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1.
目的探讨阿托伐他汀对内皮细胞微粒(EMPs)诱导人脐静脉内皮细胞(HUVECs)细胞间黏附分子-1(ICAM-1)表达的影响及其与ERKl/2信号通路的关系。方法将HUVECs分为不同浓度EMPs作用组与阿托伐他汀干预组。应用Western印迹检测磷酸化ERK1/2和ICAM-1蛋白的表达,实时荧光定量PCR(qRT-PCR)检测ICAM-1 mRNA的表达。结果 EMPs可诱导HUVECs ICAM-1 mRNA和蛋白及磷酸化ERK1/2蛋白表达增加,且具有浓度和时间依赖关系(均P<0.01);阿托伐他汀及ERK1/2特异性抑制剂PD98059显著抑制EMPs诱导的HUVECs ICAM-1 mRNA和蛋白及磷酸化ERK1/2蛋白的表达(均P<0.01)。结论阿托伐他汀通过ERK1/2信号通路抑制EMPs诱导HUVECs ICAM-1表达。 相似文献
2.
通心络超微粉对高脂饮食兔胸主动脉NF-κB、胞间黏附分子1及血管细胞黏附分子1表达的影响 总被引:4,自引:0,他引:4
目的探讨通心络超微粉对高脂饮食兔胸主动脉NF-κB、胞间黏附分子1(ICAM-1)及血管细胞黏附分子1(VCAM-1)表达的影响。方法健康雄性新西兰白兔32只,随机分为空白对照组、模型组、阿托伐他汀组、通心络组四组。空白对照组,饲以普通饲料;模型组,饲以高脂饲料;阿托伐他汀组,饲以高脂饲料同时阿托伐他汀(3mg·kg^-1·d^-1)灌胃;通心络组,饲以高脂饲料同时通心络超微粉(0.31g·kg^-1·d^-1)灌胃,连续给药,于6周末免疫组织化学染色法检测主动脉壁中NF-κB核转位情况、ICAM-1及VCAM-1蛋白表达情况,RT—PCR法检测ICAM-1 mRNA及VCAM-1 mRNA表达。结果与空白对照组相比,模型组家兔主动脉壁中NF—KB核转位明显增加。ICAM-1、VCAM-1基因及蛋白表达明显增多(P〈O.01)。与模型组相比,通心络组与阿托伐他汀组家兔主动脉壁中NF-κB核转位明显减少、ICAM-1、VCAM-1基因及蛋白表达明显减少(P〈0.01或P〈0.05),通心络组显著少于阿托伐他汀组(P〈0.01)。结论通心络超微粉通过抑制NF-κB核转位进而降低ICAM-1、VCAM-1基因及蛋白表达,减轻动脉粥样硬化病理改变。 相似文献
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目的通过研究氧化应激和炎症反应探讨阿托伐他汀治疗动脉粥样硬化的非调脂作用机制。方法以高脂饲料和免疫刺激方法制备动脉粥样硬化家兔模型,给予0.435 mg/(kg.d)阿托伐他汀混悬液治疗1个月,观察家兔血清超氧化物歧化酶活性、丙二醛和氧化型低密度脂蛋白含量以及血凝素样氧化型低密度脂蛋白受体1、主动脉血管细胞黏附分子1、细胞间黏附分子1、单核细胞趋化蛋白1基因和蛋白表达的变化。结果与正常对照组比较,动脉粥样硬化模型组家兔血清超氧化物歧化酶活性显著下降(P<0.01),血清丙二醛、氧化型低密度脂蛋白含量明显升高(P<0.01);主动脉血凝素样氧化型低密度脂蛋白受体1、血管细胞黏附分子1、细胞间黏附分子1、单核细胞趋化蛋白1的mRNA和蛋白表达明显升高(P<0.05或P<0.01)。与模型组比较,阿托伐他汀组家兔血清超氧化物歧化酶活性显著升高(P<0.01),血清丙二醛、氧化型低密度脂蛋白含量均显著下降(P<0.01),主动脉血凝素样氧化型低密度脂蛋白受体1、血管细胞黏附分子1、细胞间黏附分子1、单核细胞趋化蛋白1的mRNA和蛋白表达明显下调(P<0.05或P<0.01)。结论阿托伐他汀具有抗氧化应激和炎症反应的作... 相似文献
4.
