EVIHVR: A platform for analysis of expression, variation and identification of human virus receptors

Motivation:Virus receptors are presented on the cell surfaces of a host and are key for viral infection of host cells.However,no unified resource for the study of viral receptors is currently available.Results:To address this problem,we built EVIHVR,a platform for analyzing the expression and variation,and for the identification of human virus receptors.EVIHVR provides three functions:(1)Receptor expression function for browsing and analyzing the expression of human virus receptors in various human tissues/cells;(2)Receptor gene polymorphism function for analyzing the genetic polymorphism of human virus receptors in different human populations and human tissues;and(3)Predict receptor function for identifying potential virus receptors based on differential expression analysis.EVIHVR can become a useful tool for the analysis and identification of human virus receptors.

Study on PRRSV Receptor Genes Differential Expression in Lung Tissues in Different Breeds of Pigs after Infecting with HP-PRRSV

[ Objective] In order to study the susceptibility molecular mechanism of highly pathogenic porcine reproductive and respiratory syndrome virus （ HP- PRRSV） JXA1 isolate on Tibetan pig, Zangmei pig and Yorkshire pig. [ Method ] In the study, real-time quantitative RT-PCR method was established to compare and analyze the differential expression of five porcine reproductive and respiratory syndrome virus （PRRSV） receptor genes （HSPG2, SIGLEC1, CD163, VIM and NMMHC-H A） in lung tissues in Tibetan pig, Zangmei pig and Yorkshire pig before the challenge and at the 4th ,7th and 14th days after the challenge with JXAI isolate. [ Results ] HSPG2 expression in Tibetan pig lung tissues increased significantly at the 4th and 14th days after the challenge with JXAI （ P 〈 0.05 ）, while decreased significantly at the 7th day after the challenge （P 〈 0.05 ）, HSPG2 expression in Zangmei pig lung tissues increased significantly at the 14th day after the challenge （P〈0.05）. SIGLECl expression in Tibetan pig lung tissues increased significantly at the 4th and 14th days after the infection（P 〈 0.05 ）, while SIGLEC 1 expression in Yorkshire pig decreased significantly at the 4th, 7th and 14th days after the challenge （P 〈0. 05 ）. CD163 expression in lung tissues of Tibetan pig and Zangmei pig both increased significantly at the 14th day after the challenge （P 〈 0.05 ）, while CD163 expression in lung tissues of Yorkshire pig decreased significantly at the 7th and 14th days after the challenge （ P 〈 0. 05 ）. VIM expression in lung tissues of Tibetan pig increased significantly at the 7th day after the challenge （ P 〈 0. 05 ）, while which of Yorkshire pig at the 7th day after the challenge decreased significantly （ P 〈 0. 05 ）. NMMHC-II A expression in lung tissues of Zangmei pig increased significantly at the 4th day after the challenge （ P 〈 0. 05 ）, and which of Yorkshire pig increased significantly at the 4th and 14th days after the challenge （P 〈 0. 05 ）. [ Conclusion] SIGLEC1 and VIM genes might be the potential key genes affecting the susceptibility of JXA1 isolate on Tibetan pig, Zangrnei pig and Yorkshire pig. Key words JXA1 isolate; Tibetan pig; Zangmei pig; Yorkshire pig; Porcine reproductive and respiratory syndrome virus receptor genes; Differential expression

