血必净对百草枯中毒老年大鼠肺纤维化的干预作用

目的 探讨血必净对百草枯中毒老年大鼠肺纤维化的干预作用及机制.方法 老年SD雄性大鼠72只分为对照组、百草枯组和血必净组.对HE病理结果进行计算机灰度扫描半定量分析,用RNA酶保护实验的方法检测IL-10/γ干扰素(IL-10/IFN-γ)mRNA的表达.结果 百草枯组与对照组相比,对照组的Th1优势转为百草枯组的Th2优势,于第5天达高峰.血必净组可以显著抑制IL-10 mRNA的表达,但对IFN-γ影响不大,可以逆转为Th1优势.结论 血必净可将百草枯致大鼠肺损伤模型中以IL-10升高为主的Th2优势逆转为IFN-γ为主的Th1优势,通过抗炎和免疫调节作用减轻肺组织炎症损伤和肺纤维化程度.     

Th1/Th2细胞因子的平衡与实验性肺间质纤维化

目的观察核因子-κB（NF-κB）及Th1/Th2细胞因子在博莱霉素所致小鼠肺纤维化模型中的表达及作用。方法气管内滴入博莱霉素建立小鼠肺纤维化模型,给予P65的反义寡核苷酸作为干预因素,应用双抗夹心ELISA法对Th1/Th2细胞因子的代表因子IFN-γ和IL-4分别进行检测,以IFN-γ/IL-4代表Th1/Th2细胞因子的比值。应用免疫组化方法检测肺组织中NF-κB的活性。并分别测定不同时间段肺泡灌洗液中羟脯氨酸的含量。结果肺纤维化的动物模型中NF-κB活性明显增强;出现Th1/Th2细胞因子失衡;P65反义寡核苷酸明显抑制NF-κB活化,并明显纠正Th1/Th2细胞因子失衡,减轻肺泡炎和肺纤维化程度。结论 NF-κB的活化可能为肺间质纤维化的始动因子,阻断其活性可以纠正Th1/Th2的失衡情况,明显改善肺纤维化的病理过程。     

白细胞介素13在博莱霉素致肺纤维化大鼠肺组织的表达及其意义

目前研究表明，细胞因子网络在肺纤维化发病过程中发挥重要作用，肺纤维化时细胞因子平衡向Th2方向转化。白细胞介素13（IL-13），是一种主要由Th2细胞分泌的细胞因子，与肺纤维化关系密切。我们采用博莱霉素（BLM）致大鼠肺纤维化模型，探讨IL-13在炎症反应至肺纤维化的各个阶段所发挥的生物学效应及病理机制。     

三氧化二砷对博莱霉素致大鼠肺纤维化的影响及其作用机制

肺泡炎是肺纤维化疾病的发病机制之一，有研究发现诱导肺内炎性细胞凋亡可以减轻博莱霉素A5（BLM-A5）所致大鼠肺泡炎和肺纤维化程度。三氧化二砷（As2O3）可以诱导多系统的多种细胞发生凋亡，但As2O3对肺纤维化疾病是否有作用，目前尚未见报道。本实验目的是探索适当剂量的As2O3能否诱导肺纤维化大鼠支气管肺泡灌洗液（BALF）中的炎性细胞发生凋亡，从而减轻肺泡炎和肺纤维化。     

白细胞介素12对博莱霉素致大鼠肺纤维化的治疗作用

特发性肺纤维化（IPF）是一种原因不明、主要以普通型间质性肺炎为病理表现，进展性肺纤维化为特征的肺疾病。研究表明肺纤维化形成与Th1和Th2因子间的失衡有一定关系。我们通过对各组大鼠肺组织病理变化、羟脯氨酸（Hyp）含量、肺系数、支气管肺泡灌洗液（BALF）中γ干扰素（INF-γ）、白细胞介素4（IL-4）的含量的比较，观察Th1／Th2细胞因子在肺纤维化形成过程中的变化，探讨白细胞介素12（IL-12）是否具有调节Th1／Th2细胞因子失衡从而达到抗纤维化的作用。     

