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Expression of inducible nitric oxide synthase and cyclooxygenase-2 in pancreatic adenocarcinoma:Correlation with microvessel density 被引量:14
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作者 Hans U.Kasper Hella Wolf +2 位作者 Uta Drebber Helmut K.Wolf Michael A.Kern 《World Journal of Gastroenterology》 SCIE CAS CSCD 2004年第13期1918-1922,共5页
AIM:Cydooxygenases (COX) are key enzymes for conversion of arachidonic acid to prostaglandins.Nitric oxide synthase (NOS) is the enzyme responsible for formation of nitric oxide. Both have constitutive and inducible i... AIM:Cydooxygenases (COX) are key enzymes for conversion of arachidonic acid to prostaglandins.Nitric oxide synthase (NOS) is the enzyme responsible for formation of nitric oxide. Both have constitutive and inducible isoforms.The inducible isoforms (iNOS and COX-2) are of great interest as regulators of tumor angiogenesis,tumorigenesis and inflammatory processes.This study was to clarify their role in pancreatic adenocarcinomas. METHODS:We investigated the immunohistochemical iNOS and COX-2 expression in 40 pancreatic ductal adenocardnomas of different grade and stage.The results were compared with microvessel density and dinicopathological data. RESULTS:Twenty-one (52.5%) of the cases showed iNOS expression,15 (37.5%) of the cases were positive for COX-2. The immunoreaction was heterogeneously distributed within the tumors.Staining intensity was different between the tumors.No correlation between iNOS and COX-2 expression was seen.There was no relationship with microvessel density. However,iNOS positive tumors developed more often distant metastases and the more malignant tumors showed a higher COX-2 expression.There was no correlation with other clinicopathological data. CONCLUSION:Approximately half of the cases expressed iNOS and COX-2.These two enzymes do not seem to be the key step in angiogenesis or carcinogenesis of pancreatic adenocarcinomas.Due to a low prevalence of COX-2 expression,chemoprevention of pancreatic carcinomas by COX-2 inhibitors can only achieve a limited success. 展开更多
关键词 Adenocarcinoma Aged Aged 80 and over cyclooxygenase 2 Female Humans Immunohistochemistry ISOENZYMES Male Membrane Proteins MICROCIRCULATION Middle Aged Nitric Oxide Synthase Nitric Oxide Synthase type II Pancreas Pancreatic Neoplasms Prostaglandin-Endoperoxide Synthases
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Effects of melatonin on the expression of iNOS and COX-2 in rat models of colitis 被引量:7
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作者 Wei-GuoDong QiaoMei +3 位作者 Jie-PingYu Jian-MingXu LiXiang YuXu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2003年第6期1307-1311,共5页