FLT-1、YKL-40在呼吸道合胞病毒阳性患儿血清中的表达水平及其临床意义

【目的】探讨人血管内皮生长因子受体-1(FLT-1)、人甲壳质酶蛋白40(YKL-40)在呼吸道合胞病毒(RSV)阳性患儿血清中的表达水平及其临床意义。【方法】选择2019年3月至2021年4月西安医学院附属宝鸡医院收治的82例RSV阳性患儿,所有患儿均给予重组人干扰素α-2b注射治疗,根据临床疗效将RSV阳性患儿分为有效组和无效组。收集两组患儿的一般资料,采用Logistic多因素回归分析RSV阳性患儿临床疗效的影响因素,采用受试者工作特征(ROC)曲线分析血清FLT-1、YKL-40水平对RSV阳性患儿临床疗效的预测价值。【结果】本研究82例RSV阳性患儿中,有效组59例(71.95%),无效组23例(28.05%);有效组患儿年龄大于无效组,FLT-1、YKL-40水平均低于无效组,差异均具有统计学意义(P<0.05);多因素回归分析结果显示:患儿年龄小及血清FLT-1、YKL-40水平高均是RSV阳性患儿治疗无效的危险因素(P<0.05);ROC曲线分析结果显示:血清FLT-1及YKL-40水平预测RSV阳性患儿临床疗效的ROC曲线下面积(AUC)分别为0.803(95%CI:0.710~0.895)、0.778(95%CI:0.669~0.888)。【结论】血清FLT-1及YKL-40水平高的低龄RSV阳性患儿更易出现临床疗效不佳,二者对RSV阳性患儿的临床疗效具有一定的预测价值。

呼吸道合胞病毒感染对豚鼠β肾上腺素能受体的影响

目的 :研究呼吸道合胞病毒 (RSV)感染豚鼠后不同时期 ,豚鼠肺组织 β肾上腺素能受体数量及亲和力的变化。方法 :病毒接种组与对照组分别于接种后不同时间进行肺组织光镜、电镜检查 ,并用放射性配基结合分析法测定肺组织 β受体的变化。 结果 :(1)RSV接种后 5 - 7d ,豚鼠肺组织均出现毛细支气管炎、肺炎的病理改变 ,14d基本恢复正常。 (2 )病毒接种组β受体平衡解离常数 (Kd)在RSV接种后 3d高于对照组 (P <0 .0 1) ,5 - 7d达高峰(P <0 .0 1) ,以后逐渐下降 ,接种后 14、2 1d与对照组无显著差异 (P >0 .0 5 )。β受体最大结合容量 (Bmax)在RSV接种后无明显改变。结论 :(1)豚鼠鼻腔接种RSV病毒悬液可以建立毛细支气管炎、肺炎的动物模型。 (2 ) β受体亲和力下降是RSV感染引起气道高反应性及喘息性疾病的机制之一。

植物病毒病媒介昆虫的传毒特性和机制研究进展

植物病毒病是农作物的"癌症",至今缺少有效的防治方法。目前已知80%的植物病毒病依赖于媒介昆虫传播,而媒介昆虫对植物病毒的传播是一个昆虫、病毒、寄主植物互作的过程,历经获毒、持毒和传毒等多个阶段,昆虫体内一系列病毒受体或蛋白参与了这个过程。昆虫传播病毒的方式有口针携带式、前肠保留式和体内循环式3类,它们各自对应的持久性为非持久性、半持久性和持久性,不同昆虫获取这3类病毒的获毒时间、在体内存留位置和传毒时间也各不相同。这个过程受到媒介昆虫的性别及龄期、寄主植物、环境条件、昆虫体内共生菌等多种因素的影响。与之相关的蛋白主要有病毒衣壳蛋白(CP)、次要衣壳蛋白(CPm)、GroEL蛋白、辅助因子(HC)和下颚口针蛋白等。近年来对植物病毒基因组的研究也取得了很大的进展,对昆虫传毒机制的研究正受到越来越广泛的关注。本文综述了近年来该领域内的相关研究进展,包括昆虫传播植物病毒的传毒方式、影响传毒效率的因素、传毒机制特别是昆虫体内与病毒传播可能相关的受体等。

激素对重型肝炎患者血清TNFα和sIL-2R的影响

目前国内外对肾上腺皮质激素治疗重型肝炎的利弊存在一定的争议.但 Muto et al 报告,1993年从日本各大中心收集的数百例暴发性病毒性肝炎(相当于我国的急性重型肝炎),用激素疗法者占52.7%～61.2%.我们应用激素短程疗法治疗病毒性重型肝炎亦取得了一定的疗效,为进一步探讨其疗效机制,我们于1998-03/1999-06,对13例激素治疗的病毒性重型肝炎患者血清 TNFα和 sIL-2R 水平进行了观察.