目的观察黄芩茎叶总黄酮(SSTF)对高脂血症兔主动脉血管细胞黏附分子(VCAM)-1、细胞间黏附分子(ICAM)-1表达的影响,探讨SSTF抗动脉粥样硬化(AS)的可能机制。方法 24只健康雄性家兔随机分为正常对照组(6只),喂养普通饲料,动脉粥样硬化模型组(18只),喂养高脂饲料。8w后,将AS模型组再随机分为模型组,继续喂养高脂饲料,SSTF治疗组,喂养高脂饲料并灌胃给予SSTF(100、200mg·kg-1.d-1),治疗4w后,处死家兔,测定各组家兔TC、TG、LDL-C,取主动脉做病理切片,免疫组化检测主动脉VCAM-1、ICAM-1的表达。结果 SSTF可以降低高脂饮食兔血清TC、TG、LDL-C水平,作用效果呈剂量依赖性。SSTF能够逆转动脉粥样程度、抑制VCAM-1、ICAM-1的表达。结论 SSTF具有抗AS作用,可能与通过下调VCAM-1、ICAM-1表达,从而抑制血管壁炎症反应有关。 相似文献
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目的:观察阿托伐他汀对氧化型低密度脂蛋白(ox-LDL)诱导的人脐静脉内皮细胞(HUVEC)增殖及白细胞介素-18(IL-18)分泌的影响.方法:体外培养的HUVEC株,第3~9代用于实验.实验分3组:①空白对照组;②ox-LDL组(100 mg/L);③阿托伐他汀组:先将阿托伐他汀0.01、0.05、0.1、0.5、1.0μmol/L分别,作用于内皮细胞4 h,然后加ox-LDL(100 mg/L)作用细胞24 h.采用细胞酶联免疫吸附分析检测细胞培养上清液IL-18含量;采用四唑盐比色法检测各孔的吸收度(OD),以评价增殖效果.结果:与空白对照组比较,100 mg/L ox-LDL抑制内皮细胞增殖(P<0.01),阿托伐他汀呈剂量依赖性地促进ox-LDL诱导的内皮细胞增殖(P<0.05,P<0.01).正常内皮细胞不分泌IL-18,而100 mg/L ox-LDL促进IL-18分泌.0.01/μmol/L阿托伐他汀对ox-LDL诱导的HUVEC分泌IL-18无影响(P>0.05),0.05,0.1,0.5,1.0 μmol/L阿托伐他汀能明显抑制oxLDL诱导的HUVEC分泌IL-18(P<0.05,P<0.01),抑制效应呈浓度依赖性.结论:阿托伐他汀呈剂量依赖性地抑制ox-LDL诱导的人HUVECs分泌IL-18,促进内皮细胞增殖,保护内皮功能,从而发挥他汀类药物调脂外抗动脉粥样硬化作用. 相似文献
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β-细辛醚对ox-LDL诱导的内皮细胞黏附分子表达的干预作用 总被引:7,自引:0,他引:7
目的 通过研究石菖蒲有效成份β-细辛醚对氧化低密度脂蛋白(ox-LDL)诱导的内皮细胞表面黏附分子表达的干预作用,探讨β-细辛醚抗动脉粥样硬化(AS)的作用及其机制。方法 采用流式细胞术和特异性标记单克隆抗体,测定内皮细胞表面细胞间黏附分子-1(ICAM-1,CD54)、血管细胞黏附分子-1(VCAM-1,CD106)、E-选择素(CD62E)和P-选择素(CD62P)的表达率。结果 ox-LDL诱导模型组VCAM-1、ICAM-1、CD62P、CD62E表达明显增高,与正常组比较有显著差异(P〈0.001),β-细辛醚及维生素C能降低内皮细胞表面黏附分子的表达,与模型组比较有统计意义(P 〈0.05-0.001)。结论 ox-LDL促进内皮细胞表面黏附分子表达,β-细辛醚对ox-LDL有明显的干预作用,能抑制ox-LDL诱导的内皮细胞表面黏附分子表达,有效地保护人内皮细胞免受ox-LDL所致毒性损伤。 相似文献
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目的观察小剂量阿托伐他汀抗动脉粥样硬化(AS)的作用。方法将Wistar大鼠48只,随机分为对照组(A组)、AS造模组(B组)、2.5及5mg.kg-.1d-1阿托伐他汀干预组(C组、D组),分别干预6、8、12周,为C1、C2、C3组及D1、D2、D3组,每组6只大鼠。A组喂食基础饲料;B、C、D组大鼠一次性腹腔注射60万U/kg维生素D3,后喂食高脂饲料8周。之后C、D各组按实验设计的剂量和疗程给予阿托伐他汀盐水灌胃。测定各组大鼠血脂水平;取主动脉弓组织行HE染色,观察动脉组织的病理改变,采用逆转录-聚合酶链反应检测细胞间黏附分子1(ICAM-1)、基质金属蛋白酶2(MMP-2)、基质金属蛋白酶组织抑制剂1(TIMP-1)表达情况。结果①血脂水平:2.5mg.kg-.1d-1干预组大鼠血脂水平无明显改善(均P>0.05);不同疗程5mg.kg-.1d-1干预组大鼠的血脂水平均有明显改善,且干预时间越长改善程度越明显(均P<0.05)。②形态学改变:B组大鼠动脉可见隆起于内膜表面的动脉粥样硬化斑块形成;不同剂量药物干预组大鼠的动脉仅见内膜增厚、血管平滑肌细胞增殖,均无明显斑块形成。且5mg.kg-.1d-1干预组大鼠动脉内膜较2.5mg.kg-.1d-1组大鼠略平坦。③炎性因子表达:B组大鼠的ICAM-1、MMP-2及TIMP-1的mRNA表达明显增高;不同疗程、不同剂量阿托伐他汀干预组大鼠的上述炎性指标较B组均明显降低(均P<0.05)。相同疗程间比较,较大剂量组上述炎性指标降低更明显(均P<0.05);而相同剂量组不同疗程间比较,上述炎性指标的降低程度随疗程的延长,差异无统计学意义(均P>0.05)。结论较大剂量阿托伐他汀能完全抑制大鼠血管壁的炎性反应,而较小剂量阿托伐他汀仅能部分抑制炎性反应;其抗炎作用与治疗时间无关。 相似文献
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目的 探讨细胞间黏附分子(ICAM-1)在动脉粥样硬化(AS)形成中的作用及桑葚提取物的影响.方法 新西兰纯种白兔30只,随机分为对照组6只(喂饲全谷物饲料) 和模型组6只(予高脂饮食喂养) ;桑葚组18只,分为低、中、高剂量组,分别给予1、5、10 g/kg桑葚提取液灌胃,1次/d.各组喂养8 w,于0 w、2 w、4 w、6 w、8 w末采血,测血浆胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白的水平.于8 w末采完血后处死兔,取胸主动脉和冠状动脉用免疫组化法检测胸主动脉、冠状动脉ICAM-1表达.结果 对照组血脂在实验前后无明显变化,而模型组血浆胆固醇、甘油三酯、低密度脂蛋白在2 w末时较实验前及对照组即已明显升高(P<0.01).免疫组化染色显示,对照组兔胸主动脉壁、冠状动脉壁ICAM-1呈阴性表达,而模型组ICAM-1内皮细胞表达显著增强,且斑块内和中膜平滑肌表达亦增强、表达范围较大.桑葚提取物三组动脉壁ICAM-1表达显示,桑葚低、中剂量组的表达有所减弱,而桑葚高剂量组呈明显的弱阳性表达.结论 ICAM-1参与了AS的形成和发展,桑葚提取物可抑制ICAM-1的表达,从而抑制AS的形成.同时高脂血症与ICAM-1的表达间可能为一种剂量正相关关系. 相似文献
