高迁移率族蛋白1与心血管疾病关系概述

高迁移率族蛋白1(HMGB1)是典型的核内非组蛋白,可以通过活化细胞的主动分泌和受损坏死细胞的被动释放两种方式,进入胞外并介导炎性反应,为一种重要的炎性介质和促炎细胞因子。HMGB1在多种心血管疾病中高表达,已在《高迁移率族蛋白1在炎症和心血管疾病中的作用》[1]中对其参与炎症反应的过程进行了详细阐述,并且指出了其在损伤与修复中的矛盾作用。随着对HMGB1研究的深入,对其在心血管系统中的作用有了进一步认识,该文将重点对其在动脉粥样硬化、心肌梗死、缺血再灌注、心力衰竭等几种常见心血管病中所发挥的作用进行概述。     

高迁移率族蛋白B1在心血管系统疾病中的作用

高迁移率族蛋白(HMG)于1973年首次在牛胸腺中被提取和鉴定,因其分子量小在聚丙烯酰胺凝胶电泳中迁移率快而得名,是一类广泛分布于高等真核生物细胞核内的非组DNA结合蛋白.大量文献报道,其家族成员之一的HMGB1在炎症性疾病的发病机制中发挥重要作用.本文对近来HMGB1在心血管系统疾病研究作一综述.     

高迁移率族蛋白-1与脑出血

高迁移率族蛋白(high mobility group box 1,HMGB1)是一种广泛分布于真核细胞中高度保守的非组DNA结合蛋白.它是一种重要的促炎性细胞因子,参与多种病理生理学过程,例如炎症和神经血管生成等.在脑出血早期,HMGB1可诱发炎性反应、神经元坏死、脑水肿等继发性脑损伤;在脑出血晚期,HMGB1可促进血管神经发生,进而改善神经功能.将来,HMGB1有可能成为脑出血的新治疗靶点.     

晚期炎症介质高迁移率族蛋白1与重症急性胰腺炎

重症急性胰腺炎（SAP）死亡率高，预后差。SAP的发生与大量细胞因子级联反应引起的全身炎症反应综合征（SIRS）密切相关。SIRS是造成多器官功能不全综合征（MODS）的重要原因。近10余年临床研究显示，早期释放的炎症因子如TNF—α、IL-1等均在模型建立后迅速升高至峰值，并迅速下降，而此时炎症反应仍在继续，并且临床应用TNF—α、IL-1受体拮抗剂并未取得显效果，提示可能存在晚期炎症介质参与病理反应。高迁移率族蛋白1（highmobility group box 1，HMGB1）是一类广泛存在于真核细胞内的非组核蛋白，近年来有关HMGB1的报道逐年增加。本就此做一简要综述。[第一段]     

高迁移率族蛋白B1与脑缺血

高迁移率族蛋白B1(high mobility group box 1,HMGB1)是高迁移率族蛋白家族成员之一.细胞外HMGB1和细胞表面受体--晚期糖基化终产物受体(receptor for advanced glycation endproduct,RAGE)、Toll样受体2(toll like receptor 2,TLR2)和Toll样受体4(toll like receptor 4,ILR4)结合,与其他促炎介质协同作用,促进炎症级联反应.脑缺血后,过度表达的HMGB1参与了炎症反应、神经元凋亡等病理生理学过程.     

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.     

高迁移率族蛋白 B1与缺血性卒中

高迁移率族蛋白 B1(high mobility group protein box 1, HMGB1)是一种典型的非组蛋白,在细胞核内具有多种功能。近年来的研究表明,HMGB1可释放到细胞外发挥广泛的细胞学效应。缺血性卒中是发病率和致残率最高的疾病之一。越来越多的证据表明,HMGB1在缺血性卒中的发生和发展过程中起到多种重要作用。文章就 HMGB1在缺血性卒中中的作用进行了综述。     

高迁移率族蛋白B1在肝脏疾病发生中的作用

高迁移率族蛋白B1（HMGB1）是含量丰富的非组蛋白染色体结合蛋白,在细胞损伤和炎症反应时可通过主动分泌和被动释放移位到细胞浆和细胞外。近年研究提示HMGBl可作为一种炎症因子和内源性损伤相关分子模式被其受体识别而促进肝脏炎症、损伤和纤维化发生信号,并参与肝脏肿瘤发生和对肿瘤的免疫反应。本文对这些方面的研究进展作一简要综述。     