2011年中国北方H9N2亚型禽流感病毒分离株HA基因进化分析及受体结合性检测

为了解近期中国北方禽源H9N2亚型禽流感病毒(AIV)流行规律及分子遗传进化特征,本实验对2011年在中国北方家禽中分离到的11株H9N2亚型AIV通过RT-PCR扩增病毒的HA基因片段,进行测序及遗传进化分析,并对这些病毒的受体结合性进行了检测。结果表明:11株H9N2亚型AIV分离株的HA基因在HA1和HA2的氨基酸裂解位点均为PSRSSR/GLF基序,符合低致病性病毒株氨基酸序列特征。多数病毒HA潜在糖基化位点为8个,所有分离株病毒的受体结合位点226位均为L,经红细胞受体结合性试验验证表明这些病毒均同时具有α-2,3和α-2,6受体结合特性,表明目前北方地区流行的H9N2亚型AIV具有感染哺乳动物的潜在威胁。本研究结果对加强H9N2病毒的分子流行病学监测具有重要意义。

Crosslinking-mediated activation of the FcεRI:Does it need antigen for success?

Mast cells(MCs),hematopoietic cells of the myeloid lineage,are well-known for their pro-inflammatory nature contributing to the development of various allergic and autoimmune diseases.One of the characteristic receptors on MCs,the high-affinity receptor for IgE(FcεRI),is activated in its IgE-bound state via binding and crosslinking by polyvalent antigen.This results in its phosphorylation by the SRC family kinase LYN,initiating differential signaling pathways,eventually triggering immunological effector functions,such as degranulation and cytokine production.Few publications have reported on FcεRI-dependent but antigen-independent MC activation by antibody-mediated crosslinking of membrane molecules(e.g.,transmembrane proteins and glycosphingolipids)that are both localized in membrane rafts and in close vicinity to the FcεRI.In this Viewpoint we will briefly introduce FcεRI-mediated MC stimulation,cite examples of FcεRI-proximal molecules,the crosslinking of which can cause FcεRI-dependent MC activation,and discuss the potential of certain viruses as well as auto-antibodies to act as indirect FcεRI-crosslinking agents.In latter cases,antigen-independent FcεRI-mediated pro-inflammatory MC activation could contribute to the development of detrimental cytokine storms.

Toll样受体与皮肤抗感染免疫

天然免疫分子Toll样受体是一个广泛存在于昆虫、脊椎动物和植物中序列高度保守而古老的家族。它们在天然免疫中可发挥重要的抗感染免疫功能,并与免疫耐受、特异性抗感染免疫,以及一些疾病具有相关性。研究Toll样受体在皮肤组织中识别和抵御常见的几种细菌、病毒及真菌过程中的机制,通过对Toll样受体及其整个系统的认识将为防治各种皮肤感染性疾病开辟广阔前景。

红细胞补体第一受体在乙型慢加急性肝衰竭患者外周血红细胞中的表达动态观察

目的探讨补体第一受体(complement receptor 1,CR1)在乙型慢加急性肝衰竭(hepatitis B virus-acute-on-chronic liver failure,HBV-ACLF)患者外周血红细胞的动态表达变化及其与预后的关系。方法入组2013年12月-2014年6月我院收治的31例HBV-ACLF患者和我科工作人员15例健康对照者(healthy controls,HC),应用流式细胞术检测入组人群外周血红细胞CR1(erythrocyte complement receptor 1,ECR1)的表达量;应用红细胞天然免疫黏附肿瘤细胞的测定方法检测ECR1分子黏附活性:以5个或以上红细胞黏附1个肿瘤细胞为一个结合单位计算黏附率。对HBV-ACLF患者进行为期8周的随访,根据临床疗效分为好转组和无效组,动态观察2组患者外周血红细胞CR1变化。结果 ECR1在健康组(62.30±13.22)的表达明显高于肝衰竭组(41.21±14.33)(t=3.33,P=0.021);8周后慢加急性肝衰竭患者病情好转组(47.31±16.36)较无效组(38.99±10.52)表达高(t=1.95,P=0.049)。健康组黏附活性(66.33±16.79)较慢加急性肝衰竭组(45.55±15.04)高(t=5.01,P=0.000),但8周后不同疗效组之间黏附活性无统计学差异。动态观察结果表明,好转组患者ECR1表达量及黏附活性呈上升趋势,而无效组呈下降趋势或无变化。结论 ECR1表达量及黏附活性与HBV-ACLF患者预后相关,表达增强及黏附活性升高者预后好,动态观察红细胞免疫功能具有重要临床意义。