10.
阿托伐他汀对小鼠实验性动脉粥样硬化病变形成的抑制作用 总被引:1,自引:0,他引:1
目的观察阿托伐他汀对载脂蛋白E基因缺陷(apoE-/-)小鼠实验性动脉粥样硬化(AS)病变形成及血管细胞黏附分子-1(VCAM-1)表达的影响,探讨阿托伐他汀抑制AS病变形成的可能机制。方法将apoE-/-小鼠随机分为3组:阿托伐他汀高、低剂量组、模型组(等量生理盐水),每组8只,给药第8周后全部处死。酶法检测血清脂质含量;比色法检测氧化指标一氧化氮(NO)、总抗氧化能力(TAC)及丙二醛(MDA);病理图像分析法测定主动脉AS斑块面积及其与管腔面积的比值;免疫组织化学染色方法测定主动脉壁VCAM-1表达。结果阿托伐他汀高、低剂量组与模型组apoE-/-小鼠比较显示:(1)阿托伐他汀(高、低剂量)可以显著降低总胆固醇、甘油三酯水平(P<0.01),升高高密度脂蛋白胆固醇水平(P<0.01);(2)明显增加血浆NO及TAC(P<0.01),减少MDA的生成(P<0.01);(3)阿托伐他汀可减少斑块面积与管腔面积比值(P<0.01);(4)阿托伐他汀可下调VCAM-1的表达(P<0.01)。结论阿托伐他汀可能通过调节apoE-/-小鼠血脂代谢、增强其抗氧化能力及下调主动脉壁VCAM-1表达,抑制apoE-/-小鼠AS病变形成的发展。 相似文献
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T helper cells contribute to the induction and maintenance of rheumatic inflammation through the secretion of cytokines. The analysis of Th1 cells expressing interferon-γ, Th17 cells expressing interleukin-17 and the newly described Th1+17 cells could give insight into the pathophysiological mechanisms of rheumatic diseases. This could lead to the development of novel, targeted therapeutic strategies. 相似文献
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COX—1和COX—2抑制剂与胃肠道疾病 总被引:1,自引:0,他引:1
COX(cyclo -oxygenase)有两种异构体 :COX -1和COX -2 ,阿斯匹林和其它NSAIDs既有消炎镇痛作用也有较多的副作用 ,主要是由于其抑制COX的非选择性 ,因而较少副作用的选择性COX抑制剂 (抑制COX异构体COX -2 )在近几年越来越受到人们重视 ,这些药物有meloxicam、nimesulin、celecoxib、etodolac、尼美舒利 (nimesulide)等。 COX -1产物的作用研究证明 ,经由环氧和酶 (COX -1)参与形成的内源性花生四烯酸、前列腺素的代谢产物被认为是胃粘膜… 相似文献
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Mohamed BM Feighery C Kelly J Coates C O'Shea U Barnes L Abuzakouk M 《Digestive diseases and sciences》2006,51(10):1862-1868
Gluten-sensitive enteropathy is characterized by small intestinal damage. The pathogenic mechanisms involved are not precisely
understood. There is recent interest in the possibility that matrix metalloproteinases might play a pathogenic role. Using
immunohistochemistry technique, we examined the protein expression of matrix metalloproteinases-1, -3, and -9 and the tissue
inhibitor metalloproteinase-1 in duodenal biopsies from 30 patients with celiac disease and dermatitis herpetiformis. We demonstrated
that the percentage of cells expressing these enzymes and their inhibitor in all patients was significantly greater than in
the normal controls (P < 0.0001). This was evident even in patients with a minimal lesion but was most marked in patients with severe damage, mirroring
the degree of inflammation in the small intestinal tissue. The increased expression of these enzymes and their inhibitor in
