系膜细胞来源的白细胞介素-13对系膜细胞细胞因子基因表达的研究(英文)

目的　白细胞介素 1 3(IL 1 3)是新近发现的一种抗炎性细胞因子 ,其在肾小球肾炎中的作用尚不清楚 ,该研究探讨脂多糖 (LPS)对体外培养的人肾小球系膜细胞 (HMC)表达IL 1 3作用以及IL 1 3对HMC促炎性细胞因子、趋化因子和促纤维化因子基因表达的影响。方法　体外培养HMC ,加入不同浓度的LPS和 (或 )IL 1 3后 ,用逆转录 -聚合酶链反应和ELISA检测HMCIL 1 3mRNA表达和细胞培养上清液中IL 1 3蛋白含量 ;应用核酸酶保护法检测HMC肿瘤坏死因子 α(TNF α)、白介素 - 1α(IL 1α)、白介素 - 1 β(IL 1 β)、单核细胞趋化蛋白 1(MCP 1 )、白介素 8(IL 8)、转化生长因子 - β1 (TGF β1 )mRNA的表达。 结果　未予LPS刺激的HMC不表达IL 1 3mRNA和蛋白 ;LPS呈剂量依赖性和时间依赖性诱导HMC表达IL 1 3mRNA和分泌IL 1 3蛋白。HMC受LPS刺激后 1 2h即可表达IL 1 3mRNA ,4 8h达高峰 ,72h仍维持在较高的水平。HMC受LPS刺激后 2 4h ,其培养上清液中检测到IL 1 3蛋白 ,4 8h和 72h进一步增加。外源性IL 1 3呈剂量依赖性地抑制LPS诱导的系膜细胞TNF α ,IL 1α ,IL 1 β ,MCP 1 ,IL 8,TGF β1mRNA的表达。应用抗IL 1 3抗体中和内源性IL 1 3后 ,上述炎症因子表达增强。结论　IL 1 3是HMC自分泌因子。IL 1 3可抑制LPS诱导     

姜黄素抑制脂多糖刺激的系膜细胞增殖及其白细胞介素1β和巨噬细胞趋化蛋白1基因的表达

目的　观察姜黄素对系膜细胞增殖以及对系膜细胞基质蛋白分泌的影响 ,并进一步探索姜黄素对系膜细胞白细胞介素 (IL 1β)和巨噬细胞趋化蛋白 (MCP 1)基因表达的改变。 方法　采用不同浓度姜黄素处理体外培养的人肾小球系膜细胞后 ,分别收集上清液及细胞 ,应用ELISA的方法测定上清液中胶原Ⅳ和Ⅲ的蛋白分泌量 ,MTT法测定系膜细胞活性 (吸光度值 ) ,RT PCR的方法测定系膜细胞IL 1β和MCP 1基因的相对表达量 ,以未加LPS及姜黄素和仅加LPS不加姜黄素作为对照组。结果　当姜黄素浓度大于或等于 6 2 5 μmol/L时 ,系膜细胞增殖明显受到抑制 (P <0 0 1) ,且表现为浓度依赖性。在基础状态下 ,系膜细胞分泌一定量的胶原Ⅳ和Ⅲ [(10± 9 13)ng/ml和 (2 9 5± 0 5 8)ng/ml],亦有MCP 1mRNA表达 [(42 1± 14 98) % ],但IL 1βmRNA几乎不表达 ;经LPS刺激后其胶原Ⅳ和Ⅲ分泌增加 [(138 75± 2 3 2 3)ng/ml和 (38 2 5± 5 38)ng/ml],同时IL 1β和MCP 1基因表达上调 [分别为 (16 91± 1 6 8) %和 (76 6± 6 5 9) % ],而姜黄素浓度为 4 μmol/L时即能明显抑制LPS刺激的系膜细胞胶原Ⅳ和Ⅲ的蛋白分泌 (P <0 0 5 ) ,且在高浓度时作用更为明显 ;同时姜黄素还能消除LPS上调系膜细胞IL 1β和MCP 1基因表达的作用 (P <     