抗急性出血性结膜炎病毒受体单克隆抗体的制备与鉴定

用细胞保护试验、间接免疫荧光试验及流式细胞仪等方法,对采用细胞融合技术所得到的抗肠道病毒70型(Ev70)和柯萨奇病毒A24型变异株(CA24v)受体的单克隆抗体进行了研究,发现4株抗Hela 细胞膜受体的单克隆抗体能同时阻断Ev70和CA24v 某些毒株感染HeLa 细胞。这一结果提示EV70和CA24存在有相似的受体,对这两种不同的病毒能引起同一种临床疾病的发病机制的阐明有一定的指导意义。

Tim-3 promotes cell aggressiveness and paclitaxel resistance through NF-κB/STAT3 signalling pathway in breast cancer cells

Objective:Although T-cell immunoglobulin and mucin-domain containing molecule-3(Tim-3)has been recognized as a promising target for cancer immunotherapy,its exact role in breast cancer has not been fully elucidated.Methods:Tim-3 gene expression in breast cancer and its prognostic significance were analyzed.Associated mechanisms were then explored in vitro by establishing Tim-3-overexpressing breast cancer cells.Results:In a pooled analysis of The Cancer Genome Atlas(TCGA)database,Tim-3 gene expression levels were significantly higher(P<0.001)in breast cancer tissue,compared with normal tissues.Tim-3 was a prognosis indicator in breast cancer patients[relapse-free survival(RFS),P=0.004;overall survival(OS),P=0.099].Tim-3 overexpression in Tim-3 low breast cancer cells promoted aggressiveness of breast cancer cells,as evidenced by enhanced proliferation,migration,invasion,tight junction deterioration and tumor-associated tubal formation.Tim-3 also enhanced cellular resistance to paclitaxel.Furthermore,Tim-3 exerted its function by activating the NF-κB/STAT3 signalling pathway and by regulating gene expression[cyclin D1(CCND1),C-Myc,matrix metalloproteinase-1(MMP1),TWIST,vascular endothelial growth factor(VEGF)upregulation,concomitant with Ecadherin downregulation).Lastly,Tim-3 downregulated tight junction-associated molecules zona occludens(ZO)-2,ZO-1 and occludin,which may further facilitate tumor progression.Conclusions:Tim-3 plays an oncogenic role in breast cancer and may represent a potential target for antitumor therapy.

DC-SIGN: binding receptors for hepatitis C virus

Objective To review the recent developments in and research into binding receptors of hepatitis C virus (HCV) and especially the role of dendritic cell-specitic adhesion receptor (DC-SIGN) in HCV.Data sources Both Chinese- and English-languge literature was searched using MEDLINE (2000-2003) and the databank of Chinese-language literature (2000-2003).Study selection Relevant articles on DC-SIGN and HCV binding receptors in recent domestic and foreign literature were selected.Data extraction Data were mainly extracted from 40 articles which are listed in the references section of this review. Results DC-SIGN, a dendritic cell-specific adhesion receptor and a type Ⅱ transmembrane mannose-binding C-type lectin, is very important in the function of dendritic cells (DC), both in mediating nave T cell interactions through ICAM-3 and as a rolling receptor that mediates the DC-specific ICAM-2-dependent migration processes. It can be used by HCV and other viral and bacterial pathogens including human immunodeficiency virus (HIV), Ebola virus, CMV and Mycobacterium tuberculosis to facilitate infection. Both DC-SIGN and DC-SIGNR can act either in cis, by concentrating virus on target cells, or in trans, by transmission of bound virus to a target cell expressing appropriate entry receptors. Recent report showed that DC-SIGN not only plays a role in entry into DC, HCV E2 interaction with DC-SIGN might also be detrimental to the interaction of DC with T cells during antigen presentation. Conclusions DC-SIGNs are high-affinity binding receptors for HCV.The clinical strategies that target DC-SIGN may be successful in restricting HCV dissemination and pathogenesis as well as directing the migration of DCs to manipulate appropriate immune responses in autoimmunity and tumorigenic situations.

