大鼠失血性休克并全身炎症反应综合征模型制备

目的:建立符合临床特征的、稳定的"两次打击"大鼠全身炎症反应综合征(SIRS)模型.方法:实验组取30只大鼠,股动脉放血诱发休克,随后回输全部血液.血压平稳后,在腹腔注射不同剂量的内毒素(LPS,各6只),观察各组动物的情况.实验组分为模型组和正常对照组(各6只).进行上述相应时间点血浆炎性递质各个器官功能检测,并行病理学检查.结果:模型组动物在内毒素注入后出现全身炎症反应综合征,体温下降,呼吸加快,白细胞计数和Pa o2均有不同程度降低(P＜0.05);心、肝、肾功能指标明显增高(P＜0.05),血清TNF-α含量明显升高(P＜0.05),各器官功能指标均出现不同程度的升高,明显的低血氧症和高碳酸血症.病理学观察显示肺、肝、小肠等出现不同程度的实质性损伤.结论:该实验较好的重现了失血性休克合并内毒素血症致SIRS的诱因和临床特点,为临床实验研究提供了一种可行性的SIRS动物模型,该模型为目前较理想的研究SIRS的动物模型,对SIRS发病机制的研究具有重要意义.     

肝肾综合征患者血浆TNF-α、NO及内毒素水平变化

目的:探讨肝硬化合并肝肾综合征(HRS)患者血浆一氧化氮(NO)、肿瘤坏死因子-α(TNF-α)及内毒素的改变.方法:本研究共分3组,即肝硬化合并HRS组33例;肝硬化无HRS组29例;正常对照组30例.应用ELISA双抗体夹心法测定血浆TNF-α,亚硝酸盐还原酶法测定血浆NO,采用鲎试验检测血浆内毒素,并分析血浆内毒素与一氧化氮、肿瘤坏死因子-α的相关性.结果:肝硬化合并HRS组与正常对照组比较血浆NO、TNF-α、内毒素水平差异有非常显著性意义(P＜0.01),与肝硬化无合并HRS组比较差异有显著性意义(P＜0.05),肝硬化无合并HRS组与正常对照组比较差异有非常显著性意义(P＜0.01).肝硬化合并HRS患者血浆内毒素与NO、TNF-α存在正相关,相关系数分别为0.84和0.88,P值均＜0.001.结论:肝肾综合征(HRS)患者体内血浆内毒素、NO、TNF-α均明显升高,并可能参与了肝肾综合征(HRS)产生的重要病理生理改变.     

SIRT1与乙酰化底物、NAD+或烟酰胺的相互作用

沉默信息调节因子2相关酶1 (SIRT1)是一类腺嘌呤二核苷酸(NAD+)依赖性去乙酰化酶.烟酰胺是SIRT1催化的去乙酰化反应的产物,也是SIRT1的一种非竞争性抑制剂.利用蛋白同源模建和分子对接方法构建了“SIRT1/NAD+/p53乙酰化多肽”和“SIRT1/ADPR(二磷酸腺苷核糖)/烟酰胺”的两种复合物结构模型.根据“SIRT1/NAD+/p53乙酰化多肽”的复合物模型,发现SIRT1的265位丝氨酸(S265)和346位天冬酰胺(N346)与NAD+有相互作用,275位丝氨酸(S275)位于NAD+结合口袋的入口处.通过酶动力学实验证明:将S265、N346和S275突变之后会降低甚至消除NAD+与SIRT1的相互作用.另外,根据“SIRT1/ADPR/烟酰胺”的复合物模型,烟酰胺的酰胺基团与347位异亮氨酸(I347)、348位天冬氨酸(D348)形成了氢键,同时其嘧啶环埋在由262位丙氨酸(A262)、270位异亮氨酸(I270)、273位苯丙氨酸(F273)、316位异亮氨酸(I316)和347位异亮氨酸(I347)所包围的疏水环境中.将I316突变成丙氨酸,提高了酶与烟酰胺的结合能力,也显著提高了烟酰胺的抑制活性,这一现象表明烟酰胺结合在SIRT1的C口袋处.     