低分子肝素抑制肾小球系膜细胞增生机制的研究

目的：低分子肝素是肾脏疾病治疗中常用药物,能抑制肾小球系膜细胞的增生,其机制常不清楚,本研究探讨低分子肝素(LMWH)对大鼠肾小球系膜细胞(GMCs)增生水平的影响及其机制。方法：GMCs细胞共设3组:①GMCs组;②LPS组:即GMCs+LPS;③LMWH组:即GMCs+LPS+LMWH,而LMWH终浓度分别为2.5 IU/ml,25 IU/ml和250 IU/ml。采用MTT法于培养24 h和48 h观察各组中GMCs增生水平,选择药物的最佳GMCs增生抑制浓度及时间;采用免疫细胞化学方法观察培养48 h后3组(LMWH终浓度为250 IU/ml)GMCs涂片中单核细胞趋化蛋白-1(MCP-1)及核转录因子-κB(NF-κB)的表达;采用ELISA方法观察培养的上清液中MCP-1浓度。结果：LMWH 250 IU/ml组对GMCs增生的抑制最为显著,其GMCs增生水平低于LPS组和LMWH 2.5 IU/ml,25 IU/ml组(P<0.05);各浓度LMWH对GMCs增生的抑制作用48 h强于24 h(P<0.05)。LMWH 250 IU/ml组48 h的MCP-1阳性率明显低于LPS组(P<0.01),而与GMCs组差异无显著性(P>0.05);LPS组48 h的MCP-1阳性率明显高于GMCs组(P<0.01)。LMWH 250 IU/ml组48 h的NF-κB表达阳性率与LPS组和GMCs组比较差异均无显著性(P>0.05);LPS组的NF-κB表达阳性率明显高于GMCs组(P<0.01)。LMWH 250 IU/ml组GMCs培养上清液中MCP-1浓度明显低于LPS组(P<0.01),与GMCS组差异无显著性(P>0.05)。结论：LMWH能抑制大鼠GMCs增生,明显下调GMCs中MCP-1的异常表达及分泌,而对NF-κB活性无明显抑制。     

银杏叶提取物对大鼠肾小球系膜细胞中细胞外基质及β1整合素表达的影响

目的 观察银杏叶提取物(EGB)对脂多糖(LPS)诱导的大鼠肾小球系膜细胞(GMC)中细胞外基质(ECM)分泌及β1整合素( Itgβ1)表达的影响.方法 体外培养的大鼠GMC鉴定后第3～ 10代用于实验.实验分为5组:对照组,LPS组,EGB高、中、低剂量组.酶联免疫吸附试验法测定6h、12h和24h细胞培养上清液中ECM层黏连蛋白、纤维连接蛋白和Ⅳ型胶原蛋白水平;荧光半定量-PCR法检测Itgβ1mRNA表达的变化.结果 1.正常培养的大鼠GMC可分泌一定量的ECM,LPS组在各时间点分泌ECM均高于对照组(Pa＜0.01),而EGB各剂量组分泌ECM均低于LPS组(Pa＜0.01);2.正常培养的大鼠GMC可表达一定量Itgβ1mRNA,LPS组各时间点Itgβ1mRNA表达量均高于对照组(Pa＜0.01),EGB各剂量组Itgβ1mRNA表达量均低于LPS组(Pa＜0.01).结论 LPS可诱导GMCItgβ1mRNA表达及ECM分泌增加,EGB可抑制LPS诱导的GMC Itgβ1 mRNA表达及ECM分泌增加,EGB可通过抑制细胞因子及ECM分泌等分子生物学机制对肾脏起保护作用.     

福辛普利对大鼠肾小球系膜细胞转化生长因子-β1蛋白及其mRNA表达的影响

目的观察血管紧张素酶抑制剂（ACEI）-福辛普利（FOS）对脂多糖（LPS）诱导大鼠肾小球系膜细胞（GMC）转化生长因子-β（TGF-β1）蛋白及mRNA表达的影响，探讨FOS延缓肾小球硬化机制。方法按经典方法体外培养大鼠GMC，转种培养后分为对照组、LPS组、LPS＋FOS组。采用ELISA法测定GMC培养上清6、12、24hTGF-β1蛋白水平，荧光半定量RT-PCR法检测TGF-β1mRNA表达。结果LPS诱导组GMC分泌TGF-β1蛋白及mRNA表达均高于对照组，LPS＋FOS组GMC分泌TGF-β1及mRNA表达较LPS组明显下降。结论FOS从蛋白和mRNA两个水平均对体外培养大鼠GMC产生TGF-β1有明显抑制作用，提示FOS抑制GMC产生TGF-β1可能是延缓肾小球硬化的重要作用机制之一。     

