星形胶质细胞与认知功能

星形胶质细胞是中枢神经系统中数量最多的一类胶质细胞,不仅为神经元提供能量和代谢的支持,而且在形成和维持血脑屏障、调节突触可塑性等方面发挥重要作用.尤其是在以认知功能障碍为主要表现的神经退行性疾病的发生发展过程中发挥了神经损伤和保护的双重作用.本文结合近年来研究,从生理和病理调节两个方面综述星形胶质细胞对机体认知功能的影响.     

腺苷蛋氨酸治疗药物性肝损害52例疗效观察

目的观察两种疗程的腺苷蛋氨酸对药物性肝损害的疗效。方法 52例药物性肝损害患者,分为两组,A组28例予以腺苷蛋氨酸,2.0 g/d,疗程4周;B组24例予以5%葡萄糖500 ml+腺苷蛋氨酸每天2.0 g,疗程2周,其后继续使用常规保肝药物至4周。两组患者基线指标具有可比性,观察患者肝功能指标ALT、AST、TBil、DBil、r-GT、ACP、TBA的变化。结果治疗2周时,2组患者肝功能指标与治疗前ALT、AST、TBil、DBil相比差异有统计学意义(P<0.05),但2组间比较无差异;治疗4周时,肝功能指标明显改善,与基线及2周组患者相比ALT、AST、TBil、DBil差异均有统计学意义(P<0.05)。结论腺苷蛋氨酸在治疗药物性肝损害上有较好疗效,4周的疗效明显高于2周。延长治疗周期,以4周为1个疗程可以在临床取得更好的疗效。     

Fas/Fas配体系统及其下游信号转导通路的激活促进酒精性肝炎及酒精性肝纤维化的进展

目的 探明Fas/Fas配体(FasL)系统及其主导信号转导通路在酒精性肝炎和肝纤维化发生、发展中的作用及其机制. 方法 C57BL/6J小鼠以含4％(V/V)乙醇的Lieber-DeCarli液体饲料喂养4周,自第5周起联合微量CCl4腹腔注射至第8周,分别建立酒精性肝炎和肝纤维化模型.脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测肝细胞凋亡.分别采用逆转录-聚合酶链反应、westem blot及免疫组织化学染色检测肝组织Fas、FasL、天冬氨酸特异性半胱氨酸蛋白酶3(caspase3)及细胞色素P450 2E1(CYP 2E1)的mRNA及蛋白质表达.多组样本均数间差异比较用单因素方差分析或Kruskal-Wallis H检验,组间比较用LSD-t检验或Mann-Whitney U检验. 结果 应用含4％(V/V)乙醇的Lieber-DeCarli液体饲料联合微量CCl4腹腔注射可快速建立小鼠酒精性肝炎和肝纤维化模型.肝细胞凋亡数随肝脏炎症及纤维化的加重而增高,并伴有凋亡相关基因表达增强.对照组、酒精性肝炎组、酒精性肝纤维化组小鼠细胞凋亡相关基因表达水平依次升高:Fas mRNA的相对表达量分别为0.50±0.05、0.61±0.10、0.76±0.03(H=12.137 P＜0.05),Fas蛋白的相对表达量分别为0.52±0.14、0.86±0.10、0.99±0.09(F=12.758P＜0.01);FasL mRNA相对表达量分别为0.31±0.03、0.53±0.02、1.02±0.04(F=153.260 P＜0.01);caspase3mRNA对表达量分别为0.86±0.11、0.85±0.05、1.33±0.16(F=8.740,P＜0.01),caspase 3蛋白相对表达量分别为0.40±0.03、0.69±0.06、1.02±0.10(F=90.785,P＜0.01);CYP 2E1 mRNA相对表达量分别为0.72±0.14、1.00±0.15、1.30±0.20(H=4.713,P＜ 0.01);各组间比较,P值均＜0.05.免疫组织化学染色结果显示,FasL及CYP 2E1的蛋白与mRNA的表达趋势一致. 结论 Fas/FasL系统及其下游信号转导通路的激活可能是酒精性肝病中诱导肝细胞凋亡的主导因素,可进一步促进酒精性肝炎和肝纤维化的发生与进展.     

