Antagonistic influences of dibutyryl cyclic AMP and dibutyryl cyclic GMP on the beating rate of cultured mouse myocardial cells.

Cultured myocardial cells obtained from neonatal mouse ventricles beat spontaneously and rhythmically. Norepinephrine and dibutyryl cyclic AMP accelerated the rate of spontaneous beating. Dibutyryl cyclic GMP slightly decreased the rate of spontaneous beating. The acceleration of the beating rate of cultured myocardial cells by norepinephrine or dibutyryl cyclic AMP was counteracted by dibutyryl cyclic GMP. Preincubation of cultured myocardial cells with dibutyryl cyclic GMP prevented the positive chronotropic effect of dibutyryl cyclic AMP.     

痛情绪相关神经递质及神经环路研究进展＊

痛情绪是指因疼痛引发的情绪和情感体验，是疾病过程中最常见的一种情绪。痛情绪相关神经机制非常复杂，但主要与单胺类神经递质、神经肽和某些神经环路有关，笔者将结合目前研究现状分别从以上两方面展开，就痛情绪相关单胺类神经递质和神经肽在受体分类、脑区通路、共疾病以及各神经递质之间的联系和痛情绪相关神经环路中各个蛋白的作用机制等方面进行探讨。     

损毁大鼠中枢去甲肾上腺素能系统对海马CA3区突触形态的影响

目的:观察中枢去甲肾上腺素(NE)与海马突触形态之间的关系。方法:通过6-OHDA损毁大鼠双侧背去甲肾上腺素束来建立海马内去甲肾上腺素能系统损伤大鼠模型,于建模前后对其进行迷宫检查及类P3测定,然后对大鼠海马CA3区多形层突触界面的结构参数进行定量分析。结果:突触后膜致密物质厚度明显变薄,突出界面曲率减小、穿孔性突触的比例也有不同程度降低,突触间隙宽度加大。结论:海马内NE的正常水平对维持突触界面超微结构是必要的。     

Adaptive Predictive Control of Arterial Blood Pressure Based on a Neural Network During Acute Hypotension

In acute hypotension, an automated drug infusion system to control mean arterial blood pressure (MAP) has not been previously studied, though many investigations have examined the use of vasodilating drugs to control MAP in postoperative hypertension. Therefore, we examined an automated control of MAP during acute hypotension using a neural network (NN) approach. A proportional-integral-derivative (PID) control, an adaptive predictive control using a NN (APC(NN)), a combined control of APC(NN) and PID (APC(NN-PID)), a fuzzy control, and a model predictive control were tested in computer simulation based on the MAP response to norepinephrine (NE) of 25 microg ml(-1). In six anesthetized rabbits, using the NE of 25 microg ml(-1), the PID control, APC(NN), and APC(NN-PID) prevented severe hypotension compared to an uncontrolled condition. Under PID control, four of the six animals showed MAP oscillation. Using NE of 50 microg ml(-1), the rabbits recovered from acute hypotension for all systems tested but showed sustained MAP oscillation during PID control. In conclusion, utilization of a NN for adaptive predictive control systems could facilitate the development of an automated drug infusion apparatus because it provides robust control even when acute or large perturbations and inter-individual differences in the sensitivity to therapeutic agents occur.     

Hypothalamic and hindbrain NPY, AGRP and NE increase consummatory feeding responses

Feeding behavior is comprised of both appetitive and consummatory responses to food. Appetitive responses include the motivated acquisition of food. Consummatory responses, including swallowing, are those that move the food from the mouth to the stomach. Intraoral delivery of liquid food bypasses the requirement for appetitive responses and has been used to examine consummatory responses directly in intact rats. In the present study, we administered neuropeptide Y (NPY), agouti-related protein (AGRP) and norepinephrine (NE), into the paraventricular nucleus of the hypothalamus (PVN) or into the fourth cerebral ventricle to examine their effects on the consummatory component of feeding behavior in the rat. To measure consummatory responses, milk (40% lactose free cow's milk diluted with water) was infused intraorally through a chronic cheek fistula (1 ml/min), using an alternating 5 min on − 1 min off schedule, until rejection occurred. We found that both hypothalamic and fourth ventricle injections of NPY, AGRP and NE significantly increased consumption of the intraorally-delivered milk. Our results indicate that the circuitry for modulation of consummatory ingestive responses includes NE, NPY and AGRP receptors operating in both hypothalamic and hindbrain sites.     

大鼠冠状动脉平滑肌细胞电活动的实验研究

应用先进技术细胞内微电极的方法研究了大鼠冠状动脉平滑肌细胞的静息膜电位 (Em)及其对血管活性物质KCl、ACh、NE的反应性。结果表明 ,大鼠冠状动脉平滑肌细胞静息膜电位稳定 ,其均值为 -54.38± 2 .36mv ,KCl和ACh均可引起膜电位去极化 ,且呈剂量依赖式特点 ;NE对膜电位无明显影响。结论　同一动物的不同血管或不同动物的同一血管反应性存有明显的异质性。     

Different quantitative EEG alterations induced by TBI among patients with different APOE genotypes

