HMGB1在心血管疾病中的研究进展

高迁移率族蛋白B1(high mobility group protein box 1 protein,HMGBl)是一组高度保守的非组织核蛋白,存在于多种真核细胞的细胞核中.其可通过活化细胞的主动分泌和坏死细胞的被动释放进入胞外,并与配体结合引发信号转导,诱导炎症介质的产生,扩大炎症反应.大量研究表明,HMGB1在心血管疾病的发生发展及转归中起着重要作用,并受到人们越来越多的关注.     

早期目标血糖管理下严重脓毒症患者HMGB1的变化及其临床意义

探讨早期目标血糖管理对严重脓毒症患者HMGB1变化的影响.严重脓毒症患者随机分为血糖控制A（4.4mmol/L~6.1mmol/L）、B（6.2mmol/L~8.3mmol/L）、C（8.4mmol/L~10.0mmol/L）三组.给予早期目标血糖管理,入ICU后0d、1d、3d、5d、7d采血测TNF-α、HMGB1浓度.三组TNF-α、HMGB1浓度及APACHEⅡ评分均呈下降趋势,A组HMGB1浓度及APACHEⅡ评分在第7d较B、C组明显降低（P＜0.05）.A组28d病死率较B、C组降低（P＆gt;0.05）.严重脓毒症患者在早期目标血糖管理下,显著降低HMGB1浓度,降低病死率和改善预后,HMGB1可用来评价脓毒症的严重程度及预后.     

趋化因子10与临床疾病关系的研究进展

趋化因子10(CXCL10)是由干扰素诱导产生,过去又把它称为干扰素-γ诱导蛋白10(IFN-γInducible protein 10).其具有强大的招募中性粒细胞、促进多种细胞因子分泌及抑制部分肿瘤生长等多种生物学作用.在慢性炎症、过敏性炎症、自身免疫性疾病、移植物排斥反应和肿瘤等多种疾病的病理过程中起重要作用.     

趋化因子10与临床疾病关系的研究进展

趋化因子10（CXCL10）是由干扰素诱导产生,过去又把它称为干扰素-γ诱导蛋白10（IFN—γIndueible protein 10）。其具有强大的招募中性粒细胞、促进多种细胞因子分泌及抑制部分肿瘤生长等多种生物学作用。在慢性炎症、过敏性炎症、自身免疫性疾病、移植物排斥反应和肿瘤等多种疾病的病理过程中起重要作用。     

细胞间粘附分子在恶性血液病中的研究进展

细胞间粘附分子（inter-cellular adhesion molecules,Ⅰ-CAMs）属于免疫球蛋白超家族粘附分子,涉及细胞-细胞粘附。它在维护正常组织的稳定、介导炎症细胞的迁移及肿瘤转移等过程中起重要的作用。目前许多研究发现在白血病、淋巴瘤、骨髓瘤等恶性血液病患者中Ⅰ-CAMs高水平表达,并在血液循环中发现其可溶性分子。它们可能在恶性血液病的发生、转移、评估预后中发挥着重要的作用。     

TREM-1与肿瘤关系的研究进展

有关炎症与肿瘤相互关系的研究已成为目前肿瘤研究的热点之一.髓样细胞表达触发受体-1(TREM-1)作为一种免疫球蛋白超家族激活型受体,在炎症反应发生、级联放大中具有重要作用,可影响肿瘤微环境中各种相关细胞因子(如IL-8、MCP-1、TNF-α)水平,通过损伤、抑制修复等机制参与肿瘤发生、浸润和转移等病理性过程,影响患者预后.本文主要就TREM-1在肿瘤方面的相关研究进展进行综述.     

认识癌症与炎症间的因果关系及其意义

炎症是指机体对组织细胞损伤的反应,而癌症是指所有恶性肿瘤的总称.表面上看,两者是截然不同的.近年研究表明,大约1/5的癌症患者有长期慢性炎症刺激,因而提出＂癌症相关性炎＂的概念.显然,炎症是因,癌症是果.但是,4/5的癌症患者并找不到慢性炎症背景,然而,其癌症组织内也有炎细胞浸润,此种情况癌症应为因,但机理基本上不清楚.癌症与炎症的因果关系主要包括上述两种情况,阐明其机理对患者的防治均有重要意义.     

