汉坦病毒感染致血小板减少的机制

汉坦病毒主要感染血管内皮细胞,引起两种人类疾病,即肾综合征出血热和汉坦病毒心肺综合征,它们的共同特点是毛细血管广泛损伤,通透性升高。汉坦病毒感染者血小板数量严重减少,不仅与“外周破坏增加”有关,而且还可能与“血小板生成和功能障碍”有关。尽管汉坦病毒感染引起血小板减少的机制尚不完全明确,但近年也取得了一些重要进展。本文主要围绕血小板减少相关的两种机制展开讨论,旨在阐明汉坦病毒感染发病机制,为治疗肾综合征出血热的药物设计提供指导。     

肾综合征出血热生物标志物与病情预测模型研究进展

[摘要]　肾综合征出血热（hemorrhagic fever with renal syndrome, HFRS）是由汉坦病毒（Hantavirus, HV）感染引起的一种以发热、出血和急性肾损伤（acute kidney injury, AKI）为特征的自然疫源性疾病。HV感染可导致血管内皮细胞破坏,全身微血管弥漫性损伤,毛细血管通透性增加及血小板减少,部分患者可能产生细胞因子风暴并发展为毛细血管渗漏综合征,进而导致全身性水肿、低血容量性休克、AKI、凝血功能障碍甚至多器官功能障碍综合征。目前已有多项研究提出一些在HFRS病程中有实用价值的生物标志物,并构建了多种HFRS风险预测模型,部分生物标志物可能与HFRS的发病机制有关,且有助于临床医生早期预见性地评估病情,选择最佳治疗方案,提高HFRS的救治效果。     

肾综合征出血热抗病毒治疗及疫苗研发进展

肾综合征出血热(hemorrhagic fever with renal syndrome, HFRS)是由汉坦病毒感染引起的一种自然疫源性疾病,在世界范围内广泛流行,我国一直是流行高发区,患者占所有HFRS患者一半以上,其主要临床特征为发热、出血、低血压休克和肾脏损害,严重危害人类健康。尽管抗病毒治疗和疫苗免疫接种可以防治汉坦病毒感染,但目前尚无特效抗病毒药物。近年来,随着医学科技进步,汉坦病毒的抗病毒治疗和疫苗研发有了新的进展。本文基于近年体内外研究及临床试验结果,对HFRS抗病毒治疗和疫苗研发进展作一综述。     

肾综合征出血热患者T淋巴细胞亚群及IL-6、IL-10变化的研究

通常认为，在肾综合征出血热（HFRS）发病过程中，汉坦病毒感染作为致病的始动因素．激发了机体的免疫应答，导致机体免疫功能紊乱。我们旨在通过对重要免疫学指标T细胞亚群、IL-6、IL-10及其与病期和病型的动态性及相关性研究．以揭示免疫功能紊乱在HFRS发病机制中的作用。     

肾综合征出血热患者外周血循环内皮细胞、cd61、HSP70的表达分析

正肾综合征出血热(HFRS)临床主要表现为肾功能衰竭、低血压休克、出血、发热等,是由汉坦病毒感染所致的急性传染病,现目前缺乏此病的确切发病机制。相关研究显示,汉坦病毒感染可广泛性损伤小血管及全身毛细血管~([1])。当细胞受到汉坦病毒感染时,CD61起着独立介导性作用,在病理或生理条件下会从循环状态中得到循环内皮细胞,可在活体中持续不断地检测出特异性,对活体毛细血管的受损程度做出直接反应~([2])。当机体遭受病毒感染时,会伴有自身保护性应     

汉坦病毒感染早期IRF-7及RANTES的表达

摘要：为检测汉坦病毒感染人淋巴细胞后人正常T 细胞表达分泌调节活化因子（RNATES）和干扰素调节因子-7（IFR-7）的情况,并为深入探讨其可能的致病机制奠定基础,本研究用汉滩病毒感染人淋巴细胞系LLC,取感染后不同时间点的细胞提取总RNA,半定量RT-PCR检测感染细胞中IFR-7及RANTES mRNA的变化情况。结果显示,在汉滩病毒感染人淋巴细胞早期,可诱导IRF-7和RNATES基因的转录,并随着感染时间的延长表达持续上调。上述结果说明,汉坦病毒可以感染人淋巴细胞,并在感染早期持续上调RNATES和IRF-7表达。这为进一步深入探讨汉坦病毒的致病机制和寻找HFRS的治疗药物靶位奠定基础。     

肾综合征出血热患者血浆细胞因子的动态变化

肾综合征出血热(HFRS)是由汉坦病毒(hantavirus)引起的以啮齿类动物为主要传染病的自然疫源性疾病，我国是HFRS的高发地区之一，其长期危害我国人民的生命健康。研究表明过度活化的免疫应答和炎症反应引起的“细胞因子风暴”是导致HFRS致病的机制之一。本文拟对HFRS患者中各种细胞因子的动态变化进行综述。     

