牛珀至宝微丸对内毒素休克肾组织诱生型一氧化氮合酶表达的影响

目的　探讨牛珀至宝微丸对内毒素休克肾组织iNOS表达的作用。方法　静脉注射内毒素 (LPS) 1 5mg/kg、腹腔注射D 氨基半乳糖糖 (D Ga1N) 10 0mg/kg造成内毒素休克模型 ,用牛珀至宝微丸干预处理 ,免疫组化方法检测诱生型一氧化氮合酶 (iNOS)在肾组织内的表达。结果　牛珀至宝微丸可以使肾内iNOS表达减弱 ,肾损伤减轻。结论　牛珀至宝微丸可以减轻内毒素休克造成的肾损伤 ,这种保护作用可能是通过调节肾组织NOS表达而产生的     

转录因子NF-κB在内毒素休克中的作用

目的探讨内毒素休克大鼠组织炎性介质的表达特征及其和核转录因子NFκB(nuclearfactorkappaB)的关系。方法应用免疫组织化学技术检测脂多糖(lippolysaccharice,LPS)内毒素休克大鼠肝肾组织转录因子NFκB、炎性介质ICAM1、VCAM1、iNOS的表达。结果LPS内毒素休克大鼠肝肾组织转录因子NFκBp65,炎性介质ICAM1、VCAM1、iNOS阳性细胞率高于正常对照组;炎性介质ICAM-1、VCAM-1、iNOS阳性细胞率与NF-κBp65阳性细胞率成正相关。用吡咯烷二硫氨基甲酸(pyrrolidinedithiocarbmate,PDTC)抑制转录因子NFκB的内毒素休克大鼠炎性介质ICAM1、VCAM1、iNOS阳性细胞率低于LPS组。结论核转录因子NFκB在LPS引起的大鼠内毒素休克炎性介质的表达中起调节作用。     

核转录因子-κB与支气管哮喘的研究进展

近年来,支气管哮喘发病率呈逐年上升趋势,有效控制哮喘的发生对哮喘患者的生活质量至关重要.目前研究认为气道炎症和气道重构是支气管哮喘病理过程的两个重要方面.此过程与多种炎性蛋白的高表达有关,而核转录因子-κB(NF-κB)作为这些炎症蛋白的上游调控因子参与了哮喘的病理发展.由此,特异性的抑制NF-κB信号转导通路为支气管哮喘的治疗开辟了一条新的途径.     

肾癌病理组织中核转录因子κB的表达及其意义

目的：探讨核转录因子κB（NF-κB）表达在肾癌发生、发展中的意义。方法：采用免疫组化方法检测66例肾癌病理标本（肾癌组）中NF-κB的表达情况,并与40例非癌肾组织病理标本（对照组）中NF-κB的表达情况比较。结果：肾癌组NF-κB阳性表达率为75.8%,对照组NF-κB阳性表达率为15.0%,肾癌组明显高于对照组（P〈0.05）。NF-κB的表达与肾癌病理组织学分级之间无明显的相关性（P〉0.05）;NF-κB的表达与肾癌的TNM分期之间呈显著的正相关（P〈0.05）。结论：肾癌病程中存在NF-κB的异常激活,NF-κB的表达与肾癌病理组织学分级之间无明显的相关性;NF-κB的表达与肾癌的TNM分期之间呈显著的正相关关系。     

β-连环蛋白和核转录因子-κB在大肠癌中的表达及临床意义

β-连环蛋白(β-cat)和核转录因子-κKB(NF-κB)分别作为Wnt信号系统和以NF-κB为中心的Rel/NF-κB/IKK信号系统的关键调控点,在细胞黏附、增殖和凋亡中起重要作用,与肿瘤的形成发展有着十分密切的关系,成为近几年研究的一个热点.目前对其在大肠癌组织中的表达及大肠癌细胞分化、侵袭、转移等研究尚不多见.本研究探讨了β-Cat、NF-κB的表达与大肠癌细胞生物学行为的关系.     