It has been well established that aging is the most prominent risk factor for PD. In the MPTP mouse model which has been widely used to study PD, studies have shown that MPTP exhibits its neurotoxic effects on the dopaminergic system in an age-dependent manner. Although it is recognized the serotonergic system is impacted in PD, how aging influences serotonergic neurodegeneration in PD has not been adequately investigated. In the present studies, we examined the long-term effects of MPTP treatment on regional concentrations of dopamine (DA), serotonin (5-HT) and norepinephrine (NE) in the striatum and prefrontal cortex (PFC). We also determined if there are differences in the age-dependent vulnerability of the monoaminergic system to MPTP. In young (3-month-old) mice, MPTP produced significant decreases in striatal DA but no changes in striatal 5-HT and NE three weeks after MPTP treatment. There was partial recovery of striatal DA concentrations 18 months later. This was accompanied by elevated striatal 5-HT. In the PFC, NE was decreased but there was complete recovery 18 months later. By contrast, we observed a long-term decrease in prefrontal 5-HT with no recovery of 5-HT concentrations 18 months after MPTP treatment. Striatal DA and NE but not 5-HT neurons exhibited age-dependent vulnerability to MPTP. Aging had no influence on the neurotoxic effects of MPTP in the PFC. Thus, there is divergence in the response of DA and 5-HT systems to MPTP neurotoxicity.     

Rats subjected to chronic-intermittent hypoxia have increased density of noradrenergic terminals in the trigeminal sensory and motor nuclei

Rodents subjected to chronic intermittent hypoxia (CIH) are used to investigate the mechanisms underlying the consequences of the obstructive sleep apnea (OSA) syndrome. Following CIH, rats have an increased density of noradrenergic terminals in the hypoglossal motor nucleus which innervates lingual muscles that protect the upper airway from collapse in OSA patients. Here, we investigated whether such an increase also occurs in other brainstem nuclei. Six pairs of male Sprague-Dawley rats were exposed to CIH or sham treatment for 10 h/day for 35 days, with O₂ level oscillating between 24% and 7% every 3 min. Brainstem sections were immunohistochemically processed for dopamine-β-hydroxylase, a marker for norepinephrine. Noradrenergic terminal varicosities were counted in the center of the trigeminal motor nucleus (Mo5) and the interpolar part of the spinal trigeminal sensory nucleus (Sp5). In the Mo5, noradrenergic varicosities tended to be 9% more numerous in CIH- than sham-treated rats, and in the Sp5 they were 18% more numerous in CIH rats (184 ± 9 vs. 156 ± 8 per 100 × 100 μm counting box; p = 0.03, n = 18 section pairs).These data suggest that CIH elicits sprouting of noradrenergic terminals in multiple motor and sensory regions of the lower brainstem. This may alter motor and cardiorespiratory outputs and the transmission of cardiorespiratory and motor reflexes in CIH rats and, by implication, in OSA patients.     

不同喉镜气管插管时的血流动力学比较

目的比较靶控诱导后Shikani喉镜、Macintosh直接喉镜和GlideScope视频喉镜插管时的应激反应。方法选取2008年12月-2009年2月期间ASAⅠ～Ⅱ级、拟于全身麻醉下行择期颅内占位病变切除术的患者30例,随机分为Shikani喉镜组（S组）、Macintosh直接喉镜组（M组）与GlideScope视频喉镜组（G组）。靶控异丙酚和瑞芬太尼诱导,分别采用上述3种喉镜行经口气管插管。记录患者的心率、血压,计算心率收缩压乘积（RPP）。结果 3组插管时间、心率、血压和RPP比较差异无统计学意义（P〉0.05）。S组和M组插管后心率、血压及RPP均较插管前显著升高（P〈0.05）,而G组插管后的心率、60～300s时的收缩压、平均动脉压和RPP与插管前比较,差异无统计学意义（P〉0.05）。结论 3种喉镜进行经口气管插管时具有相似的血流动力学反应,GlideScope视频喉镜更有利于循环稳定。     

去甲肾上腺素减轻脂多糖所致内皮细胞损伤

目的:探讨去甲肾上腺素(norepinephrine,NE)减轻脂多糖(lipopolysaccharides,LPS)对内皮细胞损伤的作用。方法:用100 mg/L LPS诱导人脐静脉血管内皮细胞HUVEC-12损伤,用不同浓度NE处理后,使用realtime PCR及Western blot法检测各组内皮细胞血管内皮型钙黏素(VE-cadherin)表达的变化,ELISA法测定细胞培养上清液中TNF-α、IL-1β、IL-2和IL-10的浓度,活性氧簇(reactive oxygen species,ROS)检测试剂盒检测细胞内的ROS水平。结果:LPS可显著抑制内皮细胞中VE-cadherin m RNA和蛋白的表达水平,同时伴有TNF-α、IL-1β和IL-2升高及IL-10下降,ROS含量明显增加;不同浓度的NE呈剂量依赖性地上调VE-cadherin的m RNA和蛋白表达,减轻细胞内的氧化应激水平,并部分逆转TNF-α、IL-1β、IL-2和IL-10的变化。结论:不同浓度NE能明显逆转LPS造成的内皮细胞损伤,其机制可能与上调VE-cadherin、减轻细胞的氧化应激及炎性介质水平有关。