生长激素诱导心肌细胞外信号调节酶激活及其上游调控

目的和方法：用生长激素（ＧＨ）刺激培养的新生大鼠心肌细胞,用含ＭＢＰ凝胶分离法测定细胞外信号调节酶（ＥＲＫｓ）活性,用Ｗｈａｔｍａｎ Ｐａｐｅｒ Ｆｉｌｔｅｒ法测定Ｒａｆ－１活性,观察ＧＨ是否激活心肌细胞Ｒａｆ－１－ＥＲＫ级联反应。观察负显突变Ｒａｓ质粒（Ｄ．Ｎ．Ｒａｓ）与ＨＡ－ＥＲＫ２质粒复合转染或有关抑制剂对ＧＨ诱导ＥＲＫ激活的影响。结果：ＧＨ以时间和浓度依赖性方式激活心肌细胞ＥＲＫ１和ＥＲＫ     

人外周血树突状细胞在LAK抗HPBALL细胞中作用的研究

为探讨树突状细胞（ＤＣ）在ＬＡＫ抗ＨＰＢＡＬＬ细胞中的作用，采用多因素、多水平的杀伤试验，同时以光镜、电镜观察ＤＣ、ＬＡＫ、ＨＰＢＡＬＬ相互作用的形态特征及ＤＮＡ断端标记法检测瘤细胞是否凋亡。结果表明：（１）ＤＣ无直接杀伤ＨＰＢＡＬＬ作用。（２）５×１０５～１×１０７／ＬＤＣ有增强不同Ｅ／ＴＬＡＫ杀伤活性的趋势，而１×１０７～５×１０７／ＬＤＣ对ＬＡＫ活性有抑制趋势。（３）ＤＣ、ＬＡＫ杀伤ＨＰＢＡＬＬ的最佳组合条件为：ＤＣ培养４ｄ、浓度５×１０６／Ｌ，ＬＡＫＥ／Ｔ＝１０／１，ｒＩＬ－２＝０。（４）光镜、电镜下均可见ＤＣ的突起与ＬＡＫ、ＨＰＢＡＬＬ细胞紧密接触形成细胞簇。（５）ＤＮＡ断端标记法显示瘤细胞呈末端脱氧核糖核酸转移酶阳性反应。结论：ＤＣ对ＬＡＫ杀伤ＨＰＢＡＬＬ活性具有双向调节作用     

IL-6对大鼠急性髓系白血病R2细胞的增殖抑制及分化诱导作用

重组人白细胞介素６（ｒｈＩＬ－６）可抑制大鼠急性髓系白血病（ＡＭＬ）Ｒ２细胞的体外生长（ＩＣ５０１００ｎｇ／Ｌ），并在１０ｎｇ／Ｌ～１μｇ／Ｌ的剂量范围内诱导Ｒ２细胞向终末方向分化。诱导后的Ｒ２细胞具有单核巨噬细胞的形态特征；且非特异性酯酶（ＮＳＥ）及酸性醋酸酯酶（ＡＮＡＥ）的活性增强，而过氧化物酶（ＰＯＸ）的活性却一直很低。经典型的ＤＮＡ梯状条带及凋亡小体证实，≥１μｇ／ＬｒｈＩＬ－６亦可诱导Ｒ２细胞凋亡。我们认为，Ｒ２细胞是研究ＩＬ－６信号转导通路及ＡＭＬ细胞分化机制的一个很好模型。     

PHA－LAK与常规LAK细胞生物学特性的比较

本文对来自正常人Ｏ型外周血单个核细胞（ＰＢＭＣ）,经ＰＨＡ预刺激４８小时,然后用ｒＩＬ－２诱导的ＬＡＫ细胞（ＰＨＡ－ＬＡＫ）和直接用ｒＩＬ－２诱导的常规制备的ＬＡＫ细胞的生物学特性进行了比较。结果表明ＰＨＡ－ＬＡＫ和常规ＬＡＫ在细胞形态、核型和细胞化学等方面均相似;而在增殖能力、体外存活时间、细胞毒活性方面ＰＨＡ－ＬＡＫ明显优于常规ＬＡＫ。ＦＡＣＳ表型分析表明：ＰＨＡ－ＬＡＫ的表型以ＣＤ３＋ＣＤ８＋为主,而常规ＬＡＫ则以ＣＤ３＋ＮＫＨ￣＋＿１为主,且ＰＨＡ－ＬＡＫＩＬ－２Ｒ的表达水平高于常规ＬＡＫ。采用ＰＨＡ－ＬＡＫ可较好地解决ＬＡＫ细胞的数量和活性问题,这在ＩＬ－２／ＬＡＫ疗法中有重要的实用价值。     

