behavior may be involved in the reduction of GABAergic transmission in the entopeduncular nucleus and pars reticulata of the substantia nigra. A decrease in GAD activity in the lateral hypothalamic area indicates that interaction between GABAergic neurons as well as dopaminergic neurons may be involved in the haloperidol-induced behavioral changes. In addition, close interaction between GABAergic and dopaminergic systems in the dorsomedial hypothalamic nucleus and dorsal part to the caudate nucleus was demonstrated.     

HPLC determination of biogenic amines in discrete brain areas in food deprived rats.

Norepinephrine (NE), dopamine (DA), 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) levels in the lateral hypothalamus (LH), ventromedial hypothalamus (VMH), median raphe (MR) and dorsal raphe (DR) were determined in nondeprived and 48 hr food deprived rats. Simultaneous determination of these compounds was accomplished by means of high performance liquid chromatography (HPLC) with electrochemical detection. When compared with controls, food deprived animals showed significant increases in 5-HT and 5-HIAA levels in the raphe nuclei, significant increases in 5-HIAA in the LH, but no changes in either 5-HT or 5-HIAA levels in the VMH. No changes in catecholamine levels were found in any of the brain areas studied. These results show that indoles in the raphe nuclei, as well as in the LH, are affected by food deprivation. The lack of change in indole levels in the VMH indicates that specific nuclei within the hypothalamus are differentially affected by food deprivation.     

Effect of thymoleptics on fenfluramine-induced depletion of brain serotonin in rats

d,l-Fenfluramine, l-fenfluramine, and l-norfenfluramine produced marked, comparable decreases in brain serotonin. The depletion of brain 5HT induced by fenfluramine was antagonized by chlorimipramine (Cl-IMI) but not by imipramine or desipramine. The effect of Cl-IMI was apparantly not related to major changes in the concentrations of brain fenfluramine or norfenfluramine. This antagonism by Cl-IMI was also observed in 3 different brain areas and at varying time intervals after fenfluramine injection. l-Fenfluramine and l-norfenfluramine were similarly antagonized by chlorimipramine. The anorectic effect of l-fenfluramine was also antagonized by pretreatment with Cl-IMI.The results further support the hypothesis of a direct interaction of fenfluramine with the serotonergic system in the brain.