单核细胞趋化蛋白-1与缺血性卒中

炎症反应在缺血性卒中的发生和发展过程中起着重要作用.单核细胞趋化蛋白-1(monocyte chemotactic protein-1,MCP-1)是趋化因子CC类哑家族成员之一,可趋化和激活单核细胞、T细胞等多种细胞,促进细胞因子表达,参与缺血性脑损伤的发生.文章对MCP-1与缺血性卒中相关的研究进展做了综述.     

高迁移率蛋白B1的生物学特性与肝细胞癌关系研究进展

高迁移率蛋白B1(high-mobility group box-1 protein B1,HMGB1)是细胞死亡和存活的重要调节因子。研究表明,HMGB1与多种肿瘤的诱发、生长、浸润和转移有关。肝细胞癌(hepatocellular carcinoma,HCC)是最常见的肿瘤之一,其发生、发展与炎症密切相关。近年来,HMGB1在HCC中的作用越来越受到关注。本文就HMGB1与炎症的关系及其在HCC发生、发展和治疗中作用的研究进展进行综述。     

高迁移率族蛋白B1与中枢神经系统疾病

高迁移率族蛋白Bl(high mobility group box 1,HMGB1)是高迁移率族蛋白家族成员.HMGB1可与细胞表面特定受体--晚期糖基化终产物受体(receptor for advanced glvcation end products,RAGE)和Toll样受体2(toll like receptor2,TLR2)结合,从而具有广泛的生物学活性.在中枢神经系统,HMGB1参与炎症反应、血脑屏障通透性调节等病理生理学过程,并与缺血性卒中、阿尔茨海默病以及神经胶质瘤等疾病密切相关.     

T淋巴细胞在缺血性脑损伤中的作用

缺血性脑损伤程度与卒中的病死率和致残率密切相关,如何最大程度地限制缺血性脑损伤,促进神经功能恢复,是当今神经科学领域十分关注的研究热点之一.大量研究表明,多种因素参与了缺血性脑损伤的病理过程.其中,T淋巴细胞介导的免疫炎症反应在缺血性脑损伤中的作用越来越受到关注,文章主要综述了T细胞在缺血性脑损伤中的作用.     

T淋巴细胞在缺血性脑损伤中的作用

缺血性脑损伤程度与卒中的病死率和致残率密切相关,如何最大程度地限制缺血性脑损伤,促进神经功能恢复,是当今神经科学领域十分关注的研究热点之一.大量研究表明,多种因素参与了缺血性脑损伤的病理过程.其中,T淋巴细胞介导的免疫炎症反应在缺血性脑损伤中的作用越来越受到关注,文章主要综述了T细胞在缺血性脑损伤中的作用.     

牙周病与缺血性卒中

牙周病是一种常见的感染性疾病,其致病病原体可通过多种途径诱导和加速动脉粥样硬化性病变,从而促进缺血性卒中的发生。大量流行病学证据表明牙周病,如牙周炎、牙龈炎等与缺血性卒中有关。     

胱抑素C与缺血性卒中关系的研究进展

正缺血性卒中是脑血管疾病亚型中最常见的类型。胱抑素C又名半胱氨酸蛋白酶抑制剂C,是蛋白酶抑制剂超家族成员之一,具有多种生物学作用,广泛参与机体多种生理和病理学过程。胱抑素C是反映肾功能的较敏感的内源性指标,除了可以评价肾功能,也参与了动脉粥样硬化的发生,还可能是缺血性卒中的危险因素[1-6]。笔者就胱抑素C与缺血性卒中关系的研究现状作一     

HMGB1在缺血性心衰中作用的研究进展

HMGB1是一种DNA结合蛋白,主要起维持核小体结构、调节基因转录、复制、DNA修复等作用。最近,针对HMGB1功能的研究主要着重于其对细胞的细胞外调节作用,HMGB1除在细胞核内存有活性外,它更有着细胞因子的功能。近年来在发展中国家,心血管疾病越来越被视为发病和死亡的一个重要原因,而慢性心力衰竭作为各种心脏病发展的严重阶段,正成为本世纪最重要的心血管疾病。随着流行病学的变迁和社会经济的发展,冠心病作为心衰的主要病因之一在我国显得越来越突出,越来越多的研究显示HMGB1在缺血性心衰发生及发展中起着多种重要作用。     

牙周病与缺血性卒中

牙周病是一种常见的感染性疾病,其致病病原体可通过多种途径诱导和加速动脉粥样硬化性病变,从而促进缺血性卒中的发生.大量流行病学证据表明牙周病,如牙周炎、牙龈炎等与缺血性卒中有关.     