福辛普利对大鼠肾小球系膜细胞β1整合素表达及细胞外基质分泌的影响

目的观察福辛普利(fosinopril,FOS)对脂多糖(LPS)诱导的大鼠肾小球系膜细胞(GMC)β1整合素表达及分泌细胞外基质(ECM)的影响。方法大鼠GMC原代体外培养,鉴定3～10代后用于实验。实验分为5组:对照组、LPS刺激组(LPS)、FOS高、中、低剂量组(分别为FOS1组、FOS2组、FOS3组)。酶联免疫吸附试验(ELISA)测定6、12和24 h细胞培养上清液中ECM层黏连蛋白(LN),纤维连接蛋白(FN)和Ⅳ型胶原蛋白(ColⅣ)含量;荧光半定量RT-PCR检测β1整合素mRNA表达。结果体外培养的大鼠GMC可分泌一定量的ECM,在各时间点,LPS组GMC的ECM分泌均高于对照组(P<0.01),而FOS各组GMC的ECM分泌均低于LPS组(P<0.01);体外培养的大鼠GMC可表达一定量的β1整合素mRNA,在各时间点,LPS组GMC的β1整合素mRNA表达量均高于对照组,FOS各组GMC的β1整合素mRNA表达量均低于LPS组。结论 LPS可诱导大鼠GMCβ1整合素表达及ECM分泌增加,而FOS可抑制LPS诱导的大鼠GMCβ1整合素表达及ECM分泌增加,FOS可以通过抑制细胞因子及ECM分泌等非血流动力学机制对肾脏起保护作用。     

维生素E对肾小球系膜细胞一氧化氮分泌及单核细胞趋化蛋白-1表达的影响

目的　研究维生素E(VitE)对大鼠肾小球系膜细胞 (GMCs)单核细胞趋化蛋白 1(MCP 1)、一氧化氮 (NO)表达的影响。方法　将研究大鼠分对照组、脂多糖 (LPS)组、5 0mg/LVitE LPS组、10 0mg/LVitE LPS组、2 0 0mg/LVitE LPS组共 5组培养肾小球系膜细胞 ,分 2 4、4 8、72h 3个时间段收集培养上清及培养细胞 ;实验末应用生化法测定培养上清NO水平 ,应用ELISA技术检测培养上清MCP 1水平 ,应用RT PCR检测MCP 1mRNA表达。结果　 2 4h末LPS组GMCsNO分泌均较对照组降低 (P <0 .0 1) ,其他各组GMCsNO分泌均较对照组增高 (P均 <0 .0 1) ,MCP 1分泌与表达均较对照组增高 (P均 <0 .0 1) ;4 8h末各组NO分泌均较对照组降低 ,LPS组在 4 8h末与 72h末MCP 1分泌较其他各组明显增高 (P均 <0 .0 1) ;与LPS组相比 ,4 8h末与 72h末不同浓度VitE组MCP 1分泌降低 ,与对照组比较各组在不同时间段MCP 1mRNA表达明显增高 (P均 <0 .0 1) ,MCP 1mRNA表达在 4 8、72h较LPS组明显降低 (P均 <0 .0 1) ,且发现各组MCP 1mRNA表达在4 8、72h无明显差异 ,10 0mg/LVitE组与 2 0 0mg/LVitE组较 5 0mg/LVitE组MCP 1mRNA表达明显降低 (P均 <0 .0 1) ,但两组间无明显差异 ,经相关分析表明 ,NO分泌与MCP 1分泌与表达明显负相关 (γ =0 .6 13、0 .6     

苦参碱对脂多糖诱导人胚肾小球系膜细胞STAT1、3及CTGF、PDGF表达的影响

目的观察苦参碱(Ma)对脂多糖(LPS)诱导的肾小球系膜细胞(MC)中信号转导子与转录激活子(STAT)分子1、3,结缔组织生长因子(CTGF)及血小板源性生长因子(PDGF)表达的影响,探讨苦参碱抑制增殖的机制。方法原代培养人胚肾小球系膜细胞并鉴定。实验分为正常对照组、脂多糖(10μg/ml)组、脂多糖(10μg/ml)+苦参碱(320μg/ml)组,分别于12、24、48h采用Real-TimePCR检测STAT1、3、CTGF及PDGF mRNA表达及Western blot检测p-STAT1、3蛋白表达。结果与正常对照组相比,在12、24、48h时间段,10μg/ml的LPS能够促进人肾小球系膜细胞增殖,320μg/ml的Ma对MC均有抑制增殖作用(P<0.01);在12、24、48h,LPS组STAT1、3、CTGF及PDGF mRNA增高,苦参碱处理组较LPS组表达明显降低,且在24、48h抑制明显(P<0.01);LPS组P-STAT1在12、24、48h蛋白表达均上调,p-STAT3在24、48h蛋白表达明显上调(P<0.01),与LPS组相比,苦参碱处理组p-STAT1、3蛋白表达均下调,但...     