PHA－LAK与常规LAK细胞生物学特性的比较

本文对来自正常人Ｏ型外周血单个核细胞（ＰＢＭＣ）,经ＰＨＡ预刺激４８小时,然后用ｒＩＬ－２诱导的ＬＡＫ细胞（ＰＨＡ－ＬＡＫ）和直接用ｒＩＬ－２诱导的常规制备的ＬＡＫ细胞的生物学特性进行了比较。结果表明ＰＨＡ－ＬＡＫ和常规ＬＡＫ在细胞形态、核型和细胞化学等方面均相似;而在增殖能力、体外存活时间、细胞毒活性方面ＰＨＡ－ＬＡＫ明显优于常规ＬＡＫ。ＦＡＣＳ表型分析表明：ＰＨＡ－ＬＡＫ的表型以ＣＤ３＋ＣＤ８＋为主,而常规ＬＡＫ则以ＣＤ３＋ＮＫＨ￣＋＿１为主,且ＰＨＡ－ＬＡＫＩＬ－２Ｒ的表达水平高于常规ＬＡＫ。采用ＰＨＡ－ＬＡＫ可较好地解决ＬＡＫ细胞的数量和活性问题,这在ＩＬ－２／ＬＡＫ疗法中有重要的实用价值。     

IL—2—绿脓杆菌外毒素融合蛋白增强杀伤细胞活性

实验证实了白细胞介素２－绿脓杆菌外毒素融合蛋白ＩＬ２－ＰＥ４０ＲＥＤＬＫ、ＩＬ２－ＰＥ４０ＫＤＥＬ、ＩＬ２－ＰＥ６６4GluＲＥＤＬＫ、ＩＬ２－ＰＥ６６4GluＫＤＥＬ对含高亲和力ＩＬ－２受体靶细胞的杀伤效应是借助于ＩＬ－２与其受体的特异性结合和ＰＥ的杀伤活性介导的，而且同一靶细胞对这些融合蛋白的敏感性有较大的差异，对人外周血ＰＨＡ体外活化的淋巴母细胞的杀伤活性，ＩＬ２－ｐＥ６６4GluＫＤＥＬ要比ＩＬ２－ＰＥ４０ＲＥＤＬＫ强约４０倍，还发现若将ＩＬ２－ＰＥ融合蛋白羧基末端的ＲＥＤＬＫ氨基酸突变为ＫＤＥＬ可增强其杀伤细胞的活性，对ＣｏｎＡ活化的小鼠脾母细胞的杀伤活性，ＩＬ２－ＰＥ４０ＫＤＥＬ要比ＩＬ２－ｐＥ４０ＲＥＤＬＫ强８倍。     

HCMV感染对单核细胞HLA－DR表达的影响

本文采用细胞ＥＬＩＳＡ法，研究发现人巨细胞病毒（ＨＣＭＶ）感染对单核细胞ＨＬＡ－ＤＲ的影响。结果表明ＨＣＭＶ感染后１ｄ，单核细胞ＨＬＡ－ＤＲ表达显著增高（Ｐ＜０．０１），以后逐渐降低，ｄ５降至对照水平；ＩＦＮγ（５００Ｕ／ｍｌ）．ＴＮＦ（２５０Ｕ／ｍｌ）、ＩＬ－６（５００／ｍｌ）、ＩＬ－１（５００／ｍｌ）均能不同程度地刺激单核细胞ＨＬＡ－ＤＲ表达；ＨＣＭＶ感染后，细胞因子刺激ＨＬＡ－ＤＲ表达的水平在感染后ｄ５，较对照组均显著降低（Ｐ＜０．０１）；ＩＬ－１＋ＩＦＮ－γ及ＴＮＦ＋ＩＦＮ－γ在刺激单核细胞ＨＬＡ－ＤＲ表达时有协同作用；ＨＣＭＶ感染后，ＩＦＮ－γ＋ＩＬ－１及ＴＮＦ＋ＩＦＮ协同刺激单核细胞ＨＬＡ－ＤＲ表达水平较对照组显著降低（Ｐ＜０．０１）。结果提示：在ＨＣＭＶ感染引起免疫抑制过程中，其引起单核细胞ＨＬＡ－ＤＲ表达降低是一重要机制。     

