高效液相色谱-电喷雾串联四极杆质谱法研究大鼠尿内毛果芸香碱代谢产物

首次应用高效液相色谱-电喷雾串联四极杆质谱法鉴定了大鼠灌胃给予毛果芸香碱0.2mg后0-8小时内尿中的代谢物。4只大鼠给药毛果芸香碱盐酸盐,收集给药后尿液,固相萃取柱富集、然后应用高效液相色谱-电喷雾串联四极杆质谱法在线进行多反应监测,进而对尿中微量的代谢物进行了质谱解析。分别定性为毛果芸香碱的葡萄糖醛酸结合物、毛果芸香酸和毛果芸香酸的葡萄糖醛酸结合物。而且发现了各种代谢产物及原形药物在大鼠体内均有构型变化。     

匹罗卡品诱导的颞叶癫痫小鼠恐惧记忆行为学变化

目的研究匹罗卡品(PILO)诱导的颞叶癫痫小鼠的恐惧记忆行为学变化规律,探讨此行为学检测评价颞叶癫痫的可行性。方法建立PILO小鼠癫痫模型,分PILO注射2周组(n=11)、PILO注射6周组(n=7)和PILO注射10周组(n=11),同时设正常对照组(n=10)。对各组小鼠进行场景恐惧记忆实验,同时进行海马Nissl染色观察。结果经过声音提示恐惧记忆训练,小鼠恐惧记忆的获得受到了损害。场景恐惧记忆测试发现PILO注射2周组小鼠的僵住时间与对照组无统计学差异(P>0.05),而6周组和10周组则显示明显的恐惧记忆减弱(P<0.05);声音提示的恐惧记忆测试发现PILO注射2周组和6周组小鼠僵住时间与对照组无统计学差异(P>0.05),而10周组则出现明显的恐惧记忆减弱(P<0.05)。Nissl染色显示,PILO注射6周和10周组小鼠海马CA3的锥体细胞脱失,排列稀疏,间隙增大,许多细胞胞质中的Nissl小体减少或消失。结论PILO诱导的颞叶癫痫小鼠恐惧记忆的形成及场景恐惧记忆的回忆都受到了损害,但声音提示的恐惧记忆得到了一定程度的保留。恐惧记忆行为学的变化可能会成为评价颞叶癫痫的一个临床指标。     

Sucrose ingestion decreases seizure onset time in female rats treated with lithium and pilocarpine

To extend previous work concerning diet and overt seizures in rats, we tested the hypothesis that ingestion of 10% sucrose-water could reduce seizure onset time (SOT) in rats given lithium and pilocarpine. We found that female but not male rats given free access to a 10% sucrose-water solution for 3 weeks exhibited shorter SOTs than age- and sex-matched control subjects. A separate experiment determined that SOT was significantly reduced whether female rats were provided 1, 2, 3, or 4 weeks of free access to sucrose. Moreover, the daily volume of sucrose ingested was significantly correlated (r=-0.42) with SOT regardless of the duration of sucrose treatment (in weeks). These findings suggest that a diet supplemented with sugar can facilitate the emergence of behavioral seizures in female rats given lithium and pilocarpine. We discuss the potential role of dopamine in mediating the sucrose-induced changes in SOT.     

1%毛果芸香碱脂质体滴眼液对兔眼的缩瞳作用

目的对比研究1%毛果芸香碱脂质体滴眼液与1%毛果芸香碱滴眼液对兔眼的缩瞳作用。方法家兔18只,随机分为实验组、阳性对照组、阴性对照组。实验组应用1%毛果芸香碱脂质体滴眼液,阳性对照组应用1%毛果芸香碱滴眼液,阴性对照组应用空白脂质体滴眼液。各组家兔左眼滴入滴眼液,右眼滴入生理盐水作为空白对照,分别在给药前,给药后0.25、0.5、1、2、3、4、5、7h测量瞳孔直径。结果3组滴药前瞳孔直径左右眼比较,差异无显著性(P>0.05)。滴药后0.25h,阳性对照组缩瞳作用最大(P<0.01),滴药1h瞳孔开始散大,滴药后5h差异无显著性(P>0.05);实验组滴眼后0.5h瞳孔最小(P<0.01),3h瞳孔开始散大,7h差异无显著性(P>0.05);阴性对照组在观察的7h内无差异(P>0.05)。结论1%毛果芸香碱脂质体滴眼液具有缓慢释药,延长作用时间的优点。     