静脉注射不同剂量博莱霉素诱导小鼠肺纤维化的比较研究

目的寻求建立小鼠肺纤维化模型的改良方案。方法雄性C57BL/6小鼠随机分为单次和多次注射模型组。单次注射模型组分为博莱霉素100、150、200 mg/kg组及对照组1;多次注射模型组分为博莱霉素50 mg/kg组及对照组2。取小鼠肺组织行病理检查,免疫组化检测肺Ⅰ型胶原蛋白、TGF-β1和α-SMA的表达。结果在单次注射模型组中,100、150、200 mg/kg组的肺泡炎均于第2周达峰(P0.01);肺纤维化分别在第2、4、4周达峰(P0.01)。在多次注射模型组中,50 mg/kg组肺泡炎和肺纤维化均在第10周达峰(P0.05)。TGF-β1和α-SMA在肺泡炎和纤维化部位表达明显增加。结论尾静脉单次注射博莱霉素200mg/kg可有效诱导肺纤维化,复制一个相对稳定的肺纤维化模型。     

雷帕霉素对大鼠肺纤维化模型的干预作用及对转化生长因子表达的影响

目的研究雷帕霉素对大鼠肺纤维化模型的干预作用及可能的机制。方法150只SD大鼠采用随机数字表随机分成3组,每组50只：①雷帕霉素组。经气管内灌注博莱霉素诱导肺纤维化,随后每日用雷帕霉素口服溶液0．5mg／kg灌胃进行干预;②模型组,气管内灌注用博莱霉素,灌胃用生理盐水;③对照组,气管内灌注和灌胃均用生理盐水。各组动物均于气管内灌药后第3、7、14、28、56天分别处死10只。通过HE染色、Masson胶原染色、天狼猩红染色偏光法及测定肺组织羟脯氨酸浓度来观察肺泡炎和肺纤维化的程度。用逆转录-聚合酶链反应检测肺组织转化生长因子β1（TGF-β1）的mRNA表达。用免疫组化法检测大鼠肺组织TGF-β1蛋白的表达。结果模型组的肺组织羟脯氨酸含量和肺泡炎程度在各时间点均高于对照组,模型组的肺纤维化程度在第14、28和56天高于对照组（P〈0．05）;雷帕霉素组肺组织羟脯氨酸含量在第14、28和56天低于模型组,雷帕霉素组在第14和28天肺泡炎的程度低于模型组,雷帕霉素组在第28和56天肺纤维化程度低于模型组（P〈0．05）;模型组TGF-β1的mRNA表达在第3、7、14和28天高于对照组,雷帕霉素组TGF-β1的mRNA表达在第7和14天低于模型组（P〈0．05）。结论雷帕霉素能减轻博莱霉素诱导的大鼠肺纤维化,这种作用有可能部分通过抑制TGF-β1的表达而实现。     