慢性乙型肝炎,肝硬化患者外周血LAK细胞活性和sIL—2R测定的意义

采用＾３Ｈ－ＴｄＲ释放法测定５１例慢性肝病患者（ＣＰＨ１０例、ＣＡＨ２３例、ＬＣ１８例）外周血ＬＡＫ细胞活性，并用酶联法测定患者血清中ｓＩＬ－２Ｒ含量；与２９例正常对照组比较，发现肝病患者ＬＡＫ活性降低，ＨＢＶＤＮＡ阳性组ＬＡＫ活性较阴性组低（Ｐ〈０．０５），ｓＩＬ－２Ｒ增高，且慢性肝病组ＬＡＫ活性与ｓＩＬ－２Ｒ水平呈负相关，说明ＬＡＫ活性与机体免疫功能状态有关，ＨＢＶ的复制和高浓度的ｓＩＬ－２Ｒ     

HCMV感染对单核细胞HLA－DR表达的影响

本文采用细胞ＥＬＩＳＡ法，研究发现人巨细胞病毒（ＨＣＭＶ）感染对单核细胞ＨＬＡ－ＤＲ的影响。结果表明ＨＣＭＶ感染后１ｄ，单核细胞ＨＬＡ－ＤＲ表达显著增高（Ｐ＜０．０１），以后逐渐降低，ｄ５降至对照水平；ＩＦＮγ（５００Ｕ／ｍｌ）．ＴＮＦ（２５０Ｕ／ｍｌ）、ＩＬ－６（５００／ｍｌ）、ＩＬ－１（５００／ｍｌ）均能不同程度地刺激单核细胞ＨＬＡ－ＤＲ表达；ＨＣＭＶ感染后，细胞因子刺激ＨＬＡ－ＤＲ表达的水平在感染后ｄ５，较对照组均显著降低（Ｐ＜０．０１）；ＩＬ－１＋ＩＦＮ－γ及ＴＮＦ＋ＩＦＮ－γ在刺激单核细胞ＨＬＡ－ＤＲ表达时有协同作用；ＨＣＭＶ感染后，ＩＦＮ－γ＋ＩＬ－１及ＴＮＦ＋ＩＦＮ协同刺激单核细胞ＨＬＡ－ＤＲ表达水平较对照组显著降低（Ｐ＜０．０１）。结果提示：在ＨＣＭＶ感染引起免疫抑制过程中，其引起单核细胞ＨＬＡ－ＤＲ表达降低是一重要机制。     

IL—6对大鼠急性髓系白血病R2细胞的增殖抑制及分化诱 …

重组人白细胞介素６（ｒｈＩＬ－６）可抑制大鼠急性髓系白血病（ＡＭＬ）Ｒ２细胞的体外生长（ＩＣ５０ １００ｎｇ／Ｌ），并在１０ｎｇ／Ｌ￣１μｎ／Ｌ的剂量范围内诱导Ｒ２细胞向终末方向分化。诱导后的Ｒ２细胞具有单核巨噬细胞的形态特征；且非特异性酯酶（ＮＳＥ）及酸性醋酸酯酶（ＡＮＡＥ）的活性增强，而过氧化物酶（ＰＯＸ）的活性却一直很低。经典型的ＤＮＡ梯状条带及凋亡小体证实，≥１μｇ／Ｌ ｒｈＩＬ－６亦可诱     

ERK1/2信号通路参与瘦素促人γδT细胞增殖调控

为探讨ERK1/2信号通路在瘦素促进人γδT细胞增殖中的作用机制。我们用MTT法观察不同浓度瘦素促γδT细胞的增殖效应,以及用ERK1/2特异性抑制剂PD98059阻断ERK1/2信号通路对瘦素促细胞增殖效应的影响,Western blot法检测瘦素干预对ERK1/2、P-ERK1/2蛋白表达水平的影响。结果显示,瘦素在一定浓度范围内促进人γδT细胞增殖。瘦素可使ERK1/2信号通路中的靶蛋白发生磷酸化激活,用PD98059阻断ERK1/2信号通路可显著抑制瘦素促细胞的增殖效应,亦可抑制瘦素对γδT细胞ERK1/2蛋白磷酸化。因此,我们认为瘦素促人γδT细胞增殖效应可能与激活ERK1/2信号通路有关。     