福辛普利对大鼠肾小球系膜细胞增殖及分泌细胞外基质的影响

目的观察福辛普利（FOS）对脂多糖（LPS）诱导的大鼠肾小球系膜细胞（GMC）增殖及分泌细胞外基质（ECM）的影响。方法建立体外培养的大鼠GMC,鉴定后3—10代用于实验。实验分为五组：对照组、LPS刺激组（LPS组）、福辛普利（FOS）高、中、低剂量组（分别为FOS1组、FOS2组、FOS3组）。甲基噻唑基四唑（MTT）比色法测定24h和48h两个时间点各组细胞增殖,酶联免疫吸附试验（ELISA）测定6h、12h和24h细胞培养上清液中ECM蛋白含量;荧光半定量RT-PCR法检测ECM纤维连接蛋白（LN）β2mRNA表达的变化。结果（1）LPS可诱导GMC增殖,FOS可抑制LPS诱导的GMC增殖;（2）正常培养的大鼠GMC可分泌一定量的ECM,LPS组在各时间点分泌ECM均高于对照组（P〈0．01）,而FOS各组分泌ECM均低于LPS组（P〈0．01）;（3）正常培养的大鼠GMC可表达一定量LNβ2 mRNA,LPS组在各时间点LNβ2mRNA表达量均高于对照组,FOS各组表达量均低于LPS组。结论LPS可诱导GMC增殖且分泌ECM增加,FOS可抑制LPS诱导的GMC增殖,从蛋白和mRNA两个水平抑制LPS诱导的GMC分泌ECM增加,为FOS对肾脏的保护作用提供了理论依据。     

15-甲基-脂氧素A_4对大鼠系膜增殖性肾炎干预作用的研究

目的：已发现脂氧素A4(LXA4)可抑制肾小球系膜细胞的体外增殖,该研究旨在了解LXA4同系物15-甲基-LXA4是否抑制大鼠系膜增殖性肾炎的病理进展,并探讨其作用的信号转导分子机制。方法：使用小鼠抗大鼠Thy1.1单克隆抗体静脉内1次性注射制备大鼠系膜增殖性肾炎。使用15-甲基-LXA4静脉内注射干预大鼠系膜增殖性肾炎。检测尿蛋白、肾小球白细胞浸润、系膜细胞增生评分、增殖性细胞核抗原(PCNA)表达。应用RT-PCR方法检测肾小球白介素(IL)-1β,IL-6的mRNA表达,应用放免法测定肾小球IL-1β,IL-6水平。应用West-ernBlot测定肾小球磷酸化的磷脂酰肌醇-3-激酶(PI3-K)、Akt1与p27kip1表达,应用凝胶电泳迁移率试验(EMSA)测定肾小球核因子-κB(NF-κB)及信号转导及转录活化子-3(STAT3)活性。结果：大鼠系膜增殖性肾炎发病后第1~4天,肾小球白细胞计数、IL-1β、IL-6的mRNA与蛋白表达、NF-κB活性升高;第4天尿蛋白、肾小球系膜细胞增生评分、PCNA表达、肾小球PI3-K、Akt1与STAT3活性升高,p27kip1表达减低。应用15-甲基-LXA4干预,可减少肾炎大鼠尿蛋白、肾小球白细胞计数、系膜细胞增生评分、PCNA表达、IL-1β、IL-6的mRNA与蛋白表达(均P<0.05),减低PI3-K、Akt1、NF-κB、STAT3活性,阻止p27kip1表达减低。结论：15-甲基-LXA4可有效地抑制大鼠系膜增殖性肾炎的尿蛋白、肾小球炎性反应,系膜细胞增殖,其机制与抑制PI3-K/Akt1/p27kip1/cyclin途径、STAT3、NF-κB活性有关。     