the duodenal mucosa of patients with gluten-sensitive enteropathy suggests a role for these enzymes in the tissue remodeling
which is a feature of these disorders. 相似文献
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Role of human cytochrome P450 1A1, 1A2, 1B1, and 3A4 in the 2-, 4-, and 16alpha-hydroxylation of 17beta-estradiol 总被引:8,自引:0,他引:8
The steady-state kinetics and specific activity of 2-, 4-, and 16alpha-hydroxylation of 17beta-estradiol (E(2)) were evaluated for human cytochrome P450 (CYP) 1A1, 1A2, 1B1, and 3A4 enzymes, using complementary DNA-expressed CYP isoforms. CYP1A2 showed the highest 2-hydroxylation activity, followed by CYP1A1, 1B1, and 3A4. CYP1B1 had the highest 4-hydroxylation activity, followed by CYP1A2, 1A1, and 3A4. The 16alpha-hydroxylation reaction was catalyzed mainly by CYP1A2 and, to a similar, slightly lower extent, CYP3A4 and 1A1, with a lesser contribution by CYP1B1. The E(2) 2-, 4-, and 16alpha-hydroxylation activities of human liver microsomes were 1.3 +/- 0.3, 0.5 +/- 0.06, and 0.3 +/- 0.05 nmol metabolite/min/nmol P450, respectively. The contribution of CYP1A1 and 1B1 (mainly extrahepatic) to the E(2) hydroxylation reactions, relative to CYP1A2 and 3A4 (predominantly hepatic), may be relevant to understanding the process of hormonal carcinogenesis both in liver and in extrahepatic tissues. 相似文献
17.
Dr. S. Ozen U. Saatci A. Bakkaloglu O. Ozdemir N. Besbas S. Kirazli S. Ozdemir 《Clinical rheumatology》1997,16(2):173-178
Summary The immunoinflammatory pathogenesis of juvenile chronic arthritis (JCA) involves the activation of many pathways including various cytokines. We have evaluated the levels of interleukin (IL)-1, IL-6 and IL-8 in 29 JCA patients. The age range was 1–16 with a mean of 10.1. A disease activity score was developed on the basis of: 1.constitutional symptoms and/or morning stiffness, 2.presence of joint swelling, 3.warmth, 4.limited range of motion, and 5.joint pain. This score correlated very significantly with laboratory disease activity markers such as erythrocyte sedimentation rate (ESR) and CRP (both p=0.006) and also correlated with IL-1 and IL-6 levels. The levels of IL-1 decreased in four of the five patients with improved disease activity. IL-6 but not IL-1 correlated significantly with the number of inflamed joints (p=0.013); IL-6 also strongly correlated with rheumatoid factor supporting this cytokine's role in B cell induction (p=0). Haemoglobin values correlated negatively with the activity index, ESR, CRP, IL-1 and IL-6. IL-8 did not correlate with disease activity markers. In the systemic patients all cytokines tended to be higher. Our data suggest that interleukins 1 and 6 are effective in the pathogenesis of JCA. Whether cytokines may be used for monitoring therapy may be clarified with further studies. 相似文献
18.