叶酸通过下调ERK1/2信号通路抑制血管平滑肌细胞增殖和迁移

目的:探讨叶酸(folic acid,FA)对血管平滑肌细胞(VSMCs)增殖和迁移的影响及其机制。方法:取SD大鼠的主动脉,采用组织贴块法培养VSMCs,随机分组进行实验。采用CCK-8和Ed U法检测叶酸对VSMCs活力和增殖能力的影响。采用划痕实验和Transwell法检测叶酸对VSMCs迁移和侵袭的影响。采用Western blot法检测细胞增殖核抗原(PCNA)蛋白表达以及血小板源性生长因子受体(PDGFR)和细胞外信号调节激酶1/2(ERK1/2)蛋白的磷酸化水平。结果:叶酸抑制血小板源性生长因子(PDGF)诱导的VSMCs的活力,并呈浓度依赖性(P0.05)。叶酸抑制PDGF诱导的VSMCs的迁移,并呈浓度依赖性(P0.05)。叶酸降低PCNA表达和PDGFR磷酸化水平,并抑制PDGF激活的ERK1/2信号通路。结论:叶酸降低PDGF诱导的VSMCs PCNA和p-PDGFR蛋白水平,下调ERK1/2信号通路,从而抑制VSMCs的增殖和迁移。     

Trypanosoma cruzi infection activates extracellular signal-regulated kinase in cultured endothelial and smooth muscle cells

Trypanosoma cruzi infection causes cardiomyopathy and vasculopathy. We examined the consequence of this infection for the mitogen-activated protein kinase (MAPK) pathways, which regulate cell proliferation in cultured human umbilical vein endothelial and vascular smooth muscle cells. Infection of these cells resulted in activation of extracellular signal-regulated kinases 1and 2 (ERK1/2) but not c-Jun N-terminal kinase or p38 MAPK. Treatment of these cells with the MAPK kinase inhibitor PD98059 prior to infection blocked the increase in phosphorylated ERK1/2 seen with infection. Heat-killed parasites did not activate ERK1/2, indicating that activation of ERK1/2 was dependent on infection of these cells by live parasites. Furthermore, transfection with dominant-negative Raf(301) or Ras(N17) constructs reduced the infection-associated levels of phospho-ERK1/2, indicating that the activation of ERK1/2 involved the Ras-Raf-ERK pathway. Infection also resulted in an increase in activator protein 1 (AP-1) activity, which was inhibited by transfection with a dominant-negative Raf(301) construct. T. cruzi-infected endothelial cells secreted endothelin-1 and interleukin-1beta, which activated ERK1/2 and induced cyclin D1 expression in uninfected smooth muscle cells. These data suggest a possible molecular paradigm for the pathogenesis of the vasculopathy and the cardiovascular remodeling associated with T. cruzi infection.     

Fluid shear stress promotes osteoblast proliferation via the Gαq–ERK5 signaling pathway

Fluid shear stress (FSS) is a ubiquitous mechanical stimulus that potently promotes osteoblast proliferation. Previously, we reported that extracellular signal–regulated kinase 5 (ERK5) is essential for FSS-induced osteoblast proliferation. However, the precise mechanism by which FSS promotes osteoblast proliferation via ERK5 activation is poorly understood. The aim of this study was to determine the critical role of Gαq in FSS-induced ERK5 phosphorylation and osteoblast proliferation, as well as the downstream targets of the Gαq–ERK5 pathway. MC3T3-E1 cells were transfected with 50 nM Gαq siRNA, treated with 5 mM XMD8-92 (a highly selective inhibitor of ERK5 activity), and/or exposed to FSS (12 dyn/cm²). Cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The protein expression levels of Gαq, P-ERK5, ERK5, Cyclin B1, and CDK1 were analyzed by Western blot. Physiological FSS exposure for 60 min remarkably promoted MC3T3-E1 cell proliferation, however, this effect was suppressed by siRNA-mediated Gαq knockdown or inhibition of ERK5 activity by XMD8-92 treatment, suggesting that Gαq and ERK5 might modulate FSS-increased osteoblast proliferation. Furthermore, ERK5 phosphorylation was dramatically inhibited by Gαq siRNA. In addition, our study further revealed that FSS treatment of MC3T3-E1 cells for 60 min markedly upregulated the protein expression levels of Cyclin B1 and CDK1, and this increased expression was predominantly blocked by Gαq siRNA or XMD8-92 treatment. We propose that FSS acts on the Gαq–ERK5 signaling pathway to upregulate Cyclin B1 and CDK1 expression, thereby resulting in MC3T3-E1 cell proliferation. Thus, the Gαq–ERK5 signaling pathway may provide useful information regarding the treatment of bone metabolic disease.     