姜黄素干预对博莱霉素诱导的大鼠肺纤维化的影响

目的利用博莱霉素诱导的大鼠肺纤维化模型观察姜黄素对肺纤维化的作用效果及其机制。方法54只大鼠按随机数字表法分为正常对照组、博莱霉素组和姜黄素组，每组18只。正常对照组：于实验0d气管内一次性注入生理盐水2ml／kg，第14天起每日腹腔注射生理盐水0．5ml／kg；博莱霉素组：气管内一次性注入博莱霉素屯制剂5mg／kg，第14天起每日腹腔注射6％乙醇和6％聚乙二醇混合溶液0．5ml／ks；姜黄素组：气管内一次性注入博莱霉素屯制剂5mg／kg，第14天起每日腹腔注射姜黄素（溶于6％乙醇和6％聚乙二醇混合溶液）50mg／kg。分别于第17、21、28天各取6只大鼠处死，取肺组织行苏木精-伊红（HE）和Masson染色以观察其病理变化；用逆转录-聚合酶链反应（RT-PCR）法测定肺组织中转化生长因子β1（TGF-β1）和干扰素γ（IFN-γ）mRNA表达；用消化法测定羟脯氨酸含量，收集支气管肺泡灌洗液（SALF）测定TGF-β1、IFN-γ的含量。结果（1）肺泡炎评分：姜黄素组与博莱霉素组在第28天分别为（1．3±0．5）分、（2．0±0．9）分，两组比较差异有统计学意义（q=3．26，P〈0．05）；（2）肺纤维化评分：姜黄素组与博莱霉素组在第21天分别为（1．3±0．5）分、（1．8±0．4）分，第28天分别为（1．2±0．4）分、（2．2±1．O）分，两组比较差异有统计学意义（q值分别为3．33、4．00，P均〈0.05）；（3）肺组织羟脯氨酸含量：姜黄素组与博莱霉素组在第28天分别为（1．75±0．36）μg／g、（2．47±0．24）μg／g，两组比较差异有统计学意义（q=7．20，P〈0．01）；（4）BALF中TGF-β1含量：姜黄素组与博莱霉素组在第21天分别为（20±3）ng／L、（39±7）ng／L，第28天分别为（24±4）ng／L、（40±7）ng／L，两组比较差异有统计学意义（q值分别为5．30、6．27，P均〈0．05）；（5）肺组织中TGF-β1mRNA的表达：姜黄素组与博莱霉素组在第21天分别为0．51±0．11、0．59±0．13，第28天分别为0．50±0．07、0．64±0．11，两组比较差异无统计学意义（q值分别为1．55、3．13，P均〉0．05）；（6）BALF中IFN-γ含量：姜黄素组与博莱霉素组在第21天分别为（28±5）ng／L、（35±13）ng／L，第28天分别为（30±11）ng／L、（39±13）ng／L，两组比较差异无统计学意义（q值分别为1．85、2．03，P均〉0．05）；（7）肺组织中IFN-γmRNA的表达：姜黄素组与博莱霉素组在第21天分别为0．49±0．17、0．50±0．08，第28天分别为0．52±0．15、0．52±0．11，两组比较差异无统计学意义（q值分别为0．17、0．00，P均〉0.05）。结论姜黄素可减轻博莱霉素诱导的大鼠肺泡炎和肺纤维化，其作用机制可能与抑制TGF-β1有关。     

肺间质纤维化小鼠肺内T细胞γ-干扰素和转化生长因子β1的表达

目的 探讨肺组织内T细胞及其转化生长因子β1(TGF-β1)/γ-干扰素(IFN-γ)表达与肺间质纤维化的关系.方法 C57BL/6小鼠30只,随机分为5组,即正常对照组和博莱霉素1、2、3、4周组.采用气管内注射博莱霉素(5 mg/kg)建立纤维化模型,分别于造模后1、2、3、4周断头处死,留取各组小鼠肺组织,观察肺泡炎和肺纤维化程度,流式细胞仪在单个细胞水平检测CD4+、CD8+、CD3+/CD8-/IFN-γ+和CD3+/CD8-/TGF-β1+细胞的频率.结果 博莱霉素组小鼠出现明显纤维化;与正常对照组相比,博莱霉素组肺组织CD4+明显增多,CD8+显著降低(P值均<0.01);博莱霉素组肺组织CD4+T细胞来源IFN-γ水平低于正常对照组,而CD4+T细胞来源TGF-β1水平显著增高于正常对照组(P值均<0.01);CD4+TGF-β1+/CD4+IFN-γ+比值进行性增高,与肺纤维化评分呈正相关(r=0.683,P<0.01).结论 CD4+T细胞来源IFN-γ与TGF-β1分别下调与上调,参与肺纤维化.     