Enhanced expression of cytokines/chemokines in cerebrospinal fluids in mumps meningitis in children

Background: The mumps virus is frequently the causative agent in aseptic meningitis and mumps has still prevailed in Japan. We compared data obtained from patients with mumps meningitis and patients with aseptic meningitis caused by other viruses in order to identify mumps meningitis‐specific cytokine/chemokine alterations in cerebrospinal fluide (CSF). Methods: We elucidated the cytokine/chemokine network based on the cytokine/chemokine profiles in CSF from children with mumps meningitis and meningitis due to other viral infections using multiplex cytokine measurement. Seventeen cytokines/chemokines, namely interleukin (IL)‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐7, IL‐8, IL‐10, IL‐12 (p70), IL‐13, IL‐17, interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α, granulocyte colony‐stimulating factor (G‐CSF), granulocyte monocyte colony‐stimulating factor (GM‐CSF), monocyte chemoattractant protein‐1 (MCP‐1) and macrophage inflammatory protein‐1β (MIP‐1β), were measured simultaneously in CSF supernatants from eight children with mumps meningitis, 11 children with other types of viral meningitis and eight children with fever without neurological complications such as convulsion. Results: We found that IL‐8, IL‐10, IL‐12, IL‐13 and IFN‐γ showed a statistically significant increase in CSF from mumps meningitis when compared to other types of viral meningitis and fever without neurological complications. Conclusion: Mumps meningitis may induce a distinct immunological response when compared with other types of viral meningitis.     

Increased TLR2 expression in patients with type 1 diabetes: evidenced risk of microalbuminuria

Ururahy MAG, Loureiro MB, Freire‐Neto FP, Souza KSC, Zuhl I, Brandão‐Neto J, Hirata RDC, Doi SQ, Arrais RF, Hirata MH, Almeida MG, Rezende AA. Increased TLR2 expression in patients with type 1 diabetes: evidenced risk of microalbuminuria. Objective: To study the activation of an inflammatory cascade through leukocyte mRNA expression of TLR2, TLR4, MyD88, and pro‐inflammatory cytokines in individuals with childhood onset type 1 diabetes. Design and methods: Seventy‐six type 1 diabetic patients and 100 normoglycemic subjects (NG) 6 to 20 years old were recruited. Type 1 diabetic patients (DM1) were considered to have good (DM1G) or poor (DM1P) glycemic control according to the values of glycated hemoglobin. TLR2, TLR4, MyD88, interleukin ‐1β (IL‐1β), IL‐6, and tumor necrosis factor alpha (TNF‐α) mRNA expressions were measured in peripheral blood leukocytes (PBL) by real‐time polymerase chain reaction (PCR). Urea, creatinine, albumin, and total protein serum levels were determined. Urinary albumin‐to‐creatinine ratio (ACR) was calculated. Results: DM1 and DM1P patients showed higher glycated hemoglobin (10 and 11%, respectively) and serum glucose concentrations (208 and 226 mg/dL, respectively) compared to NG (Glycated hemoglobin: 7% and glucose: 76 mg/dL) (p < 0.05). PBL mRNA expressions of TLR2, MyD88, IL‐1β, IL‐6, and TNF‐α were higher in DM1 and TLR2, IL‐1β, and IL‐6 expressions were higher in DMP1 compared to NG (p < 0.05). In DM1, serum albumin and total protein were lower, while serum urea and ACR were higher in comparison to NG (p < 0.05). However, these differences compared to NG were more pronounced in DM1P, which included nine individuals with microalbuminuria. Conclusions: Increased mRNA expression of TLR2, MyD88, and pro‐inflammatory cytokines in leukocytes of patients with childhood onset type 1 diabetes indicates the development of a TLR2‐mediated pro‐inflammatory process, which may also be associated with an early inflammatory process in the kidney and the occurrence of microalbuminuria.     

