脓毒性脑病的预警因素分析

目的：研究脓毒性脑病（SE）和无脑病者（NE）的预警因素。方法：分析我院ICU2004．1-2006、9收治的117例脓毒症病人的临床资料及相关检查结果,对比分析两组病人的住院时间、病死率、血培养、血压、白细胞计数（WBC）、血小板计数（PLT）、K＋、Ca2＋、游离钙（iCa2＋）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、白蛋白、球蛋白、总胆红素（TBIL）、直接胆红素（DBIL）、肌酐（SCr）、尿素氮（BUN）、C反应蛋白（CRP）、血糖（BS）、胆固醇、甘油三脂（TG）、PaCO2、CT／MRI、APACHEII评分的差别。结果：52例SE患者的APACHEII评分、病死率、血培养阳性率、ALT、AST、SCr、BUN、PaCO2与65例NE比较差异有统计学意义（P〈0．05）;鲍曼不动杆菌和金黄色葡萄球菌为脓毒症病人感染率最高的革兰阳性菌和阴性菌,分别为18．49％和13．70％,两组感染病原菌和感染率均不一样;10例sE患者头部CT／MRI有微小脓肿和组织水肿等阳性表现,而NE组均无阳性表现;APACHEII评分与脓毒症的病死率相关,相关系数为r=0．541,而且两组病人APACHEII评分不同,病死率也不一样,21-25分段SE组病死率要高于NE组（P=0,001）。结论：APACHEII评分、血培养、ALT、AST、SCr、BUN、PaCO2对诊断和鉴别诊断SE具有重要意义,调整BS、SCr、ALT、BUN、iCa2＋、白蛋白水平对预防脓毒症发生SE有益。     

脓毒性心肌功能障碍

脓毒症是由感染引起的全身炎症反应综合征,证实有感染灶存在或有高度可疑的感染灶。脓毒症是ICU内重症患者的主要死亡原因,且发病率随着年龄的增长而逐渐增加。近十年来,虽然政府在救治脓毒症患者中投入了巨大的资金和技术支持,但源于脓毒症或脓毒性休克患者的病死率仍高达30%~60%。心血管系统在脓毒症与脓毒性休克的病理生理学中扮演着重要着色。过去的四五十年,开展了很多脓毒性心肌功能障碍方面的研究,也积累了不少循证医学证据。然而,心脏只是心血管系统的一部分。诸如脓毒症患者机体血流动力学的变化系脓毒症对心脏的直接效应,还是脓毒症引起心脏前、后负荷及神经体液因素的变化,继而引起心脏继发改变的研究,至今仍在继续。本文概述了近年来脓毒性心肌功能障碍的研究进展,使读者更全面地了解脓毒性心肌功能障碍的病理生理学改变,合理有效地指导脓毒症和脓毒性休克患者的临床救治。     

脓毒性休克治疗新进展

本文回顾了脓毒性休克的治疗三大关键因素：早发现并诊断、早使用抗生素和早期液体复苏,并就抑制炎症因子的释放、抗生素的使用、液体复苏、免疫调理、中医药参与、实施代谢复苏疗法和器官功能的支持治疗等方面进行了系统综述,提出了包括超声在内的组合优化评估和治疗策略仍是目前最为有效,也是明显降低病死率的治疗方式,从而提高救治效果。     

脓毒性休克的诊疗进展

<正>脓毒症是由于感染引起的全身性炎症反应综合征,为大手术术后、严重创伤或感染后常见并发症。脓毒症的发病机制复杂,病理过程涉及炎症、组织损害、凝血功能、免疫等一系列问题~([1]),且与机体多系统、多器官病理生理性改变相关~([2]),常见致病菌为革兰阴性细菌~([3])。脓毒性休克是重症监护室常见危重症,是脓毒症引起的循环功能障碍表现,具有发病急、进展快,且常累及多个脏器,严重威胁患者生命健康,降低患者的生活质量~([4])。近年来,器官功能支持技术及     