核转录因子κB在门静脉高压大鼠肺血管中的表达及意义

目的:探讨核转录因子-κB(NF-κB)在门脉高压大鼠肺血管中的表达及意义。方法:建立门脉高压大鼠模型,将实验动物随机分为三组:实验模型组,银杏治疗组,对照组,动态观察其肺血管NF-κBp65的表达。结果:对照组平均光密度值0.2229±0.0008、实验组0.3007±0.0044、治疗组0.2866±0.0037。造模后第2周、3周、4周,实验组为:0.2739±0.0383、0.2982±0.0754、0.3202±0.0592;治疗组为:0.2625±0.0534、0.2890±0.0686、0.2918±0.0683。对三组结果进行两两非配对t检验,都具有显著性差异(P<0.01);相同时间段实验组与治疗组间亦具有显著性差异(P<0.01)。结论:门脉高压可促成肺血管组织NF-κBp65的高表达,并在门脉高压引起的血管病变中发挥重要作用;银杏注射液对NF-κBp65的高表达有抑制作用。     

核转录因子NF-κB的研究进展

核转录因子ＮＦ κＢ(ｎｕｃｌｅａｒｔｒａｎｓｃｒｉｐｔｉｏｎｆａｃｔｏｒ κＢ ,ＮＦ κＢ)是一类关键性的核转录因子 ,通常以同源或异源二聚体非活性形式存在于几乎所有类型细胞的胞质 ,具有十分重要的功能。它与免疫细胞的活化 ,Ｔ和Ｂ淋巴细胞的发育 ,应激性反应 ,细胞凋亡等多种细胞活动有关。许多因素可激活核转录因子ＮＦ κＢ ,使其从细胞质转位于细胞核 ,与ＮＦ κＢ反应性基因的κＢ位点结合并调控ＮＦ κＢ反应性基因的转录。我们对近年来有关核转录因子ＮＦ κＢ活化的信号转导机制 ,ＮＦ κＢ对炎性分子转录的调控 ,ＮＦ …     

红霉素对支气管上皮细胞转录因子c-Jun和核因子-κB表达的影响

探讨红霉素对4-羟基壬烯醛(4-HNE)引起的支气管上皮细胞(16-HBE)核转录因子c-Jun及NF-κB的影响。将人支气管上皮细胞分为4-HNE组(10μmol/L 4-HNE)红霉素+4-HNE组、对照组,在4-HNE刺激细胞2、4、8及12h后,检测c-Jun及NF-κB的变化。结果表明,4-HNE和对照组比较,c-Jun、NF-κB自2h后各时间段两组差异有统计学意义,P均<0.05。红霉素+4-HNE组在4-HNE刺激2h后,c-Jun及NF-κB的表达较4-HNE组,差异有统计学意义,P均<0.01。4-HNE促进支气管上皮细胞c-Jun及NF-κB的表达。红霉素可抑制4-HNE诱导的c-Jun及NF-κB的表达。     

蛙皮素及其受体和核因子-κB与肿瘤的关系

肿瘤的发生发展与多种内外因素有关。目前已发现，凋亡抑制和增殖能力增强是肿瘤发生的机制之一。蛙皮素及其受体和NF-κB共同的促增殖抗凋亡的特点，使其成为肿瘤研究中的热点。     

核转录因子-κB在糖尿病大鼠正中隆起室管膜细胞的表达

目的:观察核转录因子κB(NF-κB)在糖尿病大鼠不同时期正中隆起室管膜细胞的表达差异.方法:免疫组织化学观察NF-κB在2、4、8、11周的糖尿病大鼠及正常大鼠正中隆起处细胞内的表达情况.结果:NF-κB在2周组阳性表达水平最高,与正常对照组、4周、8周、11周比较差异有统计学意义;4周、8周组表达水平下降,但与11周、正常对照组比较差异有统计学意义;11周与正常组织之间无差异.结论:糖尿病时正中隆起处NF-κB阳性表达不同时期有差异,提示正中隆起作为敏感部位在糖尿病早期时,该处的NF-κB就被激活,参与了神经内分泌及神经免疫调节.     

Identification of endotoxin-positive cells in the rat lung during shock

Summary Following an intravenous administration into rats of a shock-inducing dose of endotoxin (2 mg) the lipopolysaccharide (LPS) was demonstrated immunohistochemically (light and electron microscopy) and determined quantitatively (radio-labelled LPS) in the lung tissue and in isolated alveolar macrophages. At different times after LPS injection morphological investigations of the pulmonary tissue and alveolar macrophages were carried out.One hour after endotoxin treatment 3% of the alveolar macrophages were already LPS-positive. The maximum extent of the immunoperoxidase reaction for endotoxin (100% cells involved) was observed on day 3, the vast majority (98%) of the alveolar macrophages being LPS-positive still on day 14. 0.9% of the injected radio-labelled LPS preparation was found to be associated with lung tissue on day 3. By this time 0.173 µg LPS/10⁶ alveolar macrophages was detected. During the time of ultrastructural investigation endotoxin appeared in the lung only within cells. By their high capacity for storing endotoxin and their numerical superiority the mononuclear phagocytes are the leading LPS-positive cells in the lung, although granulocytes, endothelial cells, and alveolar epithelial cells were sometimes also involved.The accumulation of a high percentage of activated macrophages in the lung seen in the late stage of shock could represent at least one of the main factors leading to damage of pulmonary tissue. The correlation between appearance of LPS-positive macrophages and histological signs of lung tissue injury in the present investigation is striking.     