Toll样受体10作为抗炎模式识别受体在感染性疾病中的作用

Toll样受体10(toll-like receptor 10,TLR10)是由人类TLR10基因编码的一种蛋白质,与TLR1和TLR6的氨基酸的组成高度同源,属于TLR2亚家族。同其他TLR一样,TLR10是参与固有性免疫的一种主要蛋白质分子,也是连接固有性免疫和特异性免疫的重要桥梁。TLR10是一种病原相关分子模式识别受体,可与TLR1或TLR2形成异源二聚体,并在感染性疾病的免疫反应中起重要作用。最新研究证明,TLR10的表达能够抑制TLR2介导的免疫反应,而TLR10的基因变异又可影响其表达水平。现就国内外对TLR10的结构、功能及其基因多态性在感染性疾病中所起的作用的研究作一概述。

Viro-immune therapy:A new strategy for treatment ofpancreatic cancer

Pancreatic ductal adenocarcinoma(PDAC) is an almost uniformly lethal disease with less than 5% survival at five years. This is largely due to metastatic disease, which is already present in the majority of patients when diagnosed. Even when the primary cancer can be removed by radical surgery, local recurrence occurs within one year in 50%-80% of cases. Therefore, it is imperative to develop new approaches for the treatment of advanced cancer and the prevention of recurrence after surgery. Tumour-targeted oncolytic viruses(TOVs) have become an attractive therapeutic agent as TOVs can kill cancer cells through multiple mechanisms of action, especially via virus-induced engagement of the immune response specifically against tumour cells. To attack tumour cells effectively, tumour-specific T cells need to overcome negative regulatory signals that suppress their activation or that induce tolerance programmes such as anergy or exhaustion in the tumour microenvironment. In this regard, the recent breakthrough in immunotherapy achieved with immune checkpoint blockade agents, such as anti-cytotoxic T-lymphocyte-associate protein 4, programmed death 1(PD-1) or PD-L1 antibodies, has demonstrated the possibility of relieving immune suppression in PDAC. Therefore, the combination of oncolytic virotherapy and immune checkpoint blockade agents may synergistically function to enhance the antitumour response, lending the opportunity to be the future for treatment of pancreatic cancer.

Tissue and host tropism of influenza viruses:Importance of quantitative analysis

It is generally accepted that human influenza viruses preferentially bind to cell-surface glycoproteins/ glycolipids containing sialic acids in α2,6-linkage; while avian and equine influenza viruses preferentially bind to those containing sialic acids in α2,3-linkage. Even though this generalized view is accurate for H3 subtype isolates, it may not be accurate and absolute for all subtypes of influenza A viruses and, therefore, needs to be reevaluated carefully and realistically. Some of the studies published in major scientific journals on the subject of tissue tropism of influenza viruses are inconsistent and caused confusion in the scientific community. One of the reasons for the inconsistency is that most studies were quantitative descriptions of sialic acid receptor distributions based on lectin or influenza virus immunohistochemistry results with limited numbers of stained cells. In addition, recent studies indicate that α2,3- and α2,6-linked sialic acids are not the sole receptors determining tissue and host tropism of influenza viruses. In fact, determinants for tissue and host tropism of human, avian and animal influenza viruses are more complex than what has been generally accepted. Other factors, such as glycan topology, concentration of invading viruses, local density of receptors, lipid raft microdomains, coreceptors or sialic acid-independent receptors, may also be important. To more efficiently control the global spread of pandemic influenza such as the current circulating influenza A H1N1, it is crucial to clarify the determinants for tissue and host tropism of influenza viruses through quantitative analysis of experimental results. In this review, I will comment on some conflicting issues related to tissue and host tropism of influenza viruses, discuss the importance of quantitative analysis of lectin and influenza virus immunohistochemistry results and point out directions for future studies in this area, which should lead to a better understanding of tissue and host tropism of influenza viruses.