阿奇霉素对弓形虫病大鼠血清细胞因子水平影响的实验研究

目的检测阿奇霉素治疗对弓形虫病大鼠血清IFN-γ、IL-4、TNF-α等细胞因子水平的影响。方法将30只SD大鼠随机分成3组:阿奇霉素治疗组、感染对照组和正常对照组。腹腔注射2×105个/ml活的纯化弓形虫速殖子悬液(CF-11纤维素纯化)2ml于SD大鼠,建立大鼠弓形虫病模型,用阿奇霉素200mg/(kg·d)连喂7d。9周后取大鼠血清,应用ELISA方法检测外周血IFN-γ、TNF-α、IL-4等细胞因子水平。结果弓形虫感染组大鼠血清IFN-γ、TNF-α、IL-4等细胞因子水平均显著高于阿奇霉素治疗组和正常对照组大鼠血清相对应的细胞因子水平(P均<0.05)。结论弓形虫感染可引起大鼠血清IFN-γ、IL-4、TNF-α等细胞因子水平升高。阿奇霉素可有效治疗弓形虫感染对大鼠的损害。     

呼吸道合胞病毒对致敏小鼠T辅助细胞相关细胞因子表达的作用

目的　探讨经卵白蛋白 (OVA)雾化致敏的小鼠受呼吸道合胞病毒 (RSV)感染后肺内炎症发展的特点及与T辅助细胞有关的细胞因子的反应。方法　 40只小鼠随机分成 4组 ,每组 1 0只。对照组 :磷酸盐缓冲液 (PBS)雾化 1 0天 ,HEP 2细胞液滴鼻 ;RSV组 :PBS液雾化 ,RSV滴鼻 ;OVA组 :OVA致敏 ,HEP 2细胞液滴鼻 ;OVA +RSV组 :OVA致敏 ,RSV滴鼻。第 1 6天 ,每组各 6只小鼠支气管肺泡灌洗作细胞计数及分类 ,酶链免疫吸附试验 (ELISA)测定白细胞介素 4(IL 4)、γ干扰素 (IFN γ)的含量 ;余 4只取肺组织用于病理分析和提取总RNA ,经逆转录 聚合酶链反应 (RT PCR)测IL 4、IL 5、IFN γ的mRNA表达量。结果　 (1 )支气管肺泡灌洗液 (BALF)中细胞总数 :单纯RSV组为 (1 4 5±5 4)× 1 0 6 /ml、OVA +RSV组为 (1 6 8± 4 9)× 1 0 6 /ml,与对照组 [(7 7± 2 4)× 1 0 6 /ml]比较差异有显著性 (P <0 0 5) ;淋巴细胞RSV组为 0 63± 0 0 5、OVA +RSV组为 0 77± 0 0 9,与OVA组 (0 36± 0 0 3)、对照组 (0 2 8± 0 0 5)比较差异有显著性 (P <0 0 5) ;嗜酸细胞 :OVA +RSV组 (0 0 690± 0 0 1 0 0 )与其它三组 (0 0 0 30± 0 0 0 1 0、0 0 0 90± 0 0 0 50、0 0 1 0 0± 0 0 0 4 0 )比较差异也有显著性 (P均 <0     

Differential interleukin-10 expression in interferon regulatory factor-1 deficient mice during Plasmodium berghei blood-stage infection

Mice deficient of functional interferon regulatory factor-1 (IRF-1-/-) by targeted gene disruption infected with a lethal murine malaria strain, Plasmodium berghei ANKA survived longer than its wild-type littermates despite the inability to induce appreciable amounts of interferon-gamma (IFN-gamma) and nitric oxide. In addition, infected IRF-1-/- mice displayed less organ injury with reduced necrosis and inflammation. Both wild-type and IRF-1-/- mice treated with exogenous interleukin-12 (IL-12) suffered extensive organ damage with corresponding up regulation of IFN-gamma, suggesting the pathogenic potential of IL-12 and IFN-gamma. IL-10 is a cytokine produced by CD4+ T lymphocytes belonging to the Th2 subset. Expression of IL-10 in the wild-type mice correlated with the severity of the infection, with higher mRNA expression towards the later stage of infection. In contrast to the wild-type mice, IL-10 levels in the IRF-1-/- mice were induced early in the infection and decreased gradually as the infection progressed. Both untreated and IL-12 treated wild-type mice appeared to follow a Th1-like immune response early in the infection and a Th2-like immune response later in the infection. However, the IRF-1-/- mice were able to launch an altered immune response with a Th2-like immune response early in the infection. These findings suggest that IL-10 expression in the IRF-1-/- mice during the early stage of P. berghei ANKA infection could play an important role in suppressing pathogenic effects of a cell mediated immune response and promoting protective immunity against the parasite.     