单核细胞趋化蛋白-1经细胞外信号调节激酶通路对肺癌A549细胞 增殖、侵袭转移的影响及机制*

目的：研究单核细胞趋化蛋白-1（ MCP-1）对非小细胞肺癌增殖、侵袭转移能力的影响及可能的作用 机制。方法：体外培养肺癌细胞株A549。细胞分为对照组,MCP-1 组（25、50、75、100 ng/mL）,MCP-1 （75 ng/mL）+PD98059 组（100 μmol/mL）,抑制剂PD98059 组（100 μmol/L）。MTT 法检测细胞增殖活力,细胞划痕、 Transwell 侵袭实验分析细胞迁移侵袭能力。免疫印迹检测细胞外信号调节激酶（ t-ERK）、磷酸化细胞外信号调 节激酶（ p-ERK）、基质金属蛋白酶-14（ MMP-14）、基质金属蛋白酶-2（ MMP-2）及N- 钙黏蛋白（ N-cadherin） 的表达。结果：与对照组相比,MCP-1 明显促进A549 细胞的增殖、侵袭与转移;免疫印迹结果显示,MCP-1 可 上调p-ERK、MMP-14、MMP-2 及N-cadherin 蛋白的表达;应用ERK抑制剂PD98059 可阻断上述作用。ERK总 蛋白表达量差异无统计学意义。结论：MCP-1 经ERK通路上调MMP-14、MMP-2 及N-cadherin 蛋白表达,促进 肺癌A549 细胞增殖、侵袭与转移。     

Stimulation of extracellular signal-regulated kinases and proliferation in the human gastric cancer cells KATO-III by obestatin

Obestatin, the ghrelin-associated peptide, activates cell proliferation in the gastric cancer cell line KATO-III. The results showed that this peptide induced cell proliferation by mitogen-activated kinase kinase/extracellular signal-regulated kinases1/2 (ERK1/2) phosphorylation. A sequential analysis of the obestatin transmembrane signalling pathway indicated that the ERK1/2 activity is partially blocked after preincubation of the cells with pertussis toxin, as well as by wortmannin (an inhibitor of phosphoinositide 3-kinase (PI3K)), staurosporine (an inhibitor of protein kinase C (PKC)) and 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2, which inhibits the non receptor tyrosine kinase Src). Upon administration of obestatin, the intracellular levels of phospho-PKCepsilon- and theta-isoenzymes rise with similar time-courses, from which PKCepsilon appears to be the responsible for ERK1/2 response. Based on the experimental data, a signalling pathway involving the consecutive activation of G(i), PI3K, novel PKCepsilon and Src for ERK1/2 activation is proposed. These results point to a functionally active peptide that regulates proliferation of the gastric cancer cells KATO-III.     

Interleukin 10 Induced C-FOS Expression in Human B Cells by Activation of Divergent Protein Kinases