白介素-1家族在动脉粥样硬化中的作用

动脉粥样硬化(AS)是一种慢性炎症性疾病。促炎细胞、促炎因子以及抗炎细胞、抗炎因子在此过程中发挥了重要作用,双方相互抑制,特定环境可相互促进,构成了一个复杂的炎症网络系统。平衡打破则表现为促炎活性升高和抑炎活性降低,可促进斑块的进展和不稳定,导致心血管事件。近年来白细胞介素(IL)-1家族在AS过程中的作用受到重视。依据其在AS进程中的作用,将其分为促AS家族,抗AS家族以及未归类成员。     

骨桥蛋白在心肌梗死后心力衰竭中研究进展

骨桥蛋白是一种糖基化的多功能蛋白,其具有激活细胞内信号传导、参与炎症细胞的趋化聚集、促进肿瘤的生长迁移等多种生物学功能。近年来研究表明其在心肌梗死后的炎症反应、心室重塑、细胞外基质沉积及肾素-血管紧张素-醛固酮系统的过度激活中具有重要的作用,同时其与心肌梗死后心力衰竭的严重程度及顸后亦密切相关。本文就骨桥蛋白在心肌梗死后心力衰竭中研究进展做一综述。     

帕金森病发病与小胶质细胞老化关系的探讨

帕金森病(PD)是一种中老年常见的神经退行性病变.其发病机制可能与小胶质细胞(MI)的慢性炎症反应有关.老化的M1通过释放炎症介质导致多巴胺(DA)神经元大量死亡,帕金森病临床发病.因此澄清MI老化的原因对于了解PD发病及防治策略具有重要意义.     

严重脓毒症与免疫功能障碍

脓毒症多呈现典型的促炎效应和抗炎反应,并与获得性免疫功能障碍同时出现,且免疫细胞中超过80％的基因表达发生改变。由于单核／巨噬细胞细胞因子谱的改变、主要组织相容性复合体Ⅱ类抗原（MHCⅡ）及共刺激分子表达下降以及树突状细胞的凋亡,诱发细胞免疫功能下降;中性粒细胞活性降低和补体系统的激活,又增加感染易感性。T淋巴细胞表现...     

Models of white matter injury: comparison of infectious, hypoxic-ischemic, and excitotoxic insults

White matter damage (WMD) in preterm neonates is strongly associated with adverse outcome. The etiology of white matter injury is not known but clinical data suggest that ischemia-reperfusion and/or infection-inflammation are important factors. Furthermore, antenatal infection seems to be an important risk factor for brain injury in term infants. In order to explore the pathophysiological mechanisms of WMD and to better understand how infectious agents may affect the vulnerability of the immature brain to injury, numerous novel animal models have been developed over the past decade. WMD can be induced by antenatal or postnatal administration of microbes (E. coli or Gardnerella vaginalis), virus (border disease virus) or bacterial products (lipopolysaccharide, LPS). Alternatively, various hypoperfusion paradigms or administration of excitatory amino acid receptor agonists (excitotoxicity models) can be used. Irrespective of which insult is utilized, the maturational age of the CNS and choice of species seem critical. Generally, lesions with similarity to human WMD, with respect to distribution and morphological characteristics, are easier to induce in gyrencephalic species (rabbits, dogs, cats and sheep) than in rodents. Recently, however, models have been developed in rats (PND 1-7), using either bilateral carotid occlusion or combined hypoxia-ischemia, that produce predominantly white matter lesions. LPS is the infectious agent most often used to produce WMD in immature dogs, cats, or fetal sheep. The mechanism whereby LPS induces brain injury is not completely understood but involves activation of toll-like receptor 4 on immune cells with initiation of a generalized inflammatory response resulting in systemic hypoglycemia, perturbation of coagulation, cerebral hypoperfusion, and activation of inflammatory cells in the CNS. LPS and umbilical cord occlusion both produce WMD with quite similar distribution in 65% gestational sheep. The morphological appearance is different, however, with a more pronounced infiltration of inflammatory cells into the brain and focal microglia/macrophage ("inflammatory WMD") in response to LPS compared to hypoperfusion evoking a more diffuse microglial response usually devoid of cellular infiltrates ("ischemic WMD"). Furthermore, low doses of LPS that by themselves have no adverse effects in 7-day-old rats (maturation corresponding to the near term human fetus), dramatically increase brain injury to a subsequent hypoxic-ischemic challenge, implicating that bacterial products can sensitize the immature CNS. Contrary to this finding, other bacterial agents like lipoteichoic acid were recently shown to induce tolerance of the immature brain suggesting that the innate immune system may respond differently to various ligands, which needs to be further explored.     