兔脓毒性休克模型的建立

目的:建立相对稳定的兔脓毒性休克模型.方法:雄性新西兰大白兔20只,随机分为模型组和假手术组.麻醉后无菌操作下取中、下腹部正中切口,找出盲肠,距盲肠末端8.0cm处4号丝线结扎盲肠和相应血管;于盲肠游离末端避开血管戳孔2次,孔径0.5cm;将盲肠原位放回腹腔,缝合腹壁切口;腹腔内注射30ml/kg温生理盐水.假手术组只探查腹腔.术后每隔3小时监测肛温.颈动脉插管有创动脉压监测确定模型成功后送血培养、血气、血乳酸,监测4小时后处死动物,送腹水培养,取右肺中叶测定肺含水量,取心、肝、脾、肺、肾、肠常规切片HE染色.结果:制模成功时间为:(18.91±1.384)小时;模型平均动脉压MAP(95.00±10.817 vs 52.38±15.565,P＜0.05);血气:PH(7.40±0.047 vs 7.09±0.146,P＜0.01),PCO2(30.0±5.831 vs 19.80±4.104,P＜0.01),BE(-6.46±4.931 vs -24.11±4.276,P＜0.01),HCO3-(18.45±4.367 vs 5.73±2.422,P＜0.01);血乳酸(2.53±1.108 vs 7.85±5.834,P＜0.05);血培养(7/10)阳性:大肠埃希菌;腹水培养(10/10)阳性:大肠埃希菌及阴沟肠杆菌;肛温于术后呈先上升后下降,假手术组肛温较模型组差异有显著性(39.63±0.492 vs 36.82±0.999,P＜0.01);成模后肛温与平均动脉压呈正相关关系,r=0.748.P=0.013,方程:y(平均动脉压)=34.46x+0.45;肺干湿比及肺含水量无明显差异[(0.22±0.014 vs 0.19±0.288,P＞0.05),(78.17±1.375 vs 80.58±2.878,P＞0.05)].常规HE染色可见明显病理学改变.结论:本模型可模拟多微生物感染致脓毒性休克模型,模型相对稳定,可用于兔种属.     

HIV-Tat蛋白神经毒性机制的研究进展

HIV-Tat蛋白是人类免疫缺陷病毒-1型(HIV-1)基因编码的一种被称为反式转录激活因子,是HIV转录和复制所必须的一个很重要的调控蛋白。HIV感染细胞的早期即表达该蛋白,Tat蛋白能够由被感染细胞合成并释放到细胞外,脑脊液和血清中,能改变非感染细胞的结构和功能,特别是对神经元的结构与功能,从而促进艾滋病(AIDS)脑病的发生和发展,也就是说在中枢神经系统,HIV病毒对于神经系统的损伤多为间接损伤,主要依靠其合成蛋白,如Tat蛋白。Tat蛋白进入脑后,可以选择性地对中枢神经细胞产生毒性作用,引起神经元的凋亡,导致中枢神经系统发生病理性改变,如艾滋病痴呆(HAD)和艾滋病相关性脑炎(HIVE),然而HIV-Tat蛋白的神经毒性机制并不完全清楚。本综述将讨论HIV-Tat蛋白神经毒性及其可能的机制,为将来的研究和艾滋病脑病的防治提供更加有利的方向。     

炎症反射的研究进展

以往认为体液调节机制是防止多种促炎因子过量产生的唯一通路,但本世纪伊始新发现了一条生理性的神经性抗炎通路,即炎症反射,而迷走神经则是这一反射的重要载体,免疫细胞上表达的α7nAChR是该反射的"效应器",中枢神经系统也参与了该反射的信号收集、整合与调节的过程.由于这一通路的抗炎作用具有高效、特异性强等特点,其对于治疗炎性疾病具有极其重要的临床应用前景.本文对炎症反射的最新研究进展予以综述.     