IL-10 is a potent mediator of human B cell growth and plasma cell formation However, signal transduction of IL-10 in B cells is poorly understood. In this study the effect of IL-10 on the expression of the protooncogene c-fos was investigated, because Fos plays a potential role in the regulation of B cell proliferation and differentiation. B cells were purified from buffy coat preparations of healthy blood donors by positive selection using an anti CD20 monoclonal antibody and a MiniMACS separation unit. B cells were prestimulated with SAC for 48 hrs Then, cells were incubated with medium or IL-10 (100 ng/ml) for 10 to 120 min. RNA was extracted by phenol/chloroform and c-fos expression was analyzed by PCR assisted mRNA assay. A significant 2–4 fold increase of c-fos expression was observed within 30 min of stimulation with IL-10 (p < 0,01). After 2 hrs c-fos expression declined to basal levels The effect of IL-10 was dose-dependent with a maximum stimulation using 100 ng/ml of IL-10. The IL-10 effect on c-fos expression was not blocked by polymyxin B. Using the tyrosine kinase inhibitor genistein (10μM) a complete inhibition of IL-10 induced c-fos expression was observed In addition, H-7 (10μM), a specific inhibitor of serine/threonin kinases, significantly blocked IL-10 mediated c-fos expression (p < 0,05). In conclusion, these data show that IL-10 induces c-fos expression in human B-cells by activation of tyrosine and serine/threonin kinases. Since this is the first report on IL-10 induced signal transduction, these data may help to identify the intracellular mechanisms by which IL-10 stimulates human B-cells.     

胰岛素样生长因子1对早孕滋养细胞增殖的作用及机制研究

目的探讨胰岛素样生长因子1(IGF-1)对体外培养的早孕滋养细胞增殖的影响,以及滋养细胞增殖的细胞内信号转导机制。方法取原代培养传代后生长良好的滋养层细胞,加入不同浓度的IGF-1继续培养,用四唑盐(MTT)比色法测定细胞的增殖活性,并且以ERK(细胞外信号调节蛋白激酶)通路的特异性抑制剂U0126处理细胞,间接反映ERK通路的作用。结果①与对照组相比,IGF-1浓度≥1nM时,其促进滋养细胞增殖效果有显著性意义(P<0.05),且在0.1-100nM范围内,此种作用与浓度呈正相关。②ERK通路阻滞剂U0126可抑制滋养细胞的增殖(P<0.05),并且可显著抑制IGF-1对滋养细胞的促增殖作用(P<0.05)。结论①IGF-1对滋养层细胞的增殖活性具有促进作用。②ERK通路可能是滋养细胞增殖过程中的主要信号转导通路之一。     

青蒿琥酯通过抑制ERK1/2蛋白活化负性调控HSC-T6细胞cyclin D1的表达和AP-1活性

目的: 通过观察青蒿琥酯(artesunate,Art)对肝星状细胞(hepatic stellate cells,HSCs)细胞外信号调节蛋白激酶1/2(extracellular signal-regulated kinase 1/2,ERK1/2)、激活蛋白1(activator protein 1,AP-1)和细胞周期蛋白D1(cyclin D1)的影响,探讨Art抗肝纤维化的分子机制。方法: 用血小板源性生长因子BB(platelet-derived growth factor BB, PDGF-BB)诱导HSC-T6细胞的增殖。实验分为对照组、PDGF-BB组、PDGF-BB+Art组(Art终浓度6.25 mg/L、25 mg/L、50 mg/L)和PDGF-BB+ERK抑制剂PD98059组。ELISA法测定细胞上清液中Ⅰ型胶原的含量,RT-PCR检测各组ERK1/2和cyclin D1 mRNA水平变化,Western blotting法检测各组p-ERK1/2和cyclin D1蛋白表达水平,凝胶电泳迁移率实验(EMSA)检测AP-1的活性。结果: (1)PDGF-BB 可明显促进HSC-T6细胞的增殖,PDGF-BB+Art各剂量组和PDGF-BB+PD98059均可抑制HSC-T6细胞上清液中Ⅰ型胶原的含量(P<0.05,P<0.01)。(2)PDGF-BB+Art组(50 mg/L)ERK1/2 mRNA的表达低于PDGF-BB组(P<0.05),其中PDGF-BB+PD98059组ERK1/2 mRNA的表达最低(P<0.01);PDGF-BB+Art组(25 mg/L、50 mg/L)和PDGF-BB+PD98059组cyclin D1 mRNA的表达明显低于PDGF-BB组(P<0.05,P<0.01)。(3)p-ERK1/2、cyclin D1蛋白表达水平在PDGF-BB组最高,而PDGF-BB+Art各剂量组和PDGF-BB+PD98059组降低(P<0.05,P<0.01)。(4)Art可使AP-1与DNA结合活性下降。结论: Art可抑制HSC-T6细胞增殖,其机制可能与其抑制ERK1/2蛋白活化从而降低AP-1的活性和下调cyclin D1的表达有关。