VEGF在脓毒症毛细血管渗漏中的作用

脓毒症发病率高、痫死率高、治疗费用高,是危重患者主要死亡原因之一,其根本发病机制不清。近年研究表明,微血管通透性增加是脓毒症发生发展的关键因素,而血管内皮生长因子（VEGF）是控制血管通透性的关键分子,是导致炎症相关毛细血管通透性增加的潜在因素。脓毒症早期VEGF增高,致微血管通透性增加,毛细血管渗漏,加重炎症反应,脓毒症患者普遍存在毛细血管渗漏现象。VEGF是一种细胞因子,广泛存在于机体并参与体内多种疾病过程。本文对VEGF在脓毒症中的作用机制加以综述。     

脓毒症的微循环障碍监测研究进展

<正>脓毒症微循环障碍是重要的病理过程之一,中心环节为炎症反应。炎症反应既可保卫机体,也可通过反馈效应及前炎症效应造成机体损害[1]。通过监测微循环的变化及早发现并及早干预脓毒症是目前临床研究的热点之一。脓毒症与微循环障碍有效循环血量明显下降及组织器官低灌注是脓毒症的血流动力学的特征,组织缺氧为脓毒症的病理生理特点。对于脓毒性休克的早期诊断与治疗,主要用血流动力学指标进行评估,包括尿量、中心静     

脓毒症与凝血功能紊乱

脓毒症凝血反应是一柄“双刃剑”。早期凝血激活有助于感染的局限,但凝血活化与炎症反应相互作用,一旦 超过机体的调控能力甚至转化为失控的弥漫性微血管内血栓形成可导致器官损害。血管内皮细胞在脓毒症时抗凝 及纤溶功能受损,而促凝反应占优势。阻断过度的凝血- 炎症反应可能对脓毒症治疗有益,血小板、中性粒细胞胞 外诱捕网、微粒体和多糖包被在脓毒症凝血- 炎症反应中的作用值得关注。脓毒症抗凝治疗是否改善预后的关键 在于选择合适的治疗对象及恰当的时机。     

脓毒症机体免疫变化及治疗的研究进展

脓毒症（Sepsis）为感染引起的全身炎症反应综合征（Systemic inflammatory Response Syndrome,sins）,是导致重症监护病房（ICU）患者死亡的主要原因之一,传统观念认为脓毒症是过度炎症反应的一系列综合征,也就是灭活病原体的机体免疫反应被过度活化,炎症反应失控,导致机体自身损伤,从而造成多器官功能障碍（MODS）和死亡。     

浅谈miRNA与脓毒症

脓毒症是指由感染引起的全身炎症反应综合征（systemicinflammatoryresponsesyndrome,SIRS）,脓毒症的发生和发展与机体的免疫功能紊乱密切相关[1]。因miRNA对机体免疫有特殊的调控作用,故在脓毒症发病机制的研究中受到越来越多的关注。     

脓毒症大鼠血清miR-155的表达及其意义

目的:探讨脓毒症大鼠血清中miR-155的表达及其意义。方法:建立盲肠结扎穿孔脓毒症大鼠模型。检测造模前、后大鼠血清中IL-6、TNF-α和CRP水平,评估脓毒症炎症反应情况;实时荧光定量RT-PCR检测大鼠血清中miR-155的表达;Pearson相关分析评估血清miR-155的表达与血IL-6、TNF-α和CRP水平之间的关系。结果:脓毒症大鼠血清miR-155水平较正常对照组和假手术组高(均P0.01),术后2 h血清miR-155表达迅速升高。Pearson相关分析显示血清miR-155的表达分别与IL-6、TNF-α和CRP呈正相关(P0.01)。结论:脓毒症大鼠血清miR-155表达显著增高,其水平反映机体炎症反应状态,可能作为反应脓毒症早期机体炎症水平的指标。     

脓毒症神经调节机制的研究进展

神经系统在机体炎症反应及脓毒症的发展中具有重要作用。脓毒症早期 ,神经系统即将炎症信息迅速传递到中枢神经 ,从而通过调节内分泌系统、免疫系统等影响脓毒症的病理过程。近年来的研究表明 ,神经系统本身也可通过神经递质直接参与调节脓毒症的发生与发展 ,这为脓毒症的防治提供了新思路。1　神经系统是脓毒症时传递信息的“高速公路”外周神经可感知局部环境因素的变化 ,并以非连续性、闪电式方式将信息传递到大脑 ,启动中枢神经的调控功能 ,引起体温、呼吸、体内激素水平、免疫细胞活化、炎症介质产生等一系列变化[1] 。这比炎症的缓慢…     