LC-MS法测定人血浆中人参三醇二琥珀酸酯钠含量的方法学研究

目的：建立测定人血浆中人参三醇二琥珀酸酯钠的液相色谱-质谱联用法。方法：色谱柱为Shimadzu VP-C₁₈柱（150 mm×2.0 mm,5 μm）; 乙腈-10 mmol/L乙酸铵水溶液（55∶45）为流动相,体积流量0.3 mL/min;柱温40 ℃;内标物吲达帕胺。质谱条件为电喷雾离子源（ESI）,选择负离子提取方式检测,人参三醇二琥珀酸酯钠和吲达帕胺的选择检测离子分别为m/z 675.5（[M-Na+H] ⁺）、m/z 364.1（[M+H] ⁺ ）。结果：人参三醇二琥珀酸酯钠线性范围为0.030 4～101.3 μg/mL,定量下限为0.030 4 μg/mL。准确度、精密度以及稳定性均符合有关要求。结论：本方法专属性强,灵敏度高,适用于人血浆中人参三醇二琥珀酸酯钠的药代动力学研究。     

PET/CT无创检测实验性动脉粥样硬化斑块的初步研究

目的 探讨PET/CT无创检测动脉粥样斑块的可行性.方法 6只新西兰大白兔随机分成实验组和对照组.实验组通过球囊拉伤膈下降主动脉内膜,并饲喂含2%胆固醇的高脂饲料20周,制造动脉粥样硬化模型;对照组仅饲喂普通饮食20周.静脉注射FDG(1 mCi/kg)180 min后,将对照组和实验组动物置于PET/CT设备下进行降主动脉活体成像,之后处死实验组动物,进行降主动脉标本游离,数码照相,降主动脉标本分段,测定其放射强度和靶非靶比值.结果 注药180 min后18F-FDG PET/CT活体显像显示:所有实验性动脉粥样硬化兔均可见沿降主动脉分布的放射性浓集显像.离体大体标本数码照相病变斑块与活体显像相一致.活体SUV以及离体标本放射性技术显示靶-非靶比值均相对较高.结论 18F-FDG PET/CT无创检测动脉粥样斑块具有一定的可行性,有可能发展成为一种临床无创评价斑块稳定性的方法.     

Reinforcement enhancing effect of nicotine and its attenuation by nicotinic antagonists in rats

Rationale Recent studies have demonstrated that nicotine can enhance operant responding for other nonpharmacological reinforcing stimuli. However, the nature of the reinforcement-enhancing effect of nicotine remains largely unknown. Objective The present study determined the dose dependency of the ability of nicotine to increase lever-pressing responses maintained by a compound visual stimulus (VS) in rats and examined its sensitivity to pharmacological antagonism of nicotinic acetylcholine receptors (nAChRs). Materials and methods Male Sprague–Dawley rats were trained in daily 1-h sessions to lever press for delivery of a VS (1 s lever light on and 60 s house light off) on a fixed ratio 5 schedule. During these sessions, eight scheduled response-independent intravenous infusions of nicotine (total amount: 0, 0.06, 0.12, 0.24, 0.48 mg kg⁻¹ h⁻¹) were delivered. In pharmacological tests, a nonselective nAChR antagonist mecamylamine, α4β2-selective antagonist dihydro-β-erythroidine (DHβE), and α7-selective antagonist methyllycaconitine (MLA) were administered in different groups of rats 30 min before the session. Results The VS maintained a moderate level of lever-pressing responses and nicotine dose-dependently increased responses for the VS presentations. Preteatment of mecamylamine and DHβE but not MLA significantly attenuated the nicotine-enhanced responding. However, mecamylamine had no effect on responding for the VS in rats that received scheduled saline infusions. Conclusions These results demonstrate dose dependency of the reinforcement-enhancing effect of nicotine and suggest that activation of the α4β2- but not α7-containing nAChRs may mediate this effect.     