AIM: To investigate the effects of melatonin (MT) on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in rat models of colitis.METHODS: Healthy adult Sprague-Dawlay (SD) rats of bo... AIM: To investigate the effects of melatonin (MT) on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in rat models of colitis.METHODS: Healthy adult Sprague-Dawlay (SD) rats of both sexes, weighing 280±30 g, were employed in the present study. The rat models of colitis were induced by either acetic acid or 2,4,6-trinitrobenzene sulfonic acid (TNBS) enemas. The experimental animals were randomly divided into melatonin treatment and model control group that were intracolicly treated daily with melatonin at doses of 2.5, 5.0, 10.0 mg.kg-1 and equal amount of saline respectively from 24 h following induction of colitis in rats inflicted with acetic acid enema and the seventh day in rats with TNBS to the end of study. A normal control group of rats treated with neither acetic acid nor TNBS but saline enema was also included in the study. On the 28th day of the experiment, the rat colon mucosal damage index (CDMI) was calculated, and the colonic prostaglandin E2(PGE2), nitric oxide (NO), as well as the iNOS and COX-2expression were also determined biochemically or immunohistochemically.RESULTS: CDMI increased to 2.87±0.64 and 3.12±1.12respectively in rats treated with acetic acid and TNBS enema,which was in accordance with the significantly elevated colonic NO and PGE2 contents, as well as the up-regulated colonic iNOS and COX-2 expression in both of the two rat models of colitis. With treatment by melatonin at the doses of 5.0 and 10.0 mg@kg-1, CDMI in both models of rat colitis was significantly decreased (P<0.05-0.01), which accorded synchronously and unanimously with the reduced colonic NO and PGE2 content, as well as the down-regulated expression of colonic iNOS and COX-2.CONCLUSION: Melatonin has a protective effect on colonic injury induced by both acetic acid and TNBS enemas, which is probably via a mechanism of local inhibition of iNOS and COX-2 expression in colonic mucosa. 展开更多
关键词 Animals COLITIS Colon cyclooxygenase 2 Enzyme Inhibitors Intestinal Mucosa ISOENZYMES inhibitors MELATONIN Nitric Oxide Synthase Nitric Oxide Synthase type II Prostaglandin-Endoperoxide Synthases RATS Rats Sprague-Dawley
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葛根素对大鼠酒精性肝炎的影响及其机制 被引量:6
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作者 曲智威 温春阳 +4 位作者 王爱平 鞠文博 任爱华 刘卯阳 周艳 《世界华人消化杂志》 CAS 北大核心 2009年第7期657-661,共5页
目的:探讨葛根素对酒精性肝炎的作用机制.方法:21只Wistar大鼠,随机分为3组,正常对照组(n=7)用玉米油+500g/L葡萄糖20mL/(kg?d)灌胃,模型组(n=7)用400mL/L乙醇按8g/(kg?d)+玉米油灌胃,葛根素组(n=6):葛根素+酒精,按葛根素5mg/(kg?d)腹... 目的:探讨葛根素对酒精性肝炎的作用机制.方法:21只Wistar大鼠,随机分为3组,正常对照组(n=7)用玉米油+500g/L葡萄糖20mL/(kg?d)灌胃,模型组(n=7)用400mL/L乙醇按8g/(kg?d)+玉米油灌胃,葛根素组(n=6):葛根素+酒精,按葛根素5mg/(kg?d)腹腔注射给药.采用比色法测定血清AST,ALT及GST,放免法测定血浆PGE2,TNF及IL-6,Western blot方法检测肝组织COX-2表达,并通过光镜观察肝组织病理变化.