量子点细胞毒性及其作用机制

纳米粒子(NPS)在工业和研究中的使用急剧增加,因而这种材料面临一个其潜在毒性的问题。不幸的是,对纳米颗粒与纳米/生物界面可能发生的相互作用没有足够的了解。广大科技工作者正在积极寻求日益关注的纳米技术对人类的影响答案。我们将从NPS在生物媒体中的浓度,尺寸大小,电荷,和配位体的稳定性方面来了解纳米粒子的性质和他们在生物环境中对细胞毒所起的作用;并初步探讨已知的机制,量子点可以破坏细胞,包括氧化应激引起的活性氧(ROS)。微小浓度量子点足以造成长期持久的,甚至是跨代的影响。本文讨论了从纳摩尔到皮摩尔浓度的诱导细胞损伤的量子点(QDS)的浓度,这意味着含镉量子点可以发挥表观遗传毒性,纳米基因毒性,重金属基因的毒性。在此为评估包括量子点的在内的纳米毒性的的纳米材料,我们采用量子点作为一个例证,来阐述以科学为基础的发展到纳米毒理学的相关的问题。     

纳米银神经毒性研究进展

纳米银(sliver nanoparticles,AgNPs)性能优异,在肿瘤的早期诊断和神经系统疾病的诊治中应用广泛.然而纳米颗粒可经多种途径进入中枢神经系统,并可能在神经组织中蓄积,导致神经细胞功能紊乱和神经退行性病变.该综述阐述了纳米银的脑累积效应以及进入中枢神经系统的途径,主要包括嗅神经和血脑屏障途径;阐述了纳...     

基于脑－肠轴理论探讨重症胰腺炎脑损伤“脑病治肠”的科学内涵

胰性脑病（pancreatic encephalopathy,PE）是重症胰腺炎患者病死的主要原因,目前尚无有效治疗手段。临床运用通腑泻下法进行“脑病治肠”的疗效确切,但其现代医学机制尚未完全阐明。肠道菌群与PE脑损伤的发生发展密切相关,且是脑－肠轴的核心通路,可通过迷走神经直接影响脑功能。通腑泻下代表方剂大承气汤可调节中枢神经系统炎症介质的释放,减轻PE脑损伤。以肠道菌群为切入点,从脑－肠轴调控机制的关键环节入手,全面分析肠道菌群构成、功能丰度及优势菌群,观察到胆碱能抗炎通路（cholinergic anti-inflammatory pathway,CAP）的活化程度影响中枢神经系统炎症因子的释放,最终改变PE脑损伤。本文阐述大承气汤通过肠道菌群调节CAP抗中枢神经系统炎症的分子机制,以期为中医以肠道菌群为靶点治疗PE提供理论依据,也为“脑病治肠”提供有力支持。

     

Decreased Plasma and Cerebrospinal Fluid Ascorbate Levels in Patients With Septic Encephalopathy

Septic encephalopathies rapidly affect brain function without the involvement of a specific area causing a broad range of reversible neurologic symptoms. Capillary leakage including dysfunction of the blood-brain barrier has been proposed as a potential pathogenic mechanism in this entity. We tested the hypothesis that oxidative stress measured in plasma and cerebrospinal fluid (CSF) of patients suffering from septic encephalopathy could be linked to the neurologic symptoms of the disease. The neurologic symptoms of eleven patients with septic encephalopathy were described semiquantitatively through a score system. The ascorbate levels were significantly lower in both plasma and CSF from patients with septic encephalopathy than controls, and in CSF but not plasma this decrease correlated with the severity of neurologic symptoms. No significant changes were found for &#102 -tocopherol. Our findings suggest that the short-term oxidative stress may be an important factor in the development of septic encephalopathy, possibly through dysregulation of the blood-brain barrier.     

Neurochemical Mechanisms of Basic Forms of Long-Term Depression of Synaptic Transmission

This review generalizes and analyzes findings available on the neurochemical mechanisms of induction and expression of NMDA-dependent and NMDA-independent forms of homo- and heterosynaptic long-term depression of synaptic transmission in the hippocampus and cerebellum. Neurochemical mechanisms of depotentiation of synaptic transmission are also considered. The role of long-term depression (depotentiation) in the formation of memory traces and learned skills is discussed.     

