N-乙酰半胱氨酸对犬心房快速起搏电重构的影响

目的:探讨N-乙酰半胱氨酸(NAC)对犬心房快速起搏电重构的影响。方法:取16只犬,随机分为对照组和NAC干预组。NAC组按照15mg/kg/d剂量给予NAC口服6周时间。在犬右房置入电极,快速起搏右心房,诱发房颤并维持2小时。在起搏前后分别测定有效不应期(AERP)。结果:房颤后对照组AERP显著缩短,AERP频率适应性下降(P<0.05);而NAC组房颤前后AERP和AERP频率适应性均无明显变化。结论:在心房快速起搏致房颤2h的模型中,NAC对心房电重构具有明显的保护作用。     

N-乙酰半胱氨酸对犬心房快速起搏电重构的影响

目的：探讨N-乙酰半胱氨酸（NAC）对犬心房快速起搏电重构的影响。方法：取16只犬,随机分为对照组和NAC干预组。NAC组按照15mg／kg／d剂量给予NAC口服6周时间。在犬右房置入电极,快速起搏右心房,诱发房颤并维持2小时。在起搏前后分别测定有效不应期（AERP）。结果：房颤后对照组AERP显著缩短,AERP频率适应性下降（P〈0．05）;而NAC组房颤前后AERP和AERP频率适应性均无明显变化。结论：在心房快速起搏致房颤2h的模型中,NAC对心房电重构具有明显的保护作用。     

N-乙酰半胱氨酸对大鼠心脏成纤维细胞增殖和胶原合成的影响

目的：通过观察N-乙酰半胱氨酸（NAC）对大鼠心脏成纤维细胞（CFs）增殖和胶原合成的影响,探讨NAC对心脏重构的作用。方法：以培养的新生SD大鼠CFs为实验对象,给予不同浓度的NAC进行干预,48小时后用MTT比色法检测CFs增殖水平,用3H脯氨酸掺入法测定总胶原合成。结果：与对照组相比,不同浓度NAC作用下的CFs增殖水平和3H脯氨酸掺入量均比对照组低,且具有浓度依赖性（p〈0.05）。结论：NAC能够抑制SD大鼠CFs增殖,并降低其胶原合成,因此NAC对心脏的病理性重构可能具有保护作用。     

N-乙酰半胱氨酸对大鼠心脏成纤维细胞增殖和胶原合成的影响

目的:通过观察N-乙酰半胱氨酸(NAC)对大鼠心脏成纤维细胞(CFs)增殖和胶原合成的影响,探讨NAC对心脏重构的作用。方法:以培养的新生SD大鼠CFs为实验对象,给予不同浓度的NAC进行干预,48小时后用MTT比色法检测CFs增殖水平,用3H脯氨酸掺入法测定总胶原合成。结果:与对照组相比,不同浓度NAC作用下的CFs增殖水平和3H脯氨酸掺入量均比对照组低,且具有浓度依赖性(p<0.05)。结论:NAC能够抑制SD大鼠CFs增殖,并降低其胶原合成,因此NAC对心脏的病理性重构可能具有保护作用。     

吸入乙酰半胱氨酸对博莱霉素导致的大鼠肺纤维化的影响

目的:研究N-乙酰半胱氨酸(NAC)雾化吸入对于博莱霉素(BLM)导致的大鼠肺纤维化的影响作用。方法:取清洁SD大鼠100只,平均分为10小组,1小组为对照组,其余每3小组为一组,分别为模型组,防治组,治疗组,通过在大鼠气管中注入BLM的方法来制造大鼠肺纤维化模型,防治组在造模前的7天以及造模后的7天内,治疗组在造模后的7天内,分别给予NAC雾化吸入治疗。在成功造模后的第7天、14天、28天,每组处死1小组大鼠,取出病理组织,通过免疫组化方法来观察肺组织纤维化的程度。研究NAC对大鼠肺纤维化的影响。结果:与模型组对比,防治组和治疗组在纤维化程度上明显较轻(P0.05)。结论:吸入NAC对于博莱霉素导致的大鼠肺纤维化有明显的抑制作用,而且防治组疗效明显好于治疗组。既提前7天用药,效果更明显,大鼠获益更多。     