Although much is known about the expression insulin-like growth factors (IGF) and their receptors in the murine oviduct, significantly
less is known about the expression of IGF binding proteins (IGFBPs). To fill this gap in our knowledge, we identified and
characterized the tissue specific expression of IGFBP-1 to-6 in rat oviducts over the estrous cycle byin situ hybridization and immunocytochemistry. Tissues were analysed on proestrus (P1000 h, P2000 h), estrus (E0200, E1000 h), and
diestrus I and II (DI 1100 h, DII 1100 h). IGFBP-1 was undetectable in the oviduct over the cycle. IGFBP-2 was selectively
expressed in the luminal epithelium. The mRNA levels were high between P2000 h and E1000 h but low or undetectable thereafter.
Immunoreactive IGFBP-2 was strong to very strong in these cells over most of the cycle. IGFBP-3 mRNA was undetectable in the
oviduct; however, strong hybridization and immunoreactive signals were present in the mesosalpinx and mesotubarium, particularly
at DI and DII. IGFBP-4 mRNA was not detected in the oviduct. In contrast, immunoreactive IGFBP-4 was observed in the luminal
epithelium and the intensity was very strong after ovulation (E1000 h, DI and DII). IGFBP-5 and-6 mRNAs were selectively expressed
in circular smooth muscle cells. Hybridization signals were evident over the cycle, but were greatest at estrus. By comparison,
IGFBP-5 and-6 proteins were essentially undetectable in these cells except at DII 1100 h when immunostaining was moderate
to high. Luminal epithelial cells were weakly positive for IGFBP-5 and-6. However, intense immunostaining was associated with
the ciliated border and the luminal fluid juxtaposed to these cells during the cycle. The oocyte-cumulus complexes were immunostained
intensely for IGFBP-2,-4,-5 and-6, but their mRNAs were undetectable. The signals were strongest in degenerating cumulus cells
suggesting a potential role for these IGFBPs in cumulus apoptosis. These results demonstrate that the estrous cycle is accompanied
by major changes in the pattern of expression of IGFBP-2,-4,-5 and-6 in the rat oviduct. We therefore conclude that the regulated
production of these particular IGFBPs may be functionally important in modulating IGF activities in the oviduct, oocyte cumulus
complexes, and perhaps the preimplantation embryo as well. 相似文献
19.
Svingen PA Karp JE Krajewski S Mesner PW Gore SD Burke PJ Reed JC Lazebnik YA Kaufmann SH 《Blood》2000,96(12):3922-3931
Recent studies have suggested that variations in levels of caspases, a family of intracellular cysteine proteases, can profoundly affect the ability of cells to undergo apoptosis. In this study, immunoblotting was used to examine levels of apoptotic protease activating factor-1 (Apaf-1) and procaspases-2, -3, -7, -8, and -9 in bone marrow samples (at least 80% leukemia) harvested before chemotherapy from adults with newly diagnosed acute myelogenous leukemia (AML, 42 patients) and acute lymphocytic leukemia (ALL, 18 patients). Levels of each of these polypeptides varied over a more than 10-fold range between specimens. In AML samples, expression of procaspase-2 correlated with levels of Apaf-1 (R(s) = 0.52, P <.02), procaspase-3 (R(s) = 0.56, P <.006) and procaspase-8 (R(s) = 0.64, P <.002). In ALL samples, expression of procaspases-7 and -9 was highly correlated (R(s) = 0.90, P <.003). Levels of these polypeptides did not correlate with prognostic factors or response to induction chemotherapy. In further studies, 16 paired samples (13 AML, 3 ALL), the first harvested before induction therapy and the second harvested at the time of leukemia regrowth, were also examined. There were no systematic alterations in levels of Apaf-1 or procaspases at relapse compared with diagnosis. These results indicate that levels of initiator caspases vary widely among different leukemia specimens but cast doubt on the hypothesis that this variation is a major determinant of drug sensitivity for acute leukemia in the clinical setting. (Blood. 2000;96:3922-3931) 相似文献
20.