The immunocytochemical localization of tumour necrosis factor and leukotriene in the rat heart and lung during endotoxin shock

After the intravenous administration of lipopolysaccharide at a dose of 3.0 mg/100 g to rats, immunoreactive sites for tumour necrosis factor (TNF) and peptide leukotrienes (LTs) were examined in the heart and lung. Immunoreaction for TNF is preferentially localized on the apical endothelial cell surface of the vessels and in lysosomes of inflammatory and interstitial cells. Lysosomes of cardiac muscle cells which undergo degeneration are also reactive. Peptide LTs in inflammatory cells give almost the same reactions as those for TNF. However, the production of peptide LTs occurs uniquely in cardiac muscle cells in the media of the pulmonary vein, although lysosomes of intracardiac muscle cells which undergo degeneration do not show immunoreactivity. These results suggest that the degeneration of cardiac muscle cells may be induced not only by endogenous TNF but also by peptide LTs which are produced in muscle cells of the venous media and are transported to the myocardium via the coronary circulation.     

HSP70在慢性乙型肝炎患者肝组织中的表达及意义

目的探讨热休克蛋白 70 ( HSP70 )在慢性乙型肝炎肝组织中的表达及意义。方法采用免疫组化技术对 3 6例慢性乙型肝炎和 2 0例正常肝组织中 HSP70的表达进行检测。结果慢性乙型肝炎和正常肝组织中肝细胞 HSP70表达阳性率分别为 4 5 %和 15 % ,两者相比差异显著 ( χ2 =6.3 ,P<0 .0 5 ) ;中度和重度肝炎 HSP70阳性率明显高于轻度肝炎 (阳性率分别为 62 .5 %和 3 0 % ,χ2 =3 .9,P<0 .0 5 ) ;HSP70阳性细胞多位于灶性和碎屑样坏死区。结论肝细胞 HSP70的异常表达在慢性乙型肝炎免疫保护中起重要作用 ,可作为肝组织损伤的一种标志。     

Superantigen and endotoxin synergize in the induction of lethal shock

Endotoxin (lipopolysaccharide; LPS) and superantigens (exotoxins) have been identified as potent inducers of lethal shock. While endotoxin primarily interacts with CD 14 receptors on macrophages, superantigens like the staphylococcal enterotoxin B (SEB) preferentially activate T cells. Both cell types are triggered to release pro-inflammatory cytokines that in turn induce lethal shock. We analyzed whether endotoxin and superantigen interact during the induction phase of lethal shock. We report that LPS and SEB operate synergistically. Lethal doses of both inducers were reduced 100-fold when given in combination. The induced serum levels of tumor necrosis factor, interleukin-6, and interferon-γ (IFN-γ) were elevated and remained high for a prolonged period. Moreover, synergistic action of LPS and SEB induced lethal toxic shock even without presensitization of mice with D -galactosamine (D -GalN). Opposed to D -GalN-pretreated mice, mice injected with LPS and SEB showed less liver damage, but rather apoptosis of epithelial cells in the bowel. Cyclosporin A and treatment with anti-IFN-γ monoclonal antibody blocked the synergistic action of LPS and SEB, indicating that T cell-derived IFN-γ is the mediator of the observed synergism. Concomitant injection of LPS and SEB had no influence on SEB-induced T cell deletion and anergy induction. Since Gram-positive and Gram-negative bacteria can be recovered from septic blood samples, the synergistic action of endotoxin and superantigens might be relevant during lethal septicemia.     