哮喘患者外周血单个核细胞中Thh／Th2类细胞因子的偏移状？…

目的 观察支气管哮喘患者外周血单个核细胞（ＰＢＭＣ）中Ｔ输助淋巴细胞两个功能性亚群（Ｔｈ１／Ｔｈ２）的功能状态及红霉素对其的影响。方法 ２３例哮喘患者及正常对照组１０名,采用逆转录聚合酶链反应（ＲＴ－ＰＣＲ）技术,以白细胞介素２（ＩＬ－２）和干扰素γ（ＩＮＦ－γ）代表Ｔｈ１类细胞因子,ＩＬ－４、６、１０代表Ｔｈ２类细胞因子,分别检测了两组ＰＢＭＣ加红霉素体外培养前、后上述各种因子ｍＲＮＡ的表达。结     

Role of Th1 and Th2 cytokines in regulating the liver injury induced by delayed-type hypersensitivity to picryl chloride

AIMS/BACKGROUND: We have previously reported that a new model of liver injury induced in mice by delayed-type hypersensitivity (DTH) to picryl chloride (PCl) mimicks the pathogenesis of human hepatitis. This liver injury is mediated by CD4+ T cells. The interaction between lymphocyte function associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) is an essential process for hepatocyte (HC) damage. The present study was undertaken to reveal the role of Th1 and Th2-like cytokines in regulating the liver injury. METHODS: The kinetics of cytokine production were examined by ELISA and RT-PCR after the elicitation of liver injury for both serum protein and liver mRNA expression, respectively. A co-culture assay between liver nonparenchymal cells (NPC) and HC was conducted to evaluate the cytokine regulation on the cell-cell interaction. Expression of LFA-1 on NPC and ICAM-1 on HC were examined by FACScan and ELISA, respectively. RESULTS: Serum IL-2 and IFN-gamma showed a peak production at 6 and 12 h, while IL-5 and IL-4 reached their maximum levels at 18 and 24 h after induction of liver injury, respectively. Liver mRNA expression of IFN-gamma and IL-4 had a similar time course to their corresponding products. Both recombinant murine IFN-gamma and IL-2 triggered the hepatotoxicity of NPC or spleen cells at 0 h. In this case, an increased expression of both LFA-1 on NPC and ICAM-1 on HC was also observed. In contrast, IL-4 and IL-5 completely abolished the hepatotoxicity of NPC at 12 h without influencing the adhesion molecules. CONCLUSION: Th1 and Th2 may be involved in regulating liver injury. Th1/Th2 balance may critically contribute to the production of the liver injury or recovery from it.     

ST2 gene induced by type 2 helper T cell (Th2) and proinflammatory cytokine stimuli may modulate lung injury and fibrosis

The authors have investigated gene expression of ST2 in the lung tissue of a bleomycin (BLM)-induced lung fibrosis model in vivo and in a human lung fibroblast cell line, WI38, and a human type II alveolar epithelial cell line, A549, reacting to proinflammatory and type 2 helper T cell (Th2)-type cytokine stimuli in vitro. The lung mRNA expression of interleukin (IL)-4, IL-5, IL-1beta, and tumor necrosis factor (TNF)-alpha increased significantly at day 7 after instillation of BLM, whereas interferon (IFN)-gamma mRNA expression did not increase. ST2 and transforming growth factor (TGF)-beta1 mRNA expression of the lung increased significantly between days 7 and 21, and increased to maximal levels at day 14 post-BLM challenge. ST2 mRNA expression statistically correlated with TGF-beta 1 mRNA expression. In addition, the combination of IL-1 beta, TNF-alpha, and IL-4 had an additive effect on ST2 mRNA expression from A549 cells and WI38 cells. These findings suggest that soluble ST2 gene may increase, possibly reflecting the development of the inflammatory process and the Th2-type immune response in the fibrotic lung tissue, and may modulate a process of pulmonary fibrosis.     