高迁移率族蛋白B1在肠道炎症和肿瘤中的作用

高迁移率族蛋白B1(high mobility group box 1protein,HMGB1)由Wang等[1]在1999年发现,在炎症晚期的作用已被大量的研究所证实,HMGB1不仅在脓毒症的致死过程中发挥重要作用,还与风湿性关节炎、失血性休克、慢性肝病、恶性肿瘤、缺血再灌注等发病有关[2]。HMGB1是细胞核中一种典型的低分子非组蛋白,通过与DNA结合稳定核小体结构,使p53、类固醇激素,NF-κb等多种分子与     

高迁移率族蛋白B1（HMGB1）和肿瘤

HMGB1是一种非常古老的核蛋白,在悠久的进化史中具有高度保守的特点,哺乳动物中HMGB1具有99%的同源特质[1]。HMGB1作为一种核蛋白可以稳定核小体,调节多种基因的转录,同时作为一种炎症因子,它可被多种炎症细胞释放或分泌,参与多种疾病的发生,发展和转归,     

高迁移率族蛋白B1-Toll样受体途径与炎症性肠病

高迁移率族蛋白B1(HMGB1)广泛存在于体内各种细胞中,在组织损伤时由坏死细胞被动释放或由免疫细胞受病原体产物刺激后主动释放至胞外,发挥促炎细胞因子作用,参与多种炎症性疾病的发生、发展和转归。Toll样受体(TLRs)是HMGB1的主要受体之一,HMGB1与TLR2、TLR4相互作用,最终激活NF-κB,导致大量炎症因子释放,通过正反馈作用放大炎症反应。近年研究表明HMGB1-TLR途径与炎症性肠病的发生、发展有关,本文就两者间的关系作一综述。     

高迁移率族蛋白B1抗体对结肠炎小鼠结肠黏膜的保护作用

背景:我国溃疡性结肠炎(UC)发病率明显上升,但目前尚无满意的治疗方法,因此研究其发病机制并寻求新的治疗途径具有重要意义。目的:研究高迁移率族蛋白B1(HMGB1)抗体对结肠炎小鼠结肠黏膜的影响。方法:36只BALB/c小鼠随机分为正常对照组、结肠炎模型组和HMGB1抗体治疗组,后两组以3%葡聚糖硫酸钠(DSS)制备小鼠结肠炎模型,HMGB1抗体治疗组小鼠腹腔注射HMGB1抗体。实验第7d,处死小鼠。行结肠组织学评分,测定结肠通透性,分别以RT-PCR和蛋白质印迹法检测结肠组织HMGB1 mRNA和蛋白表达。结果:与正常对照组相比,结肠炎模型组小鼠结肠组织学评分、结肠通透性以及HMGB1 mRNA和蛋白表达显著增高(P0.05)。与结肠炎模型组相比,HMGB1抗体治疗组小鼠结肠组织学评分、结肠通透性和HMGB1蛋白表达显著降低(P0.05)。结论:HMGB1参与了结肠炎小鼠的炎症反应过程,HMGB1抗体可有效抑制结肠炎小鼠结肠组织HMGB1表达,改善肠黏膜屏障功能,从而对UC结肠黏膜损伤起有明显保护作用。     

急性冠脉综合征患者高迁移率族蛋白B1和超敏C反应蛋白的变化及意义

目的观察急性冠脉综合征（ACS）患者血清高迁移率族蛋白B1（HMGB1）水平和超敏C反应蛋白（hs-CRP）水平变化,探讨其与冠状动脉病变程度及短期预后的关系。方法选择ACS患者共57例,其中急性心肌梗死（AMI）30例,不稳定型心绞痛（UA）27例;单支病变33例,多支病变24例。同时选择26例健康对照组。采用酶联免疫吸附试验（ELISA）法测定所有受试者血清HMGB1;并同时测定hs-CRP。结果 ACS组患者血清HMGB1及hs-CRP浓度均高于健康对照组（P〈0.05）,AMI与UA两组间HMGB1浓度无明显统计学意义（P〉0.05）;ACS组患者血清HMGB1与hs-CRP水平呈正相关（γ=0.343,P〈0.05）;多支病变组HMGB1浓度显著高于单支病变组（P〈0.05）。发生MACE的患者HMGB1及hs-CRP浓度均显著高于未发生MACE患者,（P〈0.05）。结论 1、ACS组患者血清HMGB1水平及hs-CRP水平均显著升高。2、ACS组患者血清HMGB1水平与hs-CRP水平呈正相关。3、ACS患者多支病变组血清HMGB1水平显著高于单支病变组。4、血清HMGB1水平及hs-CRP水平可能是预测AMI组患者MACE的危险因素的指标。     