Chronic psychosocial stress increases the risk for inflammation-related colon carcinogenesis in male mice

Patients with inflammatory bowel diseases (IBDs) have a higher risk of developing colorectal cancer (CRC) than the general population. Furthermore, chronic psychosocial stress increases the likelihood of developing IBD and multiple types of malignant neoplasms, including CRC. Here, for the first time, we investigate the effects of chronic psychosocial stress in male mice on an artificially induced CRC, by employing the chronic subordinate colony (CSC) housing paradigm in combination with the reliable azoxymethane (AOM)/dextran sodium sulfate (DSS) CRC model. Colonoscopy revealed that CSC mice showed accelerated macroscopic suspect lesions. In addition, more CSC mice developed low-grade dysplasia (LGD) and/or high-grade dysplasia (HGD) in the colonic tissue compared to the single-housed control mice (SHC). CSC mice showed an increased number of Ki67+ and a decreased number of terminal deoxynucleotidyl transferase dUTP nick end labeling epithelial cells in colonic tissue. Colonic liver receptor homolog-1 (LRH-1), cyclooxygenase II (COXII), tumor necrosis factor, forkhead box P3 (FoxP3) mRNA as well as colonic ?-catenin, COXII, and LRH-1 protein expression were also increased in CSC compared with SHC mice. Although the number of CD4+ Th cells was increased, a tendency toward a decreased colonic interferon-γ (IFN-γ) mRNA expression was observed. Furthermore, despite an increased percentage of CD3+ cells and CD3+/FoxP3+ double-positive cells within mesenteric lymph node cells of CSC mice, IFN-γ secretion from these cells was unaffected. Altogether, our results suggest that chronic psychosocial stress increases the risk for AOM/DSS-induced and, thus, inflammation-related CRC. Finally, assessment of additional time points may test whether the shift from tumor-protective Th1 cell to regulatory T-cell immunity represents a consequence of increased carcinogenesis or a causal factor involved in its development.     

Cytokine production by spleen cells after social defeat in mice: activation of T cells and reduced inhibition by glucocorticoids

Social disruption (SDR) is an effective model of social stress associated with an enhanced inflammatory reactivity of the immune system. The aim of the present study was to further describe SDR effects on cytokine production by spleen cells, testing selectively monocyte and T cell functions as a result of this stressor. For this purpose, splenocytes from control mice (C) and mice socially stressed for 7 days (SDR) were cultured in the presence of lipopolysaccharide (LPS) or concanavalin A (Con A). Splenocyte proliferation, cytokine production and sensitivity of spleen cells to corticosterone were assessed in vitro. The humoral response to keyhole limpet hemocyanin (KLH) immunization was assessed. SDR induced splenomegaly and enhanced splenocyte basal proliferation. The pro-inflammatory influence of SDR was confirmed by an increased release of interleukin-6 (IL-6) by LPS-stimulated cultures and by a reduced sensitivity of spleen cells to the anti-inflammatory effect of corticosterone. The mechanism increasing cytokine production in response to LPS was cytokine specific, since among inflammatory cytokines, IL-6 but not interferon-gamma (IFN-gamma) was enhanced by stress. In stressed mice, the increase in IL-6 and IFN-gamma and the decrease in IL-10 release in Con A-stimulated cultures indicate that SDR did not modify the Th1/Th2 cytokine balance but globally activated T cells. Plasma anti-KLH antibody levels were similar in both groups. Wounded and non-wounded mice presented similar responses to stress. This study shows that social disruption stress enhances the reactivity of cells from both the acquired and innate immune systems.     

替格瑞洛与氯吡格雷对急性STEMI患者急诊PCI术后炎症因子的影响

为比较替格瑞洛与氯吡格雷对急性ST段抬高型心肌梗死（STEMI）患者急诊经皮冠状动脉介入术（PCI）术后炎症因子的影响,将176例急性STEMI且行急诊PCI术的患者分为替格瑞洛组（A组）58例、氯吡格雷常规组（B组）58例、氯吡格雷强化组（C组）60例,分别测定术前、术后12小时、术后7天、术后1个月、术后3个月、6个月时炎症因子e反应蛋白（CRP）、白细胞介素-6（IL6）、髓过氧物酶（MPO）、可溶性CD40受体（sCD40L）的含量,比较3组患者各炎症因子在不同时间点有无统计学差异。结果显示c组和A组较B组明显降低（P〈0．05）,有统计学意义,而A组较c组稍降低（P〉0．05）,但两者无统计学意义。由此可见,替格瑞洛的抗炎作用较常规剂量氯吡格雷作用明显增强,和强化剂量氯吡格雷作用相仿。     