Interleukin-1 receptor antagonist reduces mortality from endotoxin shock

About five out of 1,000 patients admitted to hospital develop bacterial sepsis leading to shock, the mortality rate for which is high despite antibiotic therapy. The infection results in hypotension and poor tissue perfusion, and eventually leads to the failure of several organ systems. Bacterial endotoxin is thought to be the direct cause of shock in Gram-negative sepsis, because it can cause shock in animals, and antibodies against endotoxin prevent Gram-negative shock in animals and in humans. But, the symptoms of septic shock are the result of the actions of host cytokines induced by the endotoxin. The cytokine interleukin-1 has been implicated as an important mediator of septic shock because it can induce tachycardia and hypotension and act synergistically with tumour necrosis factor to cause tissue damage and death. We now report that a specific interleukin-1 receptor antagonist reduces the lethality of endotoxin-induced shock in rabbits, indicating that interleukin-1 does indeed play an important part in endotoxin shock.     

上染过程中纤维与染料、助剂及介质的相关性

论述了上染体系中纤维与染料、纤维与助剂、纤维与介质的染色相关性。为选择适当的染料、助剂及介质去染色纤维 ,以期达到最佳的匹配提供了参考依据     

Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin

Vertebrates achieve internal homeostasis during infection or injury by balancing the activities of proinflammatory and anti-inflammatory pathways. Endotoxin (lipopolysaccharide), produced by all gram-negative bacteria, activates macrophages to release cytokines that are potentially lethal. The central nervous system regulates systemic inflammatory responses to endotoxin through humoral mechanisms. Activation of afferent vagus nerve fibres by endotoxin or cytokines stimulates hypothalamic-pituitary-adrenal anti-inflammatory responses. However, comparatively little is known about the role of efferent vagus nerve signalling in modulating inflammation. Here, we describe a previously unrecognized, parasympathetic anti-inflammatory pathway by which the brain modulates systemic inflammatory responses to endotoxin. Acetylcholine, the principle vagal neurotransmitter, significantly attenuated the release of cytokines (tumour necrosis factor (TNF), interleukin (IL)-1beta, IL-6 and IL-18), but not the anti-inflammatory cytokine IL-10, in lipopolysaccharide-stimulated human macrophage cultures. Direct electrical stimulation of the peripheral vagus nerve in vivo during lethal endotoxaemia in rats inhibited TNF synthesis in liver, attenuated peak serum TNF amounts, and prevented the development of shock.     

Recognition and plasma clearance of endotoxin by scavenger receptors.

Lipid A is the active moiety of lipopolysaccharide (LPS, also referred to as endotoxin), a surface component of Gram-negative bacteria that stimulates macrophage activation and causes endotoxic shock. Macrophages can bind, internalize and partially degrade LPS, lipid A and its bioactive precursor, lipid IVA. We report here that lipid IVA binding and subsequent metabolism to a less active form by macrophage-like RAW 264.7 cells is mediated by the macrophage scavenger receptor. Scavenger-receptor ligands inhibit lipid IVA binding to, and metabolism by, RAW cells, and lipid IVA binds to type I and type II bovine scavenger receptors on transfected Chinese hamster ovary cells. Although in vitro competition studies with RAW cells indicate that scavenger receptor binding is not involved in LPS or lipid IVA-induced stimulation of macrophages, in vivo studies show that scavenger-receptor ligands greatly inhibit hepatic uptake of lipid IVA in mice. Thus, scavenger receptors expressed on macrophages may have an important role in the clearance and detoxification of endotoxin in animals.     

含Zn,Ag或Sc的Al-Li-Cu-Mg-Zr合金正电子寿命谱研究

在深低温到室温的不同温度下，测量了不同时效状态的Ａｌ－Ｌｉ－Ｃｕ－Ｍｇ－Ｚｒ合金和含Ｚｎ，Ａｇ或Ｓｃ的Ａｌ－Ｌｉ－Ｃｕ－Ｍｇ－Ｚｒ合金的正电子寿命谱，对ｅ＾＋寿命谱特征参数的分析表明，峰值时的使热空位大量回复，缺陷的数目减少，在深低温下，空位主要以单空位形式存在且随温度升高而激活运动复合成多空位，Ｚｎ或Ａｇ的加入对空间的运动复合有束缚作用，而Ｓｃ却有助于空位的运动复合，所有实验样品低温下基体电子密