N-乙酰半胱氨酸对脂多糖诱导的急性肺损伤大鼠肺组织病理形态及TGF-β1表达的作用

目的:观察N-乙酰半胱氨酸(NAC)对脂多糖诱导的急性肺损伤大鼠肺组织形态及转化生长因子-β1表达的作用.方法:将30只SD大鼠随机分为正常对照组、模型组和NAC干预组3组,每组10只.模型组经舌下静脉注射5 mg/kg脂多糖制备大鼠急性肺损伤模型,NAC干预组在注射脂多糖后1h腹腔注射NAC(200 mg/kg),注入脂多糖后12h处死大鼠,取左叶肺组织,观察各组大鼠肺组织病理形态和TGF-β1的表达变化.结果:模型组肺泡间隔增宽,腔内有少许出血,渗出及炎性细胞浸润,肺间质充血水肿,有大量炎性细胞浸润,NAC干预组肺部炎性细胞浸润、渗出、出血较模型组明显减轻.模型组肺组织TGF-β1的表达较正常对照组明显增加(P＜0.05),NAC干预组TGF-β1的表达较模型组显著降低(P＜0.05),但与正常对照组比较差异无统计学意义.结论:NAC可显著减轻脂多糖诱导的大鼠急性肺损伤,这可能与其降低肺组织中TGF-β1的表达有关.     

小剂量阿奇霉素联合吸入布地奈德和N-乙酰半胱氨酸治疗特发性肺纤维化的临床疗效分析

目的:观察小剂量阿奇霉素联合吸入布地奈德和N-乙酰半胱氨酸对特发性肺纤维化(IPF)患者肺功能及支气管肺泡灌洗液炎症因子表达的影响。方法:随机将56例确诊为IPF的住院患者分为对照组和治疗组,对照组给予常规治疗,吸氧,戒烟,吸入布地奈德及乙酰半胱氨酸;治疗组在常规治疗基础上加服小剂量阿奇霉素片。动态观察两组患者治疗3、6个月的疗效及肺功能的改善情况;完成2个疗程(6个月)治疗后,检测和比较两组支气管肺泡灌洗液相关炎症因子水平的变化。结果:治疗3个月时,两组患者的动脉血氧分压(PO2)、肺活量(VC)、1秒钟用力呼气容积占预计值百分比(FEV1%pred)、最大通气量占预计值百分比(MVV%pred)、单位肺泡容积的一氧化碳弥散量占预计值百分比(DLCO/VA%pred)均较治疗前显著增加(P0.05);治疗6个月时,治疗组的有效率(20/26,76.9%)明显高于对照组(14/30,46.7%),且PO2、VC、FEV1%pred、MVV%pred及DLCO/VA%pred等肺功能指标均显著高于对照组(P0.05);对照组支气管肺泡灌洗液TNF-α、IL-8浓度均较治疗前降低(P0.05),IL-4、IL-10、IFN-γ浓度较治疗前无明显变化;而治疗组支气管肺泡灌洗液TNF-α、IL-8、IL-4、IL-10浓度均较治疗前降低,IFN-γ浓度较治疗前明显增加(P0.05)。结论:阿奇霉素联合吸入布地奈德和N-乙酰半胱氨酸可能通过改变支气管肺泡灌洗液IFN-γ等炎症因子浓度有效改善IPF患者的肺功能。     

N-乙酰氨基葡萄糖转移酶（OGT）研究进展

O-GlcNAc是一种广泛存在于蛋白质丝/苏氨酸残基上的动态、可逆的蛋白翻译后修饰,它广泛分布在细胞浆和细胞核中,参与调节多种细胞途径。研究表明蛋白的O-GlcNAc糖基化与神经退行性疾病、糖尿病和癌症等疾病相关。在体内,O-GlcNAc动态修饰由N-乙酰氨基葡萄糖转移酶（OGT）和N-乙酰氨基葡萄糖苷酶（OGA）协同完成。近年来,OGT逐渐成为糖生物学领域的研究热点,在其结构、作用机制及晶体学方面取得了快速发展。     