NO-aspirin protects from T cell-mediated liver injury by inhibiting caspase-dependent processing of Th1-like cytokines

BACKGROUND & AIMS: Concanavalin A (con A)-induced hepatitis is an immunomediated disease in which assembly of CD4(+) T cells and T helper (Th)1-like cytokines causes Fas-mediated liver cell death. Nitric oxide (NO) modulates Th1 response in vitro. NCX-4016 is an NO-aspirin derivative that spares the gastrointestinal tract and shares molecular targets with NO. The aim of this study was to investigate whether this NO-aspirin modulates Th1-like response induced by con A. METHODS: BALB/c mice were injected with 0.3 mg con A per mouse alone or in combination with NO-aspirin (18-100 mg/kg) or aspirin (10-55 mg/kg). RESULTS: NO-aspirin, but not aspirin, caused a dose-dependent protection against liver damage induced by con A. At a dose of 100 mg/kg, NO-aspirin caused a 40%-80% reduction of interleukin (IL)-1beta, IL-12, IL-18, interferon (IFN)-gamma, and tumor necrosis factor alpha production without affecting cytokine messenger RNA expression. NO-aspirin prevented Fas, Fas ligand, and IL-2 receptor up-regulation on spleen lymphocytes and Fas ligand on hepatocytes and caused the S-nitrosylation/inhibition of IL-1beta-converting enzyme-like cysteine proteases (caspases) involved in the processing and maturation of IL-1beta and IL-18. IL-18 immunoneutralization prevented IFN-gamma release and protected from liver injury induced by con A. In contrast to a selective caspase 1 inhibitor, zVAD.FMK, a pancaspase inhibitor, prevented IFN-gamma release and protected the liver from injury. CONCLUSIONS: Th1-like response induced by con A is mediated by IL-18 and requires activation of multiple caspases. NCX-4016 causes the S-nitrosylation/inhibition of caspases involved in cytokine production. Inhibition of Th1-like response is a new anti-inflammatory mechanism of action of NO-aspirin.     

Preventive effect of hochu-ekki-to, a Japanese herbal medicine, on bleomycin-induced lung injury in mice

OBJECTIVE: Pulmonary fibrosis is thought to be closely associated with the T-helper type-2 (Th2) immune response. Recent studies have shown that hochu-ekki-to (TJ-41), a Japanese herbal medicine, may correct the Th1/Th2 imbalance skewed to Th2. The present study was designed to investigate the preventive effect of TJ-41 on the development of bleomycin (BLM)-induced lung injury in mice. METHODS: Female C57BL/6 mice were divided into a group given ordinary feed and another group given the same feed plus TJ-41 mixed in at a dose of 1 g/kg/day. Both groups were maintained on this diet for 8 weeks before and 5 weeks after administration of 2 mg/kg BLM intratracheally. RESULTS: Mortality after BLM-induced lung injury was significantly lower in the TJ-41-treated mice. The hydroxyproline content and fluid content in the lung on day 35 was significantly lower in the TJ-41-treated mice. Histologically, TJ-41 reduced the number of infiltrating cells, thus ameliorating the destruction of the lung architecture, and attenuated the lung fibrosis score. Furthermore, TJ-41 inhibited the expression of the interleukin-5/interferon-gamma mRNA ratio in the lung on day 7. CONCLUSIONS: Treatment with TJ-41 partially prevented experimental lung fibrosis through the correction of the Th1/Th2 imbalance skewed to Th2.     