Different cytokine signatures in children with localized and invasive adenovirus infection after stem cell transplantation

Haveman LM, de Jager W, van Loon AM, Claas ECJ, Prakken BJ, Bierings M. Different cytokine signatures in children with localized and invasive adenovirus infection after stem cell transplantation. Pediatr Transplantation 2010: 14:520–528. © 2010 John Wiley & Sons A/S. Abstract HAdV infection is a dangerous complication after pediatric SCT. In this study, we aimed at determining the cytokine profile in plasma samples in case of HAdV infection after SCT to gain more knowledge about the HAdV‐specific immune response. In this prospective study, 47 pediatric SCT recipients were included in three yr. By using particle‐based MIA, 17 different cytokines were analyzed in 41 plasma samples of patients with a localized HAdV infection (presence of HAdV in feces, urine or throat detected by culture) and patients with invasive HAdV infection (HAdV viremia in blood, detected by PCR). In patients with invasive HAdV infection, but not in patients with localized HAdV infection, the pro‐inflammatory cytokines IL1β, IL6, IL8, IL12, IFNγ, TNFα, and also IL17, MIP1α, OSM, and IP10 were produced. The simultaneous release of the cytokines IL1β, IL17, IL18, OSM, MIP1α, and IP10 was related to invasive HAdV infections. We also show that cytokine signatures can be helpful to differentiate invasive HAdV infection from GvHD and EBV infections. In conclusion, after SCT, children with invasive HAdV infection have a different cytokine profile compared with patients with a localized HAdV infection.     

CMV和HCV肝炎婴儿血清IFN-α,IL-8,TNF-α和NO的水平变化

目的　了解巨细胞病毒肝炎 (CMV IgM抗体阳性 )和丙型肝炎 (HCV IgM抗体阳性 ) 1～ 6月的婴儿患者血清中某些炎性介质的异常变化。方法　应用ELISA法和硝酸还原酶法 ,分别检测了 5 6例CMV抗体和6 7例HCV抗体阳性婴儿肝炎综合征 (婴肝 )患儿及正常对照组 5 8例小儿的血清干扰素α (IFN α) ,白细胞介素 8(IL 8) ,肿瘤坏死因子 α (TNF α)和一氧化氮 (NO)的含量。结果　正常对照组 5 8例血清IFN α ,IL 8,TNF α ,NO含量分别为 2 2 6 .74± 73.82ng/L ,13.2 4± 5 .36ng/L ,2 17.14± 76 .30ng/L ,2 5 .98± 8.70 μmol/L。CMV抗体阳性婴肝组血清IFN α ,IL 8,TNF α和NO的含量分别为 5 82 .2 6± 131.72ng/L ,75 .2 8± 33.5 7ng/L ,42 9.46± 15 6 .32ng/L和5 9.87± 16 .42 μmol/L ,明显高于正常对照组 (P <0 .0 1) ;HCV抗体阳性婴肝组上述四项指标含量分别为5 5 8.32± 114.6 4ng/L ,71.34± 2 7.6 4ng/L ,374.35± 138.4ng/L和 6 2 .2 4± 2 1.38μmol/L ,其含量亦明显高于正常对照组 (P <0 .0 0 1)。CMV与HCV抗体阳性婴肝组比较 ,无明显差异 (P >0 .0 5 )。TNF α和NO在这两组婴肝中分别呈正相关 (r1=0 .6 2 ,r2 =0 .5 7,P<0 .0 1)。结论　CMV和HCV抗体阳性婴肝急性期患儿 ,血清TNF α,IL 8,IFN     

中枢神经系统疾病合并全身炎症反应综合征患儿血清TNF-αIL-1βIL-6的动态变化及意义

目的：探讨细胞因子在中枢神经系统疾病合并全身炎症反应综合征(SIRS)及多器官功能障碍综合征(MODS)发生发展中的意义及其与SIRS/MODS严重程度的相关性，以初步探讨SIRS及MODS的发生机制，为临床防治提供理论依据。方法：选择该院PICU神经系统疾病患儿26例，用IMMULITE化学发光免疫分析仪测定入院第1，3，5天TNF-α，IL-1β，IL-6的含量。结果：第1，3，5天TNF-α，IL-1β，IL-6含量在SIRS组、MODS组及死亡组均较非SIRS组、非MODS组及非死亡组明显升高(P<0.05)。且死亡组上述各项指标均持续维持在较高水平。结论：TNF-α，IL-1β，IL-6的含量可反映病情严重程度，为探讨细胞因子在SIRS/MODS发病机制中的作用提供了依据，指导临床早期诊断、治疗。     

肠外营养导致大鼠肝细胞炎症因子及受体基因表达的变化及临床意义

目的 长期应用全胃肠外营养(total patenterl nutrition,TPN)相关肝胆功能损害的发病机制仍不清楚.本研究旨在观察不同营养途径下,大鼠肝脏炎症因子及其受体基因表达的差异,以进一步探讨炎症细胞因子及其受体在TPN相关肝损伤中的作用及町能机制.方法 选择12只雄性SD大鼠,随机分为TPN组(6只)和...     