富亮氨酸ɑ2-糖蛋白-1调节转化生长因子-β信号通路在缺血性卒中中的作用

富亮氨酸ɑ-2糖蛋白-1(leucine-richɑ2-glycoprotein-1,LRG1)作为富含亮氨酸重复序列蛋白家族成员之一,通过转化生长因子-β(transforming growth factor-β,TGF-β)信号通路影响多种疾病,与脑缺血后的血管生成、内皮细胞凋亡和自噬、炎症反应以及血脑屏障破坏关系密切,有望成为缺血性卒中的新型标志物及治疗靶点。然而,目前探讨LRG1与缺血性卒中关系的研究较少,对于其分子机制认识尚不完善,致使对LRG1在缺血性卒中中的作用存在争议。因此,文章就LRG1-TGF-β信号通路与缺血性卒中的研究进展进行综述,期望为缺血性卒中的早期诊断和防治提供新思路。     

急性脑梗死血清高迁移率族蛋白B1水平的变化及意义研究

目的通过检测急性脑梗死（acute cerebral infarction,ACI）患者血清高迁移率族蛋白B1（high mobil-ity group box 1,HMGB1）水平的变化,探讨HMGB1与ACI病情的关系。方法测定128例ACI患者、46名健康对照者血清HMGB1水平,观察比较ACI患者在不同病情、不同梗死面积时血清HMGB1水平的变化,对发病后48h病情发展变化进行评定,根据评分结果分为进展型与完全型脑梗死两组进行观察比较。结果 ACI患者血清HMGB1水平〔（9.05±2.03）μg/ml〕明显高于健康对照组〔（1.07±0.59）μg/ml〕,且HMGB1水平随神经功能缺损程度评分增高亦明显升高;进展性脑梗死患者血清HMGB1水平明显高于非进展性患者。结论 HMGB1一定程度上是预测ACI患者病情严重程度及进展的相关生化指标之一。     

High-mobility group box 1 activates integrin-dependent homing of endothelial progenitor cells

Endothelial progenitor cells (EPCs) are recruited to ischemic regions and improve neovascularization. Integrins contribute to EPC homing. High-mobility group box 1 (HMGB1) is a nuclear protein that is released extracellularly on cell necrosis and tissue damage, eliciting a proinflammatory response and stimulating tissue repair. In the present study, we investigated the effects of HMGB1 on EPC homing. EPCs express the HMGB1 receptors RAGE (receptor for advanced glycation end products) and TLR2 (Toll-like receptor 2). EPC migration was stimulated by HMGB1 in a RAGE-dependent manner. In addition, the HMGB1-induced migration of EPCs on fibronectin and fibrinogen was significantly inhibited by antibodies against beta1 and beta2 integrins, respectively. Short-term prestimulation of EPCs with HMGB1 also increased EPC adhesion to endothelial cell monolayers, and this effect was blocked by antibodies to beta2 integrins or RAGE. HMGB1 increased EPC adhesion to the immobilized integrin ligands intercellular adhesion molecule-1 and fibronectin in a RAGE-dependent manner. Strikingly, HMGB1 rapidly increased integrin affinity and induced integrin polarization. Using intravital microscopy in a tumor model of neovascularization, prestimulation of EPCs with HMGB1 enhanced the initial in vivo adhesion of EPCs to microvessels and the recruitment of EPCs in the tumor tissue. In addition, prestimulation of EPCs with HMGB1 increased the homing of EPCs to ischemic muscles. In conclusion, these data represent a link between HMGB1 and integrin functions of EPCs and demonstrate that HMGB1 stimulates EPC homing to ischemic tissues. These results may provide a platform for the development of novel therapeutic approaches to improve EPC homing.     

Astrocytic high-mobility group box 1 promotes endothelial progenitor cell-mediated neurovascular remodeling during stroke recovery

Crosstalk between the brain and systemic responses in blood is increasingly suspected of playing critical roles in stroke. However, how this communication takes place remains to be fully understood. Here, we show that reactive astrocytes can release a damage-associated molecular-pattern molecule called high-mobility-group-box-1 (HMGB1) that promotes endothelial progenitor cell (EPC)-mediated neurovascular remodeling during stroke recovery. Conditioned media from reactive astrocytes increase EPC proliferation in vitro. siRNA suppression of HMGB1 in astrocytes or blockade of the HMGB1 receptor for advanced glycation endproducts in EPCs prevents this effect. In a mouse model of focal cerebral ischemia, reactive astrocytes in the peri-infarct cortex up-regulate HMGB1 at 14 d poststroke, along with an accumulation of endogenous EPCs. In vivo siRNA suppression of HMGB1 blocks this EPC response, reduces peri-infact angiogenesis, and worsens neurological deficits. Taken together, these molecular and in vivo findings support a previously undescribed mechanism of crosstalk between reactive astrocytes and EPCs wherein HMGB1 promotes neurovascular remodeling and functional recovery after stroke and brain injury.     