Neurochemical Mechanisms Underlying Alcohol Addiction: Model Experiments on Rats

We measured the activities of the main alcohol-metabolizing enzymes (alcohol dehydrogenase, AlDH, and aldehyde dehydrogenase, AdhDH) in the blood serum, comparing these indices with the contents of ethanol and its main metabolite, acetaldehyde (AcAdh), in the blood, and also measured the contents of catecholamines (adrenaline, noradrenaline, and dopamine) in the blood and in different brain structures (hypothalamus, midbrain, and neocortex) of rats in the states of acute alcohol intoxication and chronic alcohol addiction. It was shown that, because of dissimilar changes in the activities of AlDH and AdhDH under conditions of alcohol intoxication, the dynamic balance between endogenous ethanol and AcAdh existing in the norm is disturbed, which results in an increase in the level of AcAdh. Such a phenomenon probably is one of the crucial factors underlying the development of alcohol addiction.     

补骨脂酚通过抑制凋亡、氧化应激和炎症反应缓解小鼠脓毒症脑病

目的:探究补骨脂酚能否抵抗小鼠脓毒症脑病。方法:通过小鼠盲肠结扎穿孔法建立脓毒症脑损伤模型。盲肠结扎穿孔后通过腹腔注射补骨脂酚(10 mg/kg)。小鼠随机分为以下4组:假手术(Sham)组;单纯补骨脂酚处理(BAK)组;盲肠结扎穿孔(CLP)组;盲肠结扎穿孔+补骨脂酚处理(CLP+BAK)组。盲肠结扎穿孔48小时后检测脑组织水含量、血脑屏障通透性、凋亡率、IL-1β与TNF-α表达量、MDA含量、SOD与CAT活性。结果:与Sham组相比,CLP组小鼠脑组织水含量(增加21.20%)、脑组织Evans蓝含量(增加237.05%)、凋亡率、MDA含量、IL-1β与TNF-α表达量均明显增高,而SOD与CAT活性明显降低(P0.05)。与CLP组相比,补骨脂酚处理可明显降低脑组织水含量(下降10.94%)、Evans蓝含量(下降39.40%)、凋亡率、MDA含量、IL-1β与TNF-α表达量,而增加SOD与CAT活性(P 0.05)。结论:补骨脂酚通过抑制凋亡、氧化应激和炎症反应,最终减轻脓毒症脑损伤。     

Class I Histone Deacetylase Inhibitor Valproic Acid Reverses Cognitive Deficits in a Mouse Model of Septic Encephalopathy

Accumulating evidence suggests that histone deacetylase inhibitor exert neuroprotective effects in animal models of neurological diseases. We investigated for the first time whether class I histone deacetylase inhibitor valproic acid (VPA) can reverse cognitive deficits in a mouse model of sepsis-associated encephalopathy (SAE). Moreover, the possible mechanisms of protection were also explored. A mouse model of SAE was induced in adult male mice by cecal ligation and puncture (CLP). Mice received an administration of saline or VPA (100 mg/kg) once daily for 14 consecutive days starting either immediately or 2 weeks after operation. Furthermore, the TrkB antagonist K252a was used in another group of experiment to investigate whether brain-derived neurotrophic factor (BDNF)-TrkB signaling pathway is involved in the protection of VPA. Our data suggested that CLP resulted in significant cognitive impairments accompanied by increased expressions in interleukin-1β and caspase-3, and decreased expressions in BDNF, phospho-TrkB (pTrkB), postsynaptic density 95, and synapses, which were reversed by VPA. However, TrkB antagonist K252a abolished the beneficial effects of VPA with regard to cognition and decreased pTrkB expression and synapses in the hippocampus. Taken together, the findings of the present study suggested chronic treatment with VPA reverses cognitive deficits through mechanisms probably via a reduction in inflammation and apoptosis in the brain, as well as the activation of the BDNF-TrkB signaling pathway in a mouse model of SAE.     

The Septic Brain

Sepsis is a major disease entity with important clinical implications. Sepsis-induced multiple organ failure is associated with a high mortality rate in humans and is clinically characterized by pulmonary, cardiovascular, renal and gastrointestinal dysfunction. Recently, several studies have demonstrated that sepsis survivors present long-term cognitive impairment, including alterations in memory, attention, concentration and/or global loss of cognitive function. However, the pathogenesis and natural history of septic encephalopathy and cognitive impairment are still poorly known and further understanding of these processes is necessary for the development of effective preventive and therapeutic interventions. This review discusses the clinical presentation and underlying pathophysiology of the encephalopathy and cognitive impairment associated with sepsis.