Cytodiagnosis in the cerebrospinal fluid with special reference to illness course phases in diseases of the central nervous system

The cytological diagnostic of CSF is indicated in inflammations, vascular and tumorous diseases. A change of normal ratio of 4:1 of CSF-lymphocytes and -monocytes and/or the appearance of functionally active forms of these cell-lines are typical for immunoreactive inflammation (lymphoid cells) or cleaning up (macrophages). Cellular reactions with differing pleocytosis are caused by different irritations within the space of CSF: during the acute phase of meningitis with granulocytosis, in the following cleaning up with monocytosis and macrophages and in inflammatory and immunological reactions with lymphocytosis, lymphoid cells and plasmocytes. Necessary to CSF-diagnostic is the correlation of the stages of the course of disease additional with regard to the quantitative and qualitative results of CSF-protein. Findings of the examination of CSF-cells in diseases of CNS are represented in tabular form.     

Stress-induced facilitation of host response to bacterial challenge in F344 rats is dependent on extracellular heat shock protein 72 and independent of alpha beta T cells

Activation of the in vivo stress response can facilitate antibacterial host defenses. One possible mechanism for this effect is stress-induced release of heat shock protein 72 (Hsp72) into the extracellular environment. Hsp72 is a ubiquitous cellular protein that is up-regulated in response to cellular stress, and modulates various aspects of immune function including macrophage inflammatory/bactericidal responses and T-cell function when found in the extracellular environment. The current study tested the hypothesis that in vivo extracellular Hsp72 (eHsp72) at the site of inflammation contributes to stress-induced restricted development of bacteria, and facilitated recovery from bacteria-induced inflammation, and that this effect is independent of alpha beta (αβ) T cells. Male F344 rats were exposed to either inescapable electrical tail-shocks or no stress, and subcutaneously injected with Escherichia coli (ATCC 15746). The role of eHsp72 was investigated by Hsp72-immunoneutralization at the inflammatory site. The potential contribution of T cells was examined by testing male athymic (rnu/rnu) nude rats lacking mature αβ T cells and heterozygous thymic intact control (rnu/+) rats. The results were that stressor exposure increased plasma concentrations of eHsp72 and facilitated recovery from bacterial inflammation. Immunoneutralization of eHsp72 at the inflammatory site attenuated this effect. Stressor exposure impacted bacterial inflammation and eHsp72 equally in both athymic and intact control rats. These results support the hypothesis that eHsp72 at the site of inflammation, and not αβ T cells, contributes to the effect of stressor exposure on subcutaneous bacterial inflammation.     

Dietary ethyl-eicosapentaenoic acid but not soybean oil reverses central interleukin-1-induced changes in behavior, corticosterone and immune response in rats

Omega (n)-3 and n-6 fatty acids are important membrane components of neurons and immune cells, and related to psychiatric and inflammatory diseases. Increased ratio of n-6/n-3 in the blood has been reported in depressed patients and in students following stress exposure. The n-3 fatty acid, eicosapentaenoic acid (ethyl-EPA) suppresses inflammation and has antidepressant properties. Interleukin (IL)-1beta can stimulate corticosterone secretion, induce anxiety and stress-like behavior and inflammatory responses. This study was to evaluate the effect of diets enriched with coconut oil, ethyl-EPA and soybean oil on central IL-1beta induced stress and anxiety-like behavior, induced changes in the concentration of prostaglandin (PG) E2 and corticosterone and the release of IL-10. Groups of rats were fed with either 5% coconut oil (as control diet), 0.2% EPA with 4.8% coconut oil or 1% EPA with 4% coconut oil and 5% soybean oil for 7 weeks. The central administration of IL-1beta induced sickness, stress and anxiety-like behavior as indicated by a reduction in body weight, decreased time spent, and the number of entries, into the open arms of the elevated plus maze and decreased exploration and entry into the central zone of the "open field" apparatus. IL-1beta also increased PGE2 and corticosterone concentrations and decreased the release of IL-10 from leucocytes. Food enriched with ethyl-EPA but not soybean oil, significantly attenuated most of these changes. These results demonstrate that ethyl-EPA has anti-inflammatory, anti-stress and anti-anxiety effects in rats.