Features of intestinal T-cell lymphomas in Chinese population without evidence of celiac disease and their close association with Epstein-Barr virus infection

Background Intestinal T-cell lymphoma （ITCL） is a heterogeneous lymphoid neoplastic group with variable clinical and pathological features. ITCL in oriental countries is different from enteropathy-type intestinal T-cell lymphoma （ETCL） in relation to celiac disease and Epstein-Barr virus （EBV）. The objective of this study was to investigate the clinicopathological features, immunophenotype, expression of cytotoxic molecule （TIA-1）, T-cell receptor （TCR）-γ gene rearrangement, and Epstein-Barr virus （EBV） latent infection in primary ITCL without celiac disease in Chinese. Methods The clinical data of 42 patients were analyzed, and the patients were followed up. Compared with human reactive lymphoid tissues, in situ hybridization for EBER1/2, polymerase chain reaction for TCR-~/gene rearrangement, and immunohistochemical staining for immunophenotypes, TIA-1 and EBV latent membrane proteins （LMP-1） were investigated. Survival curves of different clinicopathological features, immunophenotypes, expression of LMPI , TCR-γ/gene rearrangement and therapy were analyzed. Results Three fourths of the patients suffered from ITCL in China were men with a peak age incidence in the 4th decade. Common presenting features included fever and hemotochezia. The prognosis was poor with a median survival of 3.0 months. The lesions were mostly localized in the ileocecum and colon. About 38/42 （90. 5% ） patients demonstrated pleomorphic medium-sized on large seen. All 42 patients with ITCL revealed CD45RO cells. Histological features of celiac disease were rarely positive. Neoplastic cells partially expressed T-cell differentiated antigens （CD3ε, CD4, CD8） and NK cell associated antigen （CD56）. The positive frequency of CD3e, CIM, CD8 and CD56 was 28/42 （66.7%） 7/42 （16.7%）, 10/42 （23.8%） and 12/42 （28.6%） respectively. Thirty-nine cells （92. 9% ） expressed TIA-1, but none expressed CD20 and CD68. More than half of the patients （64. 3% , 64.3% and 59.5% ） revealed TCR-γ primers respectively. EBER1/2 was detected in 41 （97.6%） of LMP-1 was 38. 1% （16/42）. gene rearrangement by three different TCR-γ the 42 patients. The expression frequency ofConclusions Primary ITCL without celiac disease in Chinese is a special highly EBV-associated clinicopathological entity. There are few similarities in patients with celiac disease in western countries. A small proportion of primary ITCLs in Chinese and extranodal NK/T-eell lymphoma of nasal type belong to the same speetrum.

A possible receptor forβ2 glycoprotein I on the membrane of hepatoma cell line smmc7721

Objectives To study the interaction of beta-2-glycoprotein I (β2GP I ) with the membrane of hepatocytes and determine whether β2GP I participates in HBV infection.Methods Ligand blotting, fluorescence microscopy, and fluorescence activated cell sorter (FACS) analysis were used to detect the specific interaction of β2GP I with the hepatoma cell line smmc7721, the gastric carcinoma cell line SGC7901, and the lymphoma cell line HL-60.Results A specific 40 kDa β2GP I band was observed by ligand blotting in the case of smmc7721 cells. No such band was observed in SGC7901 or HL-60 cells. Fluorescence microscopy also revealed specific binding of FITC-β2GP I to smmc7721 cells, but neither to SGC7901 nor HL-60 cells. FACS analysis demonstrated that the binding rate of FITC-β2GP I to smmc7721 cells was significantly higher than these in SGC7901 and HL-60 cells (P<0. 01). The binding rate to smmc7721 cells did not increase with increasing amounts of FITC-β2GP I .Conclusions There is a specificβ2GP I -binding protein on the membrane of hepatoma cells in cell line smmc7721 which as the β2 GP I receptor may participate in HBV infection of hepatocytes.