急性脑梗死患者高迁移率族蛋白B1和过氧化小体增殖剂激活型受体βmRNA的表达

目的研究急性脑梗死患者血清高迁移率族蛋白B1（HMGBI）与外周血淋巴细胞过氧化小体增殖刹激活型受体γ（PPARγ）mRNA表达的变化,及二者与脑梗死体积的相天性、方法连续收集2010年7月-12月哈尔滨医科大学附属第二医院老年病科及神经内科就诊的发病3d以内的急性脑梗死患者72例及对照人群70例。用ELISA法测定两组患者血清中HMGB1,用实时RT—PCR法测定两组患者空腹周围血淋巴细胞PPAR3,mRNA的表达情况。根据脑梗死患者发病后48～72hCT检查结果,计算脑梗死体积。结果①梗死组患者PPARγmRNA表达水平（0．54±0．37）低于对照组（1．98±0．35）,血清HMGB1水平（12．7-4-6．1）μg／L高于对照组（2．2±0．8）μg/L,差异有统计学意义,P〈0．01。②脑梗死患者周围m淋巴细胞PPARγmRNA表达水平与血清HMGB1水平呈负相关,r=-0．843,P〈0．01。③经相关性分析,脑梗死患者PPARγmRNA表达水平与脑梗死体积呈负相关,r=-0．886,P〈0．01;脑梗死患者HMGBI水平和脑梗化体积呈正相关,r=0．847,P〈0．01。结论在脑梗死急性期,PPA脚和IHMGB1均参与脑缺血炎性反应,HMGBI及PPARγ即mRNA表达水平可反映急性脑梗死患者梗死体积的大小。     

Activated protein C inhibits high mobility group box 1 signaling in endothelial cells

A pathogenic role for high-mobility group box 1 (HMGB1) protein has been postulated in severe sepsis. Activated protein C (APC) is the only drug approved by the Food and Drug Administration for severe sepsis; however, its effect on HMGB1 signaling has never been investigated. Here, we monitored the effect of APC on the lipopolysaccharide-mediated release of HMGB1 and the HMGB1-mediated modulation of proinflammatory responses in HUVECs. APC potently inhibited the release of HMGB1 and down-regulated the adhesion of the monocytic cell line, THP-1, to HMGB1-activated endothelial cells. HMGB1 up-regulated proinflammatory responses by interacting with 3 pathogen-related pattern recognition receptors: TLR2 and TLR4 and the receptor for advanced glycation end products. APC not only inhibited HMGB1 release but also down-regulated the cell surface expression of all 3 HMGB1 receptors in endothelial cells. The protective effects of APC were mediated through endothelial cell protein C receptor (EPCR) and protease-activated receptor 1 (PAR-1). Interestingly, a thrombin derivative containing the Gla-domain of APC recapitulated all protective effects of APC with a 20- to 50-fold higher efficacy. These results suggest that the EPCR- and PAR-1-dependent protective effects of APC in severe sepsis may partially be mediated through the inhibition of HMGB1 signaling and that the chimeric thrombin mutant has potential therapeutic utility for severe sepsis.     

Elevated plasma levels of high mobility group box protein 1 in patients with HIV-1 infection

High mobility group box protein 1 (HMGB1) is a potent proinflammatory mediator. It has a dichotomic effect on HIV-1 replication in vitro but its role in vivo is unknown. Here we report the novel finding that plasma HMGB1 levels are elevated in HIV-1-infected patients, with the highest concentrations in patients with clinical complications. HMGB1 is likely to contribute to immunoactivation in HIV-1 infection in vivo.     

缺血性卒中患者血清生物标志物的应用现状

缺血性卒中具有高发病率、高致残率及高病死率的特点,血清中神经元特异性烯醇化酶、S-100β蛋白、细胞间黏附分子1、C反应蛋白、纤维蛋白原、D-二聚体及血清铁蛋白等生物标志物对缺血性卒中的辅助诊断、出血转化风险预测及预后判断等方面有重要的应用价值.该文对以上血清生物标志物在缺血性卒中中的应用作一综述.     

高迁移率族蛋白B1与炎症反应

早期主要将高迁移率族蛋白B1(high mobility group box1,HMGB1)作为非组蛋白DNA结合蛋白进行广泛研究.近年来发现HMGB1这一传统的DNA结合蛋白具有强大的致炎细胞因子活性.HMGB1可由活化的单核细胞、巨噬细胞、成熟树突细胞和活化的自然杀伤细胞等主动分泌,也可由坏死细胞被动释放,从而触发机体的免疫炎症反应.HMGB1本身也具有细胞毒性,全身给予HMGB1可以剂量依赖方式致小鼠死亡;巨噬细胞、中性粒细胞等暴露于HMGB1时可诱导致炎细胞因子肿瘤坏死因子和白介素1β等产生增多.HMGB1拮抗剂治疗对脓毒症和内毒素血症的致死性有显著的拮抗作用,潜在拓宽了临床危重感染患者的治疗时间窗.此外,HMGB1还参与轴突生长,且与肿瘤发生和预后相关.