N-乙酰半胱氨酸抗脂多糖诱导的肺动脉损伤的研究

目的 :探讨N 乙酰半胱氨酸 (N acetylcysteine,NAC)减轻脂多糖 (lipopolysaccharide ,LPS)所致的肺损伤及其机制。方法 :应用血管环张力检测技术和扫描电镜方法 ,观察了NAC对LPS引起的肺动脉反应性及肺动脉内皮细胞超微结构变化的影响 ;并测定了肺动脉组织中丙二醛 (malondialhyde ,MDA)、超氧化物歧化酶 (superoxidedismutes ,SOD)及一氧化氮 (nitricoxide,NO)的变化。结果 :LPS(4μg/ml,7h)可降低肺动脉对乙酰胆碱 (ACh)介导的内皮依赖性舒张反应 ,NAC(0 .5mmol/L)可逆转此种反应降低而对正常肺动脉舒缩反应无明显影响 ;NAC可改善LPS引起的肺动脉内皮细胞超微结构损伤并可逆转LPS引起的肺动脉组织中MDA、NO含量增高和SOD活性降低。结论 :NAC可通过抗氧化作用保护肺动脉内皮细胞并增强肺动脉内皮依赖性舒张反应 ,提示此可能是其发挥抗肺动脉压增高从而改善内毒素所致肺损伤的机制之一。     

甲型流感病毒H5N1的系统进化分析简评

美国加州大学Robert G.Wallace,Richard H.Lathrop和Walter M.Fitch等人在2007年3月7日电子版(13日正式出版)的PNAS上发表文章,题目是:甲型流感病毒H5N1的系统进化地理学统计分析学(Astatistical phylogeography of influenza A H5N1)。该文发表以后,国内外流感病毒学者对此发生浓厚的兴趣,提出了一些对该文的评论。采用先进的生物信息学、数学模型等跨学科的先进方法进行病毒学的研究,特别是用来指导传染病预防和控制,是值得提倡和鼓励的,我国科学家应当认真学习;但是任何采用生物信息学方法做出的预测,还须经过病毒学实验研究的验证。以下发表的评述,仅供参考。百家争鸣才有利于科学的进步。     

Potent inhibition of human influenza H5N1 virus by oligonucleotides derived by SELEX

New therapeutics are urgently needed for the treatment of pandemic influenza caused by H5N1 influenza virus mutants. Aptamer was a promising candidate for treatment and prophylaxis of influenza virus infections. In this study, systemic evolution of ligands through exponential enrichment (SELEX) was used to screen DNA aptamers targeted to recombinant HA1 proteins of the H5N1 influenza virus. After 11 rounds of selection, DNA aptamers that bind to the HA1 protein were isolated and shown to have different binding capacities. Among them, aptamer 10 had the strongest binding to the HA1 protein, and had an inhibitory effect on H5N1 influenza virus, as shown by the hemagglutinin and MTT assays. These results should aid the development of new drugs for the prevention and control of influenza virus infections.     

Diagnosis of influenza viruses with special reference to novel H1N1 2009 influenza virus

On 15 April and 17 April 2009, novel swineorigin influenza A (H1N1) virus was identifi ed in specimens obtained from two epidemiologically unlinked patients in the United States. The ongoing outbreak of novel H1N1 2009 influenza (swine influenza) has caused more than 3,99,232 laboratory confi rmed cases of pandemic influenza H1N1 and over 4735 deaths globally. This novel 2009 influenza virus designated as H1N1 A/swine/California/04/2009 virus is not zoonotic swine flu and is transmitted from person to person and has higher transmissibility then that of seasonal influenza viruses. In India the novel H1N1 virus infection has been reported from all over the country. A total of 68,919 samples from clinically suspected persons have been tested for influenza A H1N1 across the country and 13,330 (18.9%) of them have been found positive with 427 deaths. At the All India Institute of Medical Sciences, New Delhi India, we tested 1096 clinical samples for the presence of novel H1N1 influenza virus and seasonal influenza viruses. Of these 1096 samples, 194 samples (17.7%) were positive for novel H1N1 influenza virus and 197 samples (18%) were positive for seasonal influenza viruses. During outbreaks of emerging infectious diseases accurate and rapid diagnosis is critical for minimizing further spread through timely implementation of appropriate vaccines and antiviral treatment. Since the symptoms of novel H1N1 influenza infection are not specifi c, laboratory confi rmation of suspected cases is of prime importance.     