血清高迁移率族蛋白1水平与类风湿关节炎临床指标的相关性

目的通过检测活动性类风湿关节炎(rheumatoid arthritis,RA)患者血清高迁移率族蛋白1(high mobility group box protein 1,HMGB1)表达水平,探讨HMGB1与RA患者疾病活动性、自身抗体及临床指标的相关性。方法采用双抗体夹心酶联免疫吸附试验测定67例活动性RA患者和21位健康对照者血清HMGB1水平。收集RA患者的同期临床资料并测定相关实验室指标:疼痛视觉模拟评分(visual analog scale,VAS)、疲乏VAS、肿胀关节数、压痛关节数、患者对疾病总体状况的VAS(patient′s global assessment,PGA)、健康评估问卷(health assessment questionnaire,HAQ)、疾病活动评分28(dise aseactivity score28,DAS28)、血沉、C-反应蛋白、类风湿因子-IgM、抗环瓜氨酸肽抗体等,分析以上指标与血清HMGB1的相关性。结果活动性RA组血清HMGB1中位数为8.7ng/ml,四分位间距为16.59ng/ml;健康对照组血清HMGB1中位数为3.47ng/ml,四分位间距为7.43ng/ml,活动性RA组血清HMGB1表达水平显著高于健康对照组,两组间比较差异有统计学意义(P0.01)。活动性RA患者血清HMGB1表达水平与类风湿因子呈正相关(P0.01),与疼痛VAS评分、疲乏VAS评分、肿胀关节数、压痛关节数、PGA、HAQ、DAS28评分及血沉、C-反应蛋白、抗环瓜氨酸肽抗体无相关性(P0.05)。结论活动性RA患者血清HMGB1表达水平较健康对照组显著升高,但可能与疾病活动无关。     

High Mobility Group Box 1 Protein as an Auxiliary Biomarker for Dengue Diagnosis

Despite the availability of many methods for rapid and early diagnosis of dengue, there is still a need to develop new approaches that not only combine low cost, specificity, and sensitivity, but also are capable of accurately detecting secondary infection in the early stages of the disease. We report the potential of the high mobility group box 1 protein as an auxiliary biomarker for early dengue diagnosis. We tested a 205-sample serum panel that included negative and positive samples from primary and secondary dengue cases, as well as samples from patients with dengue-like symptoms. We observed that high mobility group box 1 protein was generally detected only in dengue-positive samples for persons with primary and secondary infections. These results highlight the possibility of using this endogenous molecule as an auxiliary biomarker to aid in dengue detection and improve current methods for early diagnosis of dengue.Dengue infection affects at least 50 million persons per year in tropical and subtropical regions. Severe cases of dengue are responsible for more than 500,000 hospitalizations and thousands of deaths, which occur principally in children.¹ Dengue infection presents as a wide range of clinical symptoms that varies from an asymptomatic infection to a self-limiting, mild-fever disease (dengue fever [DF]) to a severe and potentially fatal hemorrhagic disorder (dengue hemorrhagic fever/dengue shock syndrome).² A rapid and accurate diagnosis of dengue in the first days after the onset of symptoms is a critical step in dengue surveillance and outbreak control.Detection of viral antigens is a simple and a reliable method that is commonly used. However, during a secondary infection, the sensitivity of this method may be significantly compromised because of pre-existing immunocomplexes. Precise detection of secondary infection is important because of the risks it represents for development of severe dengue. Early detection of severe disease has the potential to decrease morbidity and mortality, and new biomarkers that can reliably distinguish hemorrhagic cases are urgently needed.³ Although there are many commercial kits that are based on the early detection of dengue virus (DENV) infection, there is still a need for new approaches that combine specificity, sensitivity, rapid results, ease of use, and low cost for the diagnosis of primary or secondary DENV infection in the first few days after the appearance of symptoms.³The high mobility group box 1 (HMGB1) was first described as a non-histone nuclear protein that binds and bends DNA and thus acts as a nuclear remodeling factor to facilitate the physical interactions between DNA and many others proteins.⁴ Although HMGB1 is usually found in the cell nucleus, it can be translocated to the cytoplasm or even be secreted into the extracellular milieu under some circumstances.⁵ The secretion of HMGB1 occurs through at least two pathways: passively from necrotic cells and/or actively by activated immune cells.^6,7 Once outside the cell, it acts as a soluble mediator that plays an important role as a pro-inflammatory cytokine.⁸ The involvement of HMGB1 in DENV infection was first observed in DENV-infected epithelial cells undergoing necrosis, which passively released this molecule into the extracellular milieu.⁹ Another report showed that DENV-infected dendritic cells actively translocate HMGB1 to the cytoplasm or even secrete it.¹⁰ In our previous study, we demonstrated that circulating levels of HMGB1 in serum of DENV-infected patients were significantly increased, and the highest levels occurred during the first days after appearance of symptoms and in patients with a secondary infection.¹¹ We investigated the potential of the HMGB1 protein as an auxiliary biomarker for early dengue diagnosis to detect either primary or secondary infection without the risk of immunocomplex assembly.We used a 205-sample serum panel that included negative samples (healthy blood donors [HD]) that were obtained from the Cuban National Blood Bank and positive samples that were obtained from Dengue Serum Bank at the Pedro Kouri Tropical Medicine Institute of Havana, Cuba. All positive samples were obtained from adult patients with non-hemorrhagic cases of dengue who had been classified according to the type of infection (primary or secondary) and by the number of days after symptom onset during which samples were collected (day 0 was considered the first day of symptoms (*