阿魏酸哌嗪联合血液透析对肾综合征出血热急性肾衰竭患者血清sICAM-1、E-选择素、L-选择素的影响分析

<正>肾综合征出血热(HFRS)主要由汉坦病毒感染导致,是一种急性传染病。病情严重且进展速度快,具有较高的病死率~([1])。病原体侵入人体后可引发血管内皮细胞受损,继而诱发小动脉、小静脉及毛细血管损伤,最终导致血管内皮变性、肿胀、坏死,出现全身各器官损伤甚至衰竭~([2])。急性肾衰竭是HFRS最常见的并发症,也是对患者预后影响最为严重的并发症之一。HFRS的常规治疗方案为血液透析,是减轻肾脏负担、     

肾综合征出血热患者血清新蝶呤、单核细胞趋化蛋白-1和白细胞介素-12等细胞因子的变化及其临床意义

肾综合征出血热(HFRS)发病机制迄今未完全阐明,多数研究表明汉坦病毒并不直接致病,为此,我们研究了血清新蝶呤、单核细胞趋化蛋白-1(MCP-1)、IL-12、IFNγ与IL-10的变化,以了解单核细胞激活及Th1/Th2极化状态与HFRS病情的关系.     

肾综合征出血热患者IL-15和sICAM-1的动态变化

肾综合征出血热 (HFRS)是由汉坦病毒 (HV )引起的一种自然疫源性疾病 ,其发病机制至今尚未完全阐明。一般认为 ,HV作为重要的始动因子 ,一方面病毒感染能导致感染细胞功能和结构的损害 ,另一方面病毒感染诱发人体的免疫应答和各种细胞因子的释放 ,既有清除感染病原、保护机体的作用 ,又有能引起机体组织损伤的不利作用。细胞因子调节是机体免疫调节的一种重要形式 ,在参与机体免疫调节的同时还可直接造成机体的病理损伤。本实验应用酶联免疫检测法 (ELISA)检测了HFRS患者发病早期、极期及恢复期血清的IL 15和sICAM 1(人可溶性细胞…     

Mechanisms of disease in Hantavirus infection: pathophysiology of hemorrhagic fever with renal syndrome.

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral disease that occurs over wide areas of Europe and Asia. Hantaviruses are the cause of this syndrome. The hallmark of HFRS is the triad of fever, hemorrhage, and renal failure. In its severe form it is associated with significant mortality. The syndrome evolves through five phases: febrile, hypotensive, oliguric, diuretic, and convalescent. The central physiologic derangement in HFRS is vascular dysfunction, manifested by impaired vascular tone and increased vascular permeability. The systemic effects of this dysfunction account for the occurrence of hypotension and shock, while local effects are probably important in the development of renal failure. Shock in HFRS has distributive and oligemic features, while renal failure has features of acute tubular necrosis. Hemorrhage is a consequence of vascular injury and a deficit of functional platelets. Vascular and platelet dysfunction are both compounded by uremia. Disseminated intravascular coagulation contributes to hemorrhage in some patients. Although hantaviruses are infectious for endothelial cells and may cause direct injury, a large body of evidence suggests that immune mechanisms play an important role in the pathogenesis of HFRS.     

肾综合征出血热流行过程及其影响因素研究进展

肾综合征出血热（hemorrhagic fever with renal syndrome, HFRS）是由汉坦病毒（hantavirus）感染引起的一种乙类传染病,可引发急性肾损伤,病死率较高。汉坦病毒型别与选择性宿主转换和地区适应密切相关,并由此不断以基因重组等方式进化,不同型别汉坦病毒所致疾病严重程度不同。全球环境变化及宿主动物习性改变加速了汉坦病毒基因组变异;同时,我国大规模土地改造、基础设施建设也使人群与病毒宿主和疾病传播媒介的接触机会增加,一定程度上增大了人群患病风险。本文综述了肾综合征出血热流行过程的主要特征及其相关影响因素,为有效防控该疾病的发生和流行提供参考依据。     

Innate and adaptive immune responses against human Puumala virus infection: immunopathogenesis and suggestions for novel treatment strategies for severe hantavirus‐associated syndromes

Two related hyperinflammatory syndromes are distinguished following infection of humans with hantaviruses: haemorrhagic fever with renal syndrome (HFRS) seen in Eurasia and hantavirus pulmonary syndrome (HPS) seen in the Americas. Fatality rates are high, up to 10% for HFRS and around 35%–40% for HPS. Puumala virus (PUUV) is the most common HFRS‐causing hantavirus in Europe. Here, we describe recent insights into the generation of innate and adaptive cell‐mediated immune responses following clinical infection with PUUV. First described are studies demonstrating a marked redistribution of peripheral blood mononuclear phagocytes (MNP) to the airways, a process that may underlie local immune activation at the site of primary infection. We then describe observations of an excessive natural killer (NK) cell activation and the persistence of highly elevated numbers of NK cells in peripheral blood following PUUV infection. A similar vigorous CD8 Tcell response is also described, though Tcell responses decline with viraemia. Like MNPs, many NK cells and CD8 T cells also localize to the lung upon acute PUUV infection. Following this, findings demonstrating the ability of hantaviruses, including PUUV, to cause apoptosis resistance in infected target cells, are described. These observations, and associated inflammatory cytokine responses, may provide new insights into HFRS and HPS disease pathogenesis. Based on similarities between inflammatory responses in severe hantavirus infections and other hyperinflammatory disease syndromes, we speculate whether some therapeutic interventions that have been successful in the latter conditions may also be applicable in severe hantavirus infections.     