Plasma proteomic analysis of patients infected with H1N1 influenza virus

This study profiled the plasma proteins of patients infected by the 2011 H1N1 influenza virus. Differential protein expression was identified in plasma obtained from noninfected control subjects (n = 15) and H1N1‐infected subjects (n = 15). Plasma proteins were separated by a 2DE large gel system and identified by nano‐ultra performance LC‐MS. Western blot assays were performed to validate proteins. Eight plasma proteins were upregulated and six proteins were downregulated among 3316 plasma proteins in the H1N1‐infected group as compared with the control group. Of 14 up‐ and downregulated proteins, nine plasma proteins were validated by Western blot analysis. Putative protein FAM 157A, leucine‐rich alpha 2 glycoprotein, serum amyloid A protein, and dual oxidase 1 showed significant differential expression. The identified plasma proteins could be potential candidates for biomarkers of H1N1 influenza viral infection. Further studies are needed to develop these proteins as diagnostic biomarkers.     

重配技术构建高产H1N1型流感疫苗病毒株

目的以经典重配技术制备高产H1N1流感疫苗病毒株。方法以野生型A1/云南昆明/03/2009(H1N1)作为HA及NA基因的供体株,以WHO疫苗株A/Perth/16/2009(H3N2)作为高产基因供体株,共同感染SPF鸡胚,经抗H3及抗N2血清中和筛选法及终末稀释法筛选高产重配H1N1病毒。结果获得一株重配H1N1流感病毒株,病毒血凝滴度为1∶4 096,病毒滴度为7.8 lg EID50/mL,显示为鸡胚高产病毒株;血凝抑制结果为1∶1 024,单向免疫扩散试验结果为阳性,证明抗原性与野生株一致;基因测序结果表明重配株的HA及NA基因序列与野生株序列一致。结论构建了高产重配H1H1流感疫苗病毒株,并应用经典重配技术建立了制备高产流感疫苗病毒株的技术平台。     

甲型H1N1流感病毒佐剂疫苗小鼠免疫效果

为了探讨甲型H1N1流感病毒氢氧化铝佐剂疫苗对小鼠的免疫作用及对小鼠繁殖性能的影响,以不同剂量、不同免疫程序免疫小鼠后定期采血;用血凝抑制(HI)方法检测血清H1N1流感病毒HI抗体滴度,观察H1N1流感病毒佐剂疫苗对小鼠受孕、产仔、哺乳的影响;比较孕鼠及非孕鼠的抗体滴度,免疫后孕鼠所产仔鼠的体重及H1N1胎传抗体水平。结果显示,以0.5μg组开始的不同剂量、不同免疫程序均可使小鼠产生90倍以上水平的H1N1流感病毒抗体;免疫后的小鼠不影响受孕、产仔及哺乳;仔鼠保护性抗体可持续1个月以上。H1N1流感病毒佐剂疫苗是一种高免疫原性的制剂,用低剂量免疫,即可产生90倍以上持续时间较长的保护性抗体。这种佐剂疫苗对小鼠的繁殖性能无明显影响,免疫产生的抗体经胎盘可垂直传递给仔鼠。     

Characterization of a highly pathogenic avian influenza H5N1 virus isolated from an ostrich

The continued spread of a highly pathogenic avian influenza (HPAI) H5N1 virus among poultry and wild birds has posed a potential threat to human public health. An influenza pandemic happens, when a new subtype that has not previously circulated in humans emerges. Almost all of the influenza pandemics in history have originated from avian influenza viruses (AIV). Birds are significant reservoirs of influenza viruses. In the present study, we performed a survey of avian influenza virus in ostriches and H5N1 virus (A/Ostrich/SuZhou/097/03, China097) was isolated. This H5N1 virus is highly pathogenic to both chickens and mice. It is also able to replicate in the lungs of, and to cause death in, BALB/c mice following intranasal administration. It forms plaques in chicken embryo fibroblast (CEF) cells in the absence of trypsin. The hemagglutinin (HA) gene of the virus is genetically similar to A/Goose/Guangdong/1/96(H5N1) and belongs to clade 0. The HA sequence contains multiple basic amino acids adjacent to the cleavage site, a motif associated with HPAI viruses. More importantly, the existence of H5N1 isolates in ostriches highlights the potential threat of wild bird infections to veterinary and public health.     