结果:血浆ALT,AST及GST模型组与正常对照组比较有明显升高(107.5±6.81vs33.20±10.55,138.29±9.72vs47.86±14.3,3.57±0.53vs1.43±0.43,均P<0.01);与模型组比较,葛根素组血浆ALT及AST水平(52.33±13.19,63.33±7.03)有明显下降(P<0.01).GST有下降趋势,但无明显著意义;模型组与正常对照组比较血浆PGE2,TNF及IL-6明显上升(274.13±26.15vs193.84±23.97,1.85±0.11vs0.90±0.18,68.07±12.64vs40.50±5.09,均P<0.01);与模型组比较,葛根素组血浆PGE2,TNF及IL-6明显下降(227.05±21.55,1.35±0.19,53.16±5.62,均P<0.01),COX-2正常对照组呈弱表达,模型组显著高表达,与正常对照组比较差别显著(P<0.01),葛根素组COX-2表达下调,与模型组相比有明显下调(F=27.94,P<0.01).结论:葛根素通过抑制肝脏COX-2的表达,从而减少炎症介质PGE2、TNF及IL-6的生成,最终减轻酒精对肝脏的损伤作用. 展开更多
关键词 葛根素 酒精性肝炎 前列腺素2 肿瘤坏死 因子 白介素6 环氧化物酶2
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冠状动脉粥样硬化组织环氧化物酶-2、诱导型前列腺素合成酶-1表达及塞来昔布的影响 被引量:2
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作者 李新华 刘恒方 +1 位作者 杨期东 苗旺 《中国心血管杂志》 2007年第3期175-177,181,共4页
目的探讨兔冠状动脉粥样硬化组织环氧化物酶-2(Cox-2)、诱导型前列腺素合成酶-1(mPGES-1)表达机制及塞来昔布对其表达的影响。方法采用32只雄性新西兰大白兔,正常对照组8只(A 组);另24只将给予1%高胆固醇喂养2周,建立兔动脉粥样硬化动... 目的探讨兔冠状动脉粥样硬化组织环氧化物酶-2(Cox-2)、诱导型前列腺素合成酶-1(mPGES-1)表达机制及塞来昔布对其表达的影响。方法采用32只雄性新西兰大白兔,正常对照组8只(A 组);另24只将给予1%高胆固醇喂养2周,建立兔动脉粥样硬化动物模型。将模型兔随机分为无干预组(B 组)、小剂量塞来昔布治疗组(15mg/kg,C 组),大剂量塞来昔布治疗组(35 mg/kg,D 组),每组8只。治疗4周后取双侧冠状动脉并分为平等2段,分别行半定量逆转录聚合酶链反应(RT-PCR)及蛋白印记法(Western blot)测定各组冠状动脉粥样硬化组织 Cox-2及 mPGES-1表达。结果与 A 组比较,B 组冠状动脉粥样硬化组织 Cox-2及 mPGES-1表达增高,差异具有统计学意义(P<0.05);与 B 组比较,C、D 组冠状动脉组织的 Cox-2及 mPGE-1表达明显下调,差异有统计学意义(P<0.05);与 B 组比较,C 组的 ALD 明显升高,差异有统计学意义(P<0.05)。结论在动脉粥样硬化的病理过程中炎症反应可能起着主导作用,塞来昔布干预可抑制 Cox-2及 mPGES-1表达,减缓动脉粥样硬化的进展。 展开更多
关键词 塞来昔布 动脉粥样硬化 环氧化物酶-2 诱导型前列腺素合成酶-1
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兔动脉粥样硬化组织COX-2、mPGES-1表达及阿伐他汀的影响 被引量:1
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作者 王彦 施雪青 +2 位作者 曲振运 王冬梅 赵赫男 《第三军医大学学报》 CAS CSCD 北大核心 2012年第7期643-646,共4页
目的通过观察环氧化酶Ⅱ(cyclooxygenase-2,COX-2)、诱导型前列腺素合成酶Ⅰ(membrane associatedprostaglandin E-1,mPGES-1)在兔动脉粥样硬化(AS)斑块中的表达水平及阿伐他汀对其的干预作用。方法取40只体质量为2.0~2.2 kg的3月龄健... 目的通过观察环氧化酶Ⅱ(cyclooxygenase-2,COX-2)、诱导型前列腺素合成酶Ⅰ(membrane associatedprostaglandin E-1,mPGES-1)在兔动脉粥样硬化(AS)斑块中的表达水平及阿伐他汀对其的干预作用。方法取40只体质量为2.0~2.2 kg的3月龄健康雄性新西兰兔,随机分为正常对照组8只(普通饲料);高脂模型组32只(高胆固醇饲料)。8周后将高脂模型组再分为模型组、阿伐他汀治疗Ⅰ组、Ⅱ组及Ⅲ组[剂量分别为2.5、5及10 mg/(kg.d),n=8]。6周后取各组兔冠状动脉,检测其COX-2及mPGES-1的表达;同时,采血检测各组血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)及极低密度脂蛋白胆固醇(VLDL-C)浓度。结果模型组血清TC、TG、HDL-C、LDL-C及VLDL-C水平与正常对照组比较差异显著(P<0.05);而阿伐他汀治疗Ⅱ组及Ⅲ组上述各项指标与模型组比较差异显著(P<0.05);阿伐他汀治疗Ⅰ组各项血脂水平较之模型组无显著差异(P>0.05)。与正常对照组比较,模型组动脉粥样硬化组织的COX-2及mPGES-1表达显著增高(P<0.05);与模型组比较,治疗Ⅱ组、Ⅲ组动脉粥样硬化组织的COX-2及mPGES-1表达明显下调(P<0.05)。结论阿伐他汀可能通过降低COX-2/mPGES-1表达、降低血脂,进而发挥其对AS的治疗作用。 展开更多
关键词 动脉粥样硬化 环氧化酶-2 诱导型前列腺素合酶-1 阿伐他汀
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氧化型低密度脂蛋白对血管平滑肌细胞环氧化物酶-2表达的影响
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作者 胡惠华 王琳 +3 位作者 刘恒方 苗旺 刘尊敬 杨期东 《中国实用神经疾病杂志》 2008年第4期23-25,共3页