内毒素的肺内清除与灭活

本文通过检测正常家兔入、出肺血内毒素含量。家兔肺清除~(51)Cr标记内毒素及观察大鼠先后经过肺注入内毒素的死亡率研究了肺对内毒素的清除与灭活作用。结果表明:正常家兔入肺血内毒素含量明显高于出肺血(P<0.01)。300μg~(51)Cr标记大肠杆菌内毒素一次流经肺循环的肺内清除率为50.31%。静脉注入内毒素组大鼠12及24小时死亡率明显低于动脉注入组(P<0.01和P<0.05)。上述实验结果提示肺可清除循环血中内毒素,内毒素能在肺内灭活。     

The zinc finger protein Gfi1 acts upstream of TNF to attenuate endotoxin-mediated inflammatory responses in the lung

Gfi1 is a 55-kD nuclear zinc finger protein that is differentially expressed in lymphoid and myeloid cells. Gfi1(-/-) mice show a very strong systemic response to the endotoxin LPS and die rapidly within 36 h with symptoms of septic shock. Here we report that the pathohysiological processes for this exaggerated inflammatory response take place in the lung. After LPS treatment, lungs of Gfi1(-/-) mice showed a rapid accumulation of mononuclear cells and a significant overproduction of inflammatory cytokines such as TNF, IL-1beta and IL-6. Increased cytokine production was also observed in blood-free perfused lungs from Gfi1(-/-) mice exposed to either LPS or overventilation. Alveolar macrophages but not airway epithelial cells from Gfi1(-/-) mice were found to be responsible for the enhanced cytokine production. Strikingly, when the TNF gene was deleted, Gfi1(-/-) animals were completely rescued from LPS hypersensitivity and had significantly lower IL-1beta and IL-6 levels. We conclude that the unrestrained endotoxin response of Gfi1(-/-) mice occurs mainly in the lung and that Gfi1 represents a novel factor limiting the inflammatory immune response of this organ, and propose that Gfi1 exerts its regulatory function in alveolar macrophages downstream of the LPS receptor (TLR4) and upstream of TNF.     

睡眠剥夺对HSP70表达及脑超微结构的影响

目的：观察睡眠剥夺（SD）后大鼠脑组织HSP70表达的变化及对超微结构的影响。方法：44只雄性SD大鼠随机分为11组，每组4只，免疫组织化学方法检测HSP70的表达，电镜观察海马超微结构的变化。结果：睡眠剥夺后12小时即可在大脑皮质及海马观察到HSP70阳性细胞，2—3天数量达到高峰，7天时明显下降。白天睡眠剥夺12小时（SDd12h）组HSP70阳性细胞数较夜晚睡眠剥夺12小时（SDn12h）组多（P〈0．05）。RS组大脑皮质HSP70阳性细胞数较白天睡眠剥夺1天（SDd1d）组减少（P〈0．05）。白天睡眠剥夺3天（SDd3d）海马出现超微结构改变，白天睡眠剥夺7天（SDd7d）后改变更加明显。结论：睡眠剥夺可影响大鼠脑组织HSP70表达及超微结构。     

结核杆菌热休克蛋白70基因的克隆与原核表达

目的：克隆结核杆菌热休克蛋白70(TBhsp70)基因，并在大肠杆菌中表达。方法：利用PCR技术从结核杆菌H37Rv中扩增Hsp70基因，并将其克隆到pUC19中，进行测序。将得到的Hsp70基因克隆到表达载体pGEX-4T-1中，构建重组表达质粒pGEX—TBhsp70，在大肠杆菌DH5α中进行表达。结果：成功地克隆了TBhsp70基因。DNA测序证实，与GenBank公布的序列一致。含pGEX-TBhsp70基因表达质粒的大肠杆菌经IPTG诱导后，能够表达相对分子质量(MR)约为96000的融合蛋白。结论：获得了TBhsp70基因，成功地构建了原核表达质粒pGEX-TBhsp70，并在大肠杆菌得到表达，为其相关研究奠定了一定的基础。     

miRNA-146a与肺部疾病的研究进展

MicroRNA（miRNA）是近二十年来分子生物学和遗传学领域的研究热点,随着人们对miRNA的不断研究和认识,发现miRNAs与吸入性肺损伤的发生发展密切相关。miRNA-146a是第一个被发现在免疫系统中具有调节作用的miRNA,是近年来研究较前沿、较广泛的miRNA之一,其下游基因介导参与了炎症、免疫、肿瘤的发生和发展。近年来,对miRNA-146a这种急性时相反应的负调节剂的研究越来越多,被认为是固有免疫及适应性免疫细胞分化及功能的重要调控者。本文首先从miRNA-146a在固有免疫、适应性免疫参与炎症负反馈机制出发,归纳了在Nuclear factorκB（NF-κB）信号通路中路径图,再通过回顾miRNA-146a在肺部疾病中的表达水平,对参与吸入性肺损伤及肺癌病程中分子机制及预后中作用的最新研究进展作一综述。