乙酰胆碱、阿托品、毛果芸香碱在痛觉调制中对大鼠蓝斑核神经元形态的影响

目的 研究乙酰胆碱(ACh)、阿托品、毛果芸香碱与正常大鼠蓝斑核(LC)在痛觉调制中的作用及其相互关系.方法 采用电生理学与侧脑室给药的方法,以电脉冲刺激坐骨神经作为伤害性刺激,用玻璃微电极引导LC中痛反应神经元的电变化.观察ACh、阿托品、毛果芸香碱对LC中神经元形态学改变的影响.结果 ACh可使LC内神经元形态发生改变,即神经元体积变大、外形不规则,细胞核轻度水肿等.M受体拮抗剂阿托品能阻断上述作用,使神经元结构基本恢复正常.M受体激动剂毛果芸香碱能产生与ACh相似的效应.结论 外源性ACh不仅能加强大鼠LC中痛反应神经元的电活动,而且使神经元的形态也发生了相应的改变,表现为易化疼痛效应.揭示,ACh的易化疼痛作用主要是通过M受体介导而实现的,LC内神经元形态的改变进一步证实ACh和LC在痛觉调制中起重要作用.     

Structural plasticity of dentate granule cell mossy fibers during the development of limbic epilepsy

Altered granule cell≫CA3 pyramidal cell synaptic connectivity may contribute to the development of limbic epilepsy. To explore this possibility, granule cell giant mossy fiber bouton plasticity was examined in the kindling and pilocarpine models of epilepsy using green fluorescent protein‐expressing transgenic mice. These studies revealed significant increases in the frequency of giant boutons with satellite boutons 2 days and 1 month after pilocarpine status epilepticus, and increases in giant bouton area at 1 month. Similar increases in giant bouton area were observed shortly after kindling. Finally, both models exhibited plasticity of mossy fiber giant bouton filopodia, which contact GABAergic interneurons mediating feedforward inhibition of CA3 pyramids. In the kindling model, however, all changes were fleeting, having resolved by 1 month after the last evoked seizure. Together, these findings demonstrate striking structural plasticity of granule cell mossy fiber synaptic terminal structure in two distinct models of adult limbic epileptogenesis. We suggest that these plasticities modify local connectivities between individual mossy fiber terminals and their targets, inhibitory interneurons, and CA3 pyramidal cells potentially altering the balance of excitation and inhibition during the development of epilepsy. © 2009 Wiley‐Liss, Inc.     

A case of localized adrenergic urticaria mimicking an allergic reaction to a sweat chloride test

Adrenergic urticaria (AU) is a rare type of physical urticaria triggered by stress. It is frequently confused with IgE‐mediated urticaria or other physical urticarias. This report describes a case of localized adrenergic urticaria triggered by a sweat chloride test in an adolescent male with multiple atopic disorders. A pruritic papular rash at the site of a sweat chloride test prompted an evaluation for allergic and physical urticarias using multiple skin test methods. A positive intradermal skin test to noradrenaline, which reproduced the rash observed during the sweat test, lead to the diagnosis of adrenergic urticaria. This is the first case report describing an immediate adrenergic urticarial reaction to sweat chloride testing in a patient with other atopic disorders. Pediatr Pulmonol. 2009; 44:935–938. © 2009 Wiley‐Liss, Inc.     

三种拟胆碱药对兔中枢作用的比较

给兔icv毛果芸香碱,出现抽搐、流涎、咀嚼,脑电呈低幅快波,呼吸兴奋,icv槟榔碱,兔轻度抽搐、流涎,脑电呈双相反应,呼吸兴奋作用短暂;icv氨甲酰甲胆碱,兔亦出现抽搐、流涎、咀嚼及脑电低幅快波反应,但呼吸变化不一,或为加快,或为减慢。提示三种拟胆碱药中枢作用不完全相同,其原因可能与选择性激动中枢不同亚型M受体有关。上述三药均引起心率减慢。     

M3 Cholinoreceptors: New mediator of acetylcholine action on myocardium

Pilocarpine, a nonselective agonist of the muscarinic cholinoreceptors, was shown to activate both M2 and M3 cholinoreceptors in atria under the conditions of microelectrode registration of action potentials in a rat heart. Activation of M3 receptors was demonstrated after selective blocking of M2 receptors with methoctramine (100 nM). This was accompanied by changes in the duration of the action potential and configuration of repolarization phases. The effect was removed by the 4-DAMP selective M3 receptor blocker (10 nM) and also by the inhibition of phospholipase C by U-73122 (1 μM). This suggests that the effects of M3 receptor activation in the atrium are associated, at least partially, with phosphoinositide signaling. Original Russian Text ? D.V. Abramochkin, M.A. Suris, A.A. Borodinova, V.S. Kuzmin, G.S. Sukhova, 2008, published in Neirokhimiya, 2008, Vol. 25, Nos. 1–2, pp. 105–110.