High tissue factor in lungs and plasma associates with respiratory morbidity in preterm infants

Aim: In preterm infants, inflammation and intra‐alveolar fibrin formation characterize respiratory distress syndrome (RDS). Tissue factor (TF) is a link between inflammation and coagulation pathways. We investigated the relationship between TF and cytokines in preterm infants to gain information of the role of TF in the inflammatory response. Methods: We measured TF in plasma and in tracheal aspirates and analysed TF on monocytes by flow cytometry and 13 cytokines from plasma, in 56 preterm infants (birthweight 600–1500 g) during their first week. Results: Plasma TF increased and peaked on day 3 and correlated with both RDS and inversely with paO2/FIO2. On day 1, TF in tracheal aspirates was 10‐fold higher than in plasma and correlated with plasma TF (4888 vs. 506 pg/mL, R = 0.692, p = 0.013, n = 12). Of main pro‐inflammatory cytokines, plasma TF correlated post‐natally with IL‐8 and IL‐6 but not with IL‐1 or TNF‐α. Conclusions: Respiratory morbidity associates with high TF in lungs and plasma. In sick newborn infants, upregulation of TF may be mediated by IL‐6 and IL‐8. High TF and pro‐inflammatory cytokines may together participate in the pathogenesis of pulmonary and extrapulmonary injury in preterm infants through pro‐inflammatory mechanisms.     

Expression of angiogenesis-related factors and inflammatory cytokines in placenta and umbilical vessels in pregnancies with preeclampsia and chorioamnionitis/funisitis

We hypothesized that gene expression in placenta and umbilical vessels are affected by intrauterine environment and some of the expression in umbilical vessels originating from the fetus could reflect fetal condition of these complicated pregnancies. Expression of angiogenesis‐related factors and inflammatory cytokines were examined in placenta and umbilical vessels to clarify the effects of intrauterine environment of pregnancies complicated by preeclampsia and chorioamnionitis/funisitis. Forty‐six preterm cesarean section deliveries were classified into three groups based on maternal condition during prenatal monitoring: preeclampsia (PE) (n = 11), chorioamnionitis/funisitis (CAM) (n = 8), and preterm control (PC) (n = 27). Angiogenesis‐related factors and inflammatory cytokines in placentas, umbilical arteries and umbilical veins were analyzed by RT‐PCR and immunohistochemistry. We demonstrated that Ang‐2, Tie‐2, and Dll4 increase in the placentas of PE compared to PC for the first time, and we confirmed the findings of previous reports showing the high expression of HIF‐1α, sFlt‐1, endoglin, leptin, and AT1R. Expression of angiogenesis‐related factors, including HIF‐1α, VEGF, angiopoietin, and TGF‐β systems, and inflammatory cytokines, such as TNF‐α and IL‐6, increased in umbilical vessels of PE. Umbilical veins of CAM showed a higher Dll4 level than did PC. In preeclampsia, abnormal expressions of angiogenesis‐related factors related to lifestyle diseases in adulthood were seen in the placenta and umbilical vessels as compared to PC. Chorioamnionitis/funisitis showed only upregulation of DII4 in umbilical veins.     

Cytokines in acute rheumatic fever

Plasma concentrations of inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-8 and TNFα) were determined by ELISA in 27 patients with acute rheumatic fever (RF), 12 with only arthritis (RFA) and 15 with rheumatic heart disease (RHD), before, during and after treatment. Altogether, significant increases in TNFα, IL-8 and IL-6 levels were observed in the acute phase as compared to the data found during and after treatment. No significant differences were observed for the other cytokines. Elevations of one or more of the inflammatory cytokines were observed in 9 of 12 patients with RFA, and 12 of 15 with RHD. Increase of TNFα (6/9) and IL-8 (5/9) levels were higher in RHD patients with cardiac failure. These cytokines were below the detection limits on day 7 of treatment in all 22 patients, except in two, and in all 10 days after treatment. Conclusions?These findings suggest that inflammatory cytokines, as TNFα, IL-8 and IL-6, may play a patho‐genic role in rheumatic fever.