母牛分支杆菌菌苗对结核病小鼠Th1/Th2 细胞动力学及诱导型一氧化氮合酶 表达影响的研究

目的　从分子病理学角度探讨母牛分支杆菌菌苗 (以下简称母牛菌苗 )的免疫调节机制。方法　将BALB/C小鼠随机分为 3组 :单纯攻毒组 (A)、母牛菌苗免疫攻毒组 (B)和正常对照组(N)。经尾静脉注射H37RV 建立结核病小鼠模型 ,母牛菌苗由腹腔注射。肉眼观察肺脏病变指数并采用免疫组化染色和常规HE染色 ,探讨IFN γ、IL 4、iNOS表达与肺脏组织损伤的类型和程度的关系。结果　结核病小鼠病变弥漫 ,伴有灶性干酪坏死 ,免疫组织化学染色结果显示在炎性渗出及肉芽肿内IFN γ阳性细胞随时间推移逐渐增多 ,至第 6周达高峰 (0 0 5 8± 0 0 10 ) ,与正常对照组比较有非常显著性差异 (0 0 0 5± 0 0 2 0 ,P <0 0 1)。此后为Tho平衡期 ,在肺损伤组织中IFN γ和IL 4阳性细胞基本相当。iNOS表达在急性期增多慢性期减少。母牛菌苗免疫攻毒组小鼠肺组织病变 ,以增殖结节、淋巴样结节为主 ,未见坏死病变 ,免疫反应表现为 :感染全过程中以Th1应答为主 ,即IFN γ阳性细胞逐渐增多 ,第 8周达高峰 (0 0 5 8± 0 0 10 ) ,IL 4阳性细胞一直维持在低水平 ,未出现Tho平衡期。iNOS表达一直维持在高水平。结论　母牛菌苗调节结核病小鼠免疫的可能机制为 :启动Th1应答 ,抑制Th2应答 ,激活iNOS活性 ,增强机体保护性免疫。     

红霉素对肺纤维化大鼠核因子κB活性及细胞因子mRNA表达 …

目的 探讨红霉素治疗肺纤维化的机制和疗效。方法 实验用Ｗｉｓｔａｒ大鼠８１只,分成三组;正常一附属博莱霉素模型组和红霉素治疗组。每组２７只。气管内注入单剂量博莱霉素制备大鼠肺纤维化模型,于博莱霉素气管内注入后每日给予口红霉素治疗,各组动物分别于气管内用药后第４,７和２８天处死动物。用凝胶电泳迁移实验测定肺泡巨噬细胞的核因子（ＮＦ）－κＢ活性;     

Polyinosinic-polycytidylic acid attenuates hepatic fibrosis in C57BL/6 mice with Schistosoma japonicum infection

The development of hepatic fibrosis is the principal cause of morbidity and mortality in human beings infected with schistosoma. In this study, we investigated the effect of polyinosinic-polycytidylic acid (poly I:C) on Schistosoma japonicum (S. japonicum) egg-induced liver fibrosis. S. japonicum cercariae infected mice were injected with poly I:C at the onset of egg granuloma formation (early phase poly I:C treatment) or after the formation of liver fibrosis (late phase poly I:C treatment). Our results showed that both early and late phase poly I:C treatment significantly reduced collagen deposition and hepatic stellate cell activation in the liver. Poly I:C is one of the most effective adjuvants for Th1 type responses, and its protective effect on liver fibrosis was accompanied by increased IFN-α, IFN-β, IFN-γ, IL-12, TNF-α, and IL-10 mRNA expression, and decreased IL-4 and IL-5 mRNA expression. Moreover, poly I:C injection also enhanced the mRNA expression of natural killer group 2 member D (NKG2D) and tumor necrosis factor related apoptosis-inducing ligand (TRAIL). Therefore, it is indicated that poly I:C can significantly attenuate S. japonicum egg-induced hepatic fibrosis, which may be partly dependent on the increased Th1 response and decreased Th2 response.