呼吸道合胞病毒诱导人肺腺癌细胞中TLR3的表达及其在儿童肺炎诊断中的意义

目的研究呼吸道合胞病毒(RSV)诱导人肺腺癌细胞中Toll样受体3(TLR3)的表达及其在儿童肺炎诊断中的意义。方法将A549细胞分成RSV感染组[加入1μg/ml脂多糖(TLR3激动剂)150μl干预后转染RSV病毒]、脂多糖刺激组(加入1μg/ml脂多糖150μl干预)和正常对照组(正常培养),比较不同组别A549细胞肿瘤坏死因子-α、白细胞介素-8、TLR3蛋白和TLR3 mRNA表达。前瞻性选择保定市第二中心医院2019年8月至2021年10月收治的80例RSV感染性肺炎患儿为RSV肺炎组,60例普通肺炎患儿为普通肺炎组,本院体检的60例健康儿童为对照组,比较不同组别血清TLR3 mRNA表达,应用ROC曲线评估血清TLR3对RSV肺炎的诊断效能。结果不同组别A549细胞中TLR3蛋白表达差异有统计学意义(P<0.001)。不同组别A549细胞在不同时点TLR3 mRNA的表达差异均有统计学意义(均P<0.001)。不同组别A549细胞在不同时点肿瘤坏死因子-α和白细胞介素-8的表达差异均有统计学意义(均P<0.05)。三组受试者血清TLR3 mRNA的表达差异有统计学意义(F=155.237,P<0.001)。TLR3 mRNA诊断RSV肺炎的临界值为66.87,其对应的灵敏度为73.75%,特异度为70.83%,曲线下面积(AUC)为0.803(95%CI:0.753~0.855)。结论呼吸道合胞病毒诱导人肺癌细胞,可通过TLR3表达促进疾病发病;血清TLR3可应用于RSV肺炎诊断。

水飞蓟素对呼吸道合胞病毒诱导毛细支气管炎小鼠的保护作用及机制

目的探讨水飞蓟素对呼吸道合胞病毒(RSV)诱导毛细支气管炎小鼠的保护作用及其机制。方法采用鼻腔滴入RSV的方法建立毛细支气管炎小鼠模型,造模成功后随机分成模型组、阳性对照组(利巴韦林,10 mg/kg)、水飞蓟素低剂量组(25 mg/kg)、水飞蓟素中剂量组(50 mg/kg)和水飞蓟素高剂量组(100 mg/kg),另设置对照组,每组12只。测定各组小鼠肺指数及RSV病毒载量;HE染色观察肺组织病理学变化;ELISA检测支气管肺泡灌洗液(BALF)中白细胞介素-4(IL-4)、干扰素-γ(IFN-γ)、转化生长因子-β(TGF-β)、IL-17和IL-10表达水平;流式细胞术检测小鼠外周血中辅助性T细胞17(Th17)和调节性T细胞(Treg)细胞比例;Western blot检测肺组织中Toll样受体4(TLR4)/核因子κB(NF-κB)信号通路相关蛋白TLR4、髓样分化因子88(MyD88)、NF-κB亚基p65亲和肽(NF-κB p65)及核蛋白p-NF-κB p65表达水平。结果与模型组比较,水飞蓟素中、高剂量组小鼠肺损伤及炎症反应均有明显改善,肺指数分别为(1.27±0.17)%、(0.94±0.10)%,RSV病毒载量分别为(2.65±0.19)、(2.13±0.14),外周血中Th17细胞比例分别为(4.47±0.19)%、(3.52±0.13)%,均明显低于模型组(均P<0.05),而外周血中Treg细胞比例分别为(0.88±0.08)%、(1.33±0.12)%,均明显高于模型组(均P<0.05),且BALF中IL-4和IL-17表达水平及肺组织中TLR4/NF-κB信号通路相关蛋白表达水平均明显低于模型组(均P<0.05),BALF中IFN-γ、TGF-β和IL-10表达水平均明显高于模型组(均P<0.05)。结论水飞蓟素调节机体免疫功能、抑制炎症反应,从而改善毛细支气管炎小鼠气道炎症,其机制可能与抑制TLR4/NF-κB信号通路活化相关。