一株2011年出现的季节性甲型H1N1流行性感冒病毒血凝素基因特性的研究

本文通过比较2011年分离培养的1株季节性甲型H1N1流行性感冒(简称流感)病毒(A/Shanghai/1167/2011(H1N1))与历年季节性甲型H1N1流感病毒的血凝素(HA)基因,追溯该病毒的基因变异与来源,探讨该毒株的出现对流感防控工作的意义.采用反转录-聚合酶链反应(RT-PCR)方法扩增病毒的HA和神经氨酸酶(NA)片段,并进行测序;应用分子生物学软件对获得的序列进行分析,绘制基因进化树;同时,通过血凝抑制试验检测2011年下半年健康人群中该流感病毒的抗体水平.结果显示,A/Shanghai/1167/2011(H1N1)的HA基因序列与世界卫生组织(WHO)2007～2008年季节性甲型H1N1流感病毒疫苗株A/Brisbane/59/2007(H1N1)最接近,同源性达99.2%,与新型甲型H1N1流感病毒A/California/07/2009疫苗株同源性仅为72.4%.其HA基因裂解位点为PSIQSR↓GLF,尚未出现高致病性的分子特征.HA片段共编码557个氨基酸,有9个潜在的糖基化位点,序列与2009年前WHO疫苗株A/NewCaledonia/20/1999(H1N1)、A/SolomonIslands/3/2006(H1N1)和/Brisbane/59/2007(H1N1)相比,分别有15、12和4处不同,这些差异分布在Sa、Sb、Ca1、Ca2、Cb 5个抗原决定簇的氨基酸差异分别有5、5和2处.该毒株在健康人群血清的抗体阳性率为34.33%,几何平均效价(GMT)为10.38.A/Shanghai/1167/2011(H1N1)是2011年出现在上海地区的一个季节性甲型H1N1流感病毒毒株,其抗原变异与既往季节性甲型H1N1流感病毒相比不大,但在以A(H1N1)pdm09为主要流行株的年份检测到散在发生的既往季节性甲型H1N1流感病毒毒株应当引起重视,其在人群中的抗体水平较低,易引起流行,需要提高对类流感人群中此种毒株的持续监测.     

H5N1亚型禽流感病毒进化的研究进展

由H5N1流感病毒引起的高致病性禽流感,在禽类之间广泛传播。当人类接触这些禽类时,可能会被感染并产生严重的呼吸道症状,且死亡率高达60%。血凝素(hemagglutinin,HA)是H5N1病毒中和抗体的主要抗原,为了便于对病毒的HA突变进行研究,根据HA遗传基因的差异远近,所有的H5病毒株都被划分在20个分支内。对于H5N1病毒进化的研究在禽流感疫苗的研制、禽流感大流行的预防等方面均具有重要意义。现对禽流感、H5N1病毒特征、血凝素的结构功能、H5N1病毒的分支以及病毒进化的研究进行概述。     

Functional association between influenza A (H1N1) virus and human

Influenza A (H1N1) virus is a severe threat worldwide. It is important to gain a better understanding of the mechanism of the infection. In the paper, we established a computational framework to investigate the crosstalk between the virus and the host, by finding out the proteins that the virus is attacking. The targeted proteins were predicted by taking human proteins laid on the same GO functions or processes as the virus proteins. One hundred and one core proteins were identified. The results provide some knowledge of the possible biological processes and molecular interactions caused by the viral infection, including the host responses.     

Discovery and synthesis of novel benzofurazan derivatives as inhibitors of influenza A virus

The identification of a novel hit compound inhibitor of the protein–protein interaction between the influenza RNA-polymerase PA and PB1 subunits has been accomplished by means of high-throughput screening. A small family of structurally related molecules has been synthesized and biologically evaluated with most of the compounds showing micromolar potency of inhibition against viral replication.