2007年云南省汉坦病毒宿主动物及其基因分型研究

目的掌握云南省肾综合征出血热（HFRS）流行病学特点、汉坦病毒（HV）宿主动物及基因型分布,为防治提供科学依据。方法收集2007年全省HFRS疫情资料;居民区采用笼夜法捕鼠,野外采用夹夜法捕鼠;鼠肺组织标本用直接免疫荧光法检测HV抗原,用RT-PCR法检测HV核酸及分型。结果2007年全省共报告HFRS病例14例,死亡1例,年发病率为0.02/10万,病死率为7.14%。主要发病地区为大理和楚雄州。2007年在泸西、五华、祥云、玉龙、古城、河口、麻栗坡、泸水和隆阳区（县）捕获鼠类21种1 390只,其中居民区以黄胸鼠和褐家鼠为优势鼠种,野外以大绒鼠、中华姬鼠为优势鼠种。鼠间HV总带病毒率为4.17%,阳性鼠种为大林姬鼠、褐家鼠、大绒鼠、高山姬鼠、黄胸鼠、中华姬鼠和卡氏小鼠,带病毒率依次为9.09%（1/11）,7.52%（10/133）,7.35%（23/313）,5.71%（2/35）,2.57%（13/505）,2.38%（2/84）,2.22%（2/9）;用RT-PCR法检测HV抗原阳性鼠肺标本58份,阳性29份,其中汉城型阳性16份,汉滩型阳性13份;汉城型主要带毒鼠种为褐家鼠和黄胸鼠,汉滩型带毒鼠种主要为大绒鼠、高山姬鼠和中华姬鼠。结论调查地区广泛存在以褐家鼠为主要传染源的家鼠型HFRS疫源地,也存在以大绒鼠为主要传染源的野鼠型HFRS疫源地;存在汉城型和汉滩型病毒的流行,汉滩型病毒具有多种宿主动物的特点,在国内具有特殊性。     

Central Nervous System and Ocular Manifestations in Puumala Hantavirus Infection

Puumala hantavirus (PUUV), carried and spread by the bank vole (Myodes glareolus), causes a mild form of hemorrhagic fever with renal syndrome (HFRS) called nephropathia epidemica (NE). Acute high fever, acute kidney injury (AKI), thrombocytopenia, and hematuria are typical features of this syndrome. In addition, headache, blurred vision, insomnia, vertigo, and nausea are commonly associated with the disease. This review explores the mechanisms and presentations of ocular and central nervous system involvement in acute NE.     

肝功指标判断汉坦病毒所致肝损害的临床价值

目的探讨常用肝功能指标判断汉坦病毒所致肝损害的临床价值。方法回顾性分析367例肾综合征出血热(HFRS)患者肝功能指标、病情及治疗结局的关系。结果HFRS患者ALT、AST、TBIL及白蛋白异常分别占73.84%(271/367)、79.84%(293/367)、13.35%(49/367)和44.41%(163/367)。HFRS不同临床型间ALT、AST和TBIL差异有统计学意义(P<0.001),而白蛋白各型间差异无统计学意义(P>0.05)。结论汉坦病毒易于引起肝脏损害,肝损害程度与病情、预后有关;ALT、AST及TBIL是反映肝脏损害程度的重要指标;而白蛋白不能作为汉坦病毒肝损害程度的判断指标。     

The Association between Hantavirus Infection and Selenium Deficiency in Mainland China

Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses and transmitted by rodents is a significant public health problem in China, and occurs more frequently in selenium-deficient regions. To study the role of selenium concentration in HFRS incidence we used a multidisciplinary approach combining ecological analysis with preliminary experimental data. The incidence of HFRS in humans was about six times higher in severe selenium-deficient and double in moderate deficient areas compared to non-deficient areas. This association became statistically stronger after correction for other significant environment-related factors (low elevation, few grasslands, or an abundance of forests) and was independent of geographical scale by separate analyses for different climate regions. A case-control study of HFRS patients admitted to the hospital revealed increased activity and plasma levels of selenium binding proteins while selenium supplementation in vitro decreased viral replication in an endothelial cell model after infection with a low multiplicity of infection (MOI). Viral replication with a higher MOI was not affected by selenium supplementation. Our findings indicate that selenium deficiency may contribute to an increased prevalence of hantavirus infections in both humans and rodents. Future studies are needed to further examine the exact mechanism behind this observation before selenium supplementation in deficient areas could be implemented for HFRS prevention.