脓毒症与炎性因子的研究进展

<正>脓毒症(sepsis):指各种感染引起的全身炎症反应综合症,是感染性疾病常见的危重症,死亡率较高,脓毒症的发病是多重因素综合作用的结果,传统的观点认为脓毒症是由炎症反应过度所致。机体受到病原体感染时,病原体表面的抗原被机体炎症效应细胞表面的受体识别,并通过抗原、抗体反应及酶的活化途径,激活细胞内转录因子(如核因子NF-κB),并诱导多种促炎因子和炎性介质的生成及释放[1]。这些促炎因子和介质之间通过正反馈形式     

噬血细胞综合征与脓毒症的鉴别要点

噬血细胞综合征和脓毒症均存在过度炎症反应,临床表现部分重叠.然而针对噬血细胞综合征的积极免疫抑制治疗与脓毒症治疗原则截然不同,早期准确诊断至关重要.血细胞显著减少、脾肿大、高铁蛋白血症、低纤维蛋白原血症及高甘油三酯血症对鉴别两种疾病具有重要价值,基因检测、细胞因子谱和免疫表型可能对鉴别诊断有协助作用;发热、噬血现象、自...     

乌司他丁治疗脓毒症的研究进展

脓毒症是机体免疫系统受到强烈刺激，进而引起多种生物级联反应所致，包括炎症反应过程、凝集纤溶系统改变等。在炎性疾病状态下内源性的乌司他丁（UTI）被严重消耗，使其不足以抵抗剧烈炎症的损害，此时提供外源性的UTI对于保护机体免遭炎性介质损害十分必要。现就UTI治疗脓毒症的进展情况综述如下。     

脓毒症免疫细胞凋亡研究进展

尽管有关脓毒症基础和临床研究均取得一定进展,脓毒症发病率和死亡率依然居高不下,临床脓毒症的诊治面临极大的困难,成为威胁人类健康的主要原因之一.近十年来,大量有关脓毒症病理生理过程中细胞凋亡的研究使人们逐渐认识到,树突状细胞、巨噬细胞、T淋巴细胞等免疫效应细胞过度凋亡是导致脓毒症免疫功能紊乱的关键环节,抑制上述细胞凋亡能够显著改善机体免疫状态,提高脓毒症动物的生存率.因此,明确脓毒症状态下,免疫细胞发生凋亡的诱导因素和信号传导途径就显得尤为重要,本文就免疫细胞凋亡在脓毒症发病机制中的地位及新的干预手段进行综述.     

Toll-like receptors: new therapeutic targets for the treatment of atherosclerosis, acute coronary syndromes, and myocardial failure

The toll-like receptors (TLRs) are a class of transmembrane molecules that have important functions in both innate and acquired immunity. As part of the body's normal immune defense against microbial pathogens, stimulation of these receptors will trigger the inflammatory response cascade and the release of cytokines. Activation of these receptors also plays a role in a variety of systemic inflammatory diseases such as asthma, sepsis, atherosclerosis, acute coronary artery disease, and left ventricular remodeling. Pharmacologic approaches to modify the actions of TLRs are now under consideration as potential treatments for inflammatory systemic diseases that include atherosclerosis. At the same time, it is essential to characterize the benefits and risks of modifying such an important part of the body's innate immune system.     

Role of hematopoietic growth factors in non-neutropenic infections and sepsis

Therapy with colony-stimulating factors has been extended beyond their use in accelerating myeloid cell recovery to take advantage of their immune function-enhancing properties. Studies in animal models and with human subjects suggest a potential role as adjunctive therapy in infections of non-neutropenic hosts, including those with sepsis. Granulocyte colony-stimulating factor may play a pivotal role in the induction of lipopolysaccharide desensitization by nontoxic lipid A analogues proposed for the prevention of sepsis; granulocyte macrophage colony-stimulating factor may be useful in reversing the immune paralysis described in later stages of sepsis. Significant issues of exogenous colony-stimulating factor therapy must be addressed, however: the optimal timing, dose, and clinical context (e.g., type of immunosuppression, duration of infection-inciting stimulus) as well as tissue-specificity of the activities and net effect of potentially conflicting responses (e.g., immune restorative and procoagulant effects of granulocyte macrophage colony-stimulating factor). Resolution of these issues will require carefully designed clinical studies with meticulous monitoring of immunologic parameters.     