Self-administered and noncontingent nicotine enhance reinforced operant responding in rats: impact of nicotine dose and reinforcement schedule

Rationale Nicotine infusions that are self-administered (contingent) or response-independent (noncontingent) increase lever pressing for a reinforcing nonpharmacological stimulus in rats, suggesting that in addition to primary reinforcement, nicotine self-administration may result from nicotine enhancing the reinforcement derived from nonnicotine stimuli. Objectives Based on our previous research, in this study, we tested the hypothesis that contingent and noncontingent nicotine would equally elevate responding for a moderately reinforcing visual stimulus, across a range of nicotine doses on both fixed ratio and progressive ratio reinforcement schedules. Materials and methods The rats lever pressed for a visual stimulus with contingent nicotine, noncontingent nicotine, or contingent saline. Separate groups responded for saline or nicotine without the visual stimulus. Three doses of nicotine (0.01, 0.03, and 0.09 mg/kg per infusion, free base) were tested in a between-groups design. After responding on an escalating fixed ratio reinforcement schedule, the rats were tested on a progressive ratio schedule. Results Compared to responding for the visual stimulus with saline, both contingent and noncontingent nicotine equally elevated lever pressing for the stimulus at each dose on fixed and progressive ratio schedules. In the absence of the stimulus, only the highest nicotine dose sustained self-administration. Conclusions The ability of noncontingent nicotine to elevate responding for a moderately reinforcing visual stimulus occurs across a range of doses, and both self-administered and noncontingent nicotine equally increase motivation to obtain the stimulus, as reflected by performance on a progressive ratio schedule. In the absence of a contingent stimulus, primary reinforcement from nicotine only supports self-administration at high nicotine doses in rats.     

慢性乙型肝炎患者外周血单个核细胞内HBV-DNA与中医证型关系的研究

目的探讨慢性乙型肝炎患者血清乙肝病毒脱氧核糖核酸（HBV—DNA）及外周血单个核细胞（PBMCs）中HBV．DNA感染与中医证型的关系。方法220例慢性乙型肝炎患者进行乙肝标志物检查、血清HBV—DNA（定量）及PBMCs中HBV—DNA检测（PCR方法）,经中医辨证确定205例患者的中医证型。结果研究发现各中医证型血清HBV—DNA（定量）≥1．0×10^5拷贝／mL（高病毒栽量）患者比例由小到大排列依次为：湿热中阻证〈瘀血阻络证〈肝肾阴虚证〈脾肾阳虚证〈肝郁脾虚证。肝郁脾虚证组血清HBV—DNA（定量）≥1．0×10^5拷贝／mL患者比例最高（占82．5％）,与湿热中阻证组（占55．2％）差异有显著性（P〈0．01）。各中医证型PBMCs中HBV—DNA感染患者比例由小到大排列依次为：肝肾阴虚证〈湿热中阻证〈脾肾阳虚证〈瘀血阻络证〈肝郁脾虚证。肝郁脾虚证组PBMCs中HBV．DNA感染患者比例最高（占77．2％）,与肝肾阴虚证（占27．3％）、湿热中阻证（占34．3％）、瘀血阻络证（占53．1％）比较,差异均有显著性（P〈0．01）。结论血清HBV—DNA（定量）及PBMCs中HBV—DNA感染与中医证型之间有一定关系,肝郁脾虚证组血清HBV．DNA（定量）≥1．0×10^5拷贝／mL患者比例及PBMCs中HBV—DNA感染患者比例最高,治疗应注重扶正祛邪。     

发现1株携带多种β-内酰胺类、氨基糖苷类耐药基因的鲍氏不动杆菌

目的 分析多药耐药鲍氏不动杆菌对β-内酰胺及氨基糖苷类抗菌药物耐药的原因.方法 用三维试验分析多药耐药鲍氏不动杆菌临床菌株所产β-内酰胺酶,并进行初步分类,用聚合酶链反应(PCR)扩增和产物测序方法确认β-内酰胺酶及氨基糖苷类基因,用基因测序证实基因型.结果 该临床菌株产超广谱β-内酰胺酶及AmpC酶,经分子生物学方法证实同时存在TEM、OXA-23、ADC基因型;并同时存在氨基糖苷类aac(3)-Ⅰ、aac(6')-Ⅰb和ant(3")-Ⅰ基因.结论 发现1株同时存在TEM、OXA-23、ADC、aac(3)-Ⅰ、aac(6')-Ⅰb和ant(3")-Ⅰ基因的鲍氏不动杆菌.