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。     

X盒结合蛋白1在高迁移率族蛋白B1

目的　探讨活化的X盒结合蛋白1（XBP1）在高迁移率族蛋白B1（HMGB1）诱导人脐静脉血管内皮细胞凋亡中的作用及机制。方法　体外培养人脐静脉血管内皮细胞,将其分为正常对照组、HMGB1刺激组和慢病毒干扰＋HMGB1刺激组（即XBP1基因被沉默后加入HMGB1）。采用RT-PCR检测剪切型XBP1（sXBP1）的基因表达水平,Western　blot检测Caspase-3的蛋白表达水平,细胞荧光染色检测内皮细胞凋亡。结果　与正常对照组比较,HMGB1刺激组sXBP1的基因表达水平增加,Caspase-3的蛋白表达水平明显升高,细胞凋亡率明显增加（P均＜0.05）;与正常对照组比较,慢病毒干扰＋HMGB1刺激组sXBP1的基因表达水平无明显改变,Caspase-3的蛋白表达水平、细胞凋亡率差异无统计学意义（P>0.05）。与HMGB1刺激组比较,慢病毒干扰＋HMGB1刺激组sXBP1的基因表达水平降低,Caspase-3的蛋白表达水平降低,细胞凋亡率降低（P均＜0.05）。结论　XBP1对HMGB1诱导内皮细胞凋亡至关重要。     

高迁移率蛋白1、Toll受体与动脉粥样硬化的关系

动脉粥样硬化是血管慢性增殖性炎症过程,也是对血管损伤的反应和修复过程。高迁移率蛋白1作为一种重要的晚期炎症介质,参与多种炎性疾病的发生发展。Toll样受体是最重要的先天免疫系统的模式识别受体识别微生物的病原相关分子模式。高迁移率蛋白1可能通过Toll样受体激活炎性反应,参与动脉粥样硬化的发生和发展。     

Thalassaemia major and infectious risk: High Mobility Group Box‐1 represents a novel diagnostic and prognostic biomarker

High mobility group box ‐1 (HMGB1) represents a common causal agent for various types of diseases, including infective pathologies. This study aimed to investigate the role of HMGB1 in β‐thalassemia major (TM) by evaluating its diagnostic and prognostic role. Fifty‐one TM patients and 30 healthy subjects (HS) were enrolled. Receiver operating characteristics (ROC) analysis was employed to calculate the area under the curve (AUC) for HMGB1 to determine the best cut‐off values capable of identifying infectious episodes. Adjusted risk estimates for infective events were calculated using univariate followed by multivariate Cox proportional hazard regression analysis. Serum HMGB1 levels were higher in TM patients than in HS (14·6 ± 8·7 vs. 2·08 ± 0·9 ng/ml, P < 0·0001). Patients who underwent splenectomy were characterized by lower levels of HMGB1, when compared with patients with an intact spleen (10·2 ± 8 vs. 19·1 ± 7 ng/ml, P = 0·004). ROC analyses revealed an AUC for serum HMGB1 of 0·801, with a sensitivity and specificity of 92·3% and 68·2% to detect an infectious episode. Low HMGB1 levels predicted high risk of infective events (HR: 0·81; P = 0·006). HMGB1 represents a prognostic marker for TM patients and a predictive factor for infectious events.