血必净联合乌司他丁治疗脓毒血症临床研究

目的观察血必净联合乌司他丁治疗脓毒血症临床效果。方法 218例重症肺炎患者随机分为对照组、血必净组、乌司他丁（UTI）组及血必净＋UTI联合治疗组。测定纤支镜肺灌洗液中炎症因子IL-6、肿瘤坏死因子-α（TNF-α）浓度,监测血浆降钙素原（PCT）及T淋巴细胞亚群变化,评估免疫功能变化。结果与对照组相比,联合治疗组纤支镜肺灌洗液IL-6、TNF-α及血浆PCT均明显下降（P〈0.05）,T细胞亚群水平明显提高（P〈0.05）,免疫功能改善。结论血必净联合UTI可更有效改善脓毒血症疗效,与强力抗感染、改善免疫功能有关。     

Association of mannose-binding lectin polymorphisms with sepsis and fatal outcome, in patients with systemic inflammatory response syndrome

Genetic factors may predispose critically ill patients to increased risk of developing sepsis. Mannose-binding lectin (MBL) is an important factor in innate immune defense. We investigated whether MBL gene polymorphisms causing low levels of MBL are associated with the development and progression of sepsis in adult patients in intensive care units. In 272 prospectively monitored patients with systemic inflammatory response syndrome, different MBL genotypes were compared, with respect to microbiology, sepsis development, and survival. The presence of MBL variant alleles was associated with the development of sepsis, severe sepsis, and septic shock. An increased risk of fatal outcome was observed in patients carrying variant alleles. These data show that MBL insufficiency plays an important role in the susceptibility of critically ill patients to the development and progression of sepsis and confers a substantial risk of fatal outcome.     

Aging and the dendritic cell system: implications for cancer

The immune system shows a decline in responsiveness to antigens both with aging, as well as in the presence of tumors. The malfunction of the immune system with age can be attributed to developmental and functional alterations in several cell populations. Previous studies have shown defects in humoral responses and abnormalities in T cell function in aged individuals, but have not distinguished between abnormalities in antigen presentation and intrinsic T cell or B cell defects in aged individuals. Dendritic cells (DC) play a pivotal role in regulating immune responses by presenting antigens to na?ve T lymphocytes, modulating Th1/Th2/Th3/Treg balance, producing numerous regulatory cytokines and chemokines, and modifying survival of immune effectors. DC are receiving increased attention due to their involvement in the immunobiology of tolerance and autoimmunity, as well as their potential role as biological adjuvants in tumor vaccines. Recent advances in the molecular and cell biology of different DC populations allow for addressing the issue of DC and aging both in rodents and humans. Since DC play a crucial role in initiating and regulating immune responses, it is reasonable to hypothesize that they are directly involved in altered antitumor immunity in aging. However, the results of studies focusing on DC in the elderly are conflicting. The present review summarizes the available human and experimental animal data on quantitative and qualitative alterations of DC in aging and discusses the potential role of the DC system in the increased incidence of cancer in the elderly.     

Pathogenesis, diagnosis and management of paraneoplastic glomerulonephritis

Paraneoplastic glomerulonephritis is a rare complication of malignancy that is frequently mistaken for idiopathic glomerulonephritis. Failure to recognize paraneoplastic glomerulonephritis can subject patients to ineffective and potentially harmful therapy. The pathology of paraneoplastic glomerulonephritis varies between different types of malignancies. This Review discusses the association of glomerulonephritis with both solid tumors and hematological malignancies. The pathogenetic mechanisms of many glomerular lesions seem to relate to altered immune responses in the presence of a malignancy. Studies in the Buffalo/Mna rat model of spontaneous thymoma and nephrotic syndrome indicate that polarization of the immune response toward a T-helper-2 (T(H)2) profile has an important role in the development of thymoma-associated glomerular lesions. Furthermore, overexpression of the T(H)2 cytokine interleukin 13 in rats induces minimal change disease. Such findings from experimental studies might facilitate the identification of biomarkers that can distinguish paraneoplastic glomerulonephritis from idiopathic and other secondary glomerulonephritides. This Review describes potential pathogenetic mechanisms for paraneoplastic glomerulonephritides associated with different malignancies and highlights the need for a multidisciplinary approach to the management of patients with paraneoplastic glomerulonephritis.     

Les lymphocytes TH17 : différenciation, phénotype, fonctions, et implications en pathologie et thérapeutique humaine

Differentiation of naive CD4⁺ T helper (T_H) cells is a major step of the adaptative immune response. When activated by pathogens in a specific cytokine environment, CD4⁺ T cells differentiate into different subsets of T_H cells with specific effector functions. T_H1 lymphocytes orchestrate cellular immune response by producing interferon-γ and stimulating cytotoxic cells whereas T_H2 cells orchestrate humoral immune response by producing interleukin-4 (IL-4), IL-5 and IL-10, leading to immunoglobulin production. Conversely, regulatory T cells (Treg) are capable of inhibiting immune response. Recently discovered, T_H17 cells are characterized by their ability to produce IL-17 and play an important role in anti-infectious and inflammatory immune responses. This review focuses on present knowledge about T_H17 cells: their induction, phenotype, functions, implications in host defense and human disease, and their potential to represent possible therapeutic targets.