目的探讨氧化型低密度脂蛋白对血管平滑肌细胞(VSMC)环氧化物酶-2(COX-2)表达的影响。方法采用氧化型低密度脂蛋白(ox-LDL)诱导形成的平滑肌源性泡沫细胞模型,RT-PCR及Western印迹法观察不同浓度和时间点的ox-LDL处理对细胞COX-2表达的... 目的探讨氧化型低密度脂蛋白对血管平滑肌细胞(VSMC)环氧化物酶-2(COX-2)表达的影响。方法采用氧化型低密度脂蛋白(ox-LDL)诱导形成的平滑肌源性泡沫细胞模型,RT-PCR及Western印迹法观察不同浓度和时间点的ox-LDL处理对细胞COX-2表达的影响。结果12.5、25、501、00 mg/L四种不同浓度的ox-LDL与VSMC共同孵育24 h4、8 h、96 h后均可使VSMC COX-2表达上调(P<0.05),且浓度越高,上调越显著,在24 h的时间点开始显著上调,96 h达高峰。结论在ox-LDL诱导体外培养的血管平滑肌细胞形成泡沫细胞的过程中,存在COX-2的表达上调,可能与平滑肌源性泡沫细胞炎性反应有关。 展开更多
关键词 环氧化物酶 泡沫细胞 氧化型低密度脂蛋白 血管平滑肌细胞
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Extract of buckwheat sprouts scavenges oxidation and inhibits pro-inflammatory mediators in lipopolysaccharide-stimulated macrophages (RAW264.7) 被引量:17
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作者 Rajendra Karki Cheol-Ho Park Dong-Wook Kim 《Journal of Integrative Medicine》 SCIE CAS CSCD 2013年第4期246-252,共7页
OBJECTIVE: Buckwheat has been considered as a potential source of nutraceutical components on the world market of probiotic foodstuffs. The purpose of this study was to evaluate the effects of tartary buckwheat (Fag... OBJECTIVE: Buckwheat has been considered as a potential source of nutraceutical components on the world market of probiotic foodstuffs. The purpose of this study was to evaluate the effects of tartary buckwheat (Fagopyrum tataricum) sprouts on oxidation and pro-inflammatory mediators. METHODS: The anti-oxidant effects of buckwheat extract (BWE) and rutin were evaluated by using 1,1-diphenyl-2-picrylhydrazyl (DPPH)-and nitric oxide (NO)-scavenging activities, serum peroxidation and chelating assays. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells were used to evaluate anti-inflammatory activities of buckwheat and rutin. NO production in LPS- stimulated RAW264.7 cells was determined by using Griess reagent. The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-κB) p65 subunit in cytosolic and nuclear portions were determined by Western blot analysis. Also, the production of inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was determined by enzyme-linked immunosorbent assay. RESULTS: Inhibitory concentration 50 values for DPPH- and NO-scavenging activities of BWE were 24.97 and 72.54 μg/mL respectively. BWE inhibited serum oxidation and possessed chelating activity. Furthermore, BWE inhibited IL-6 and TNF-a production in LPS-stimulated RAW264.7 cells. Also, BWE inhibited iNOS and COX-2 expression and NF-KB p65 translocation. CONCLUSION: Buckwheat sprouts possessed strong antioxidant activity and inhibited production of pro-inflammatory mediators in the applied model systems. Thus, buckwheat can be suggested to be beneficial in inflammatory diseases by inhibiting the free radicals and inflammatory mediators. 展开更多
关键词 FAGOPYRUM plant extracts OXIDATION nitric oxide synthase type II cyclooxygenase 2
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食管黏膜环氧化酶-2和同源型盒转录因子2与食管癌贲门癌术后胃食管返流变化的关系 被引量:5
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作者 黎仕兴 《海南医学》 CAS 2014年第2期183-185,共3页
目的探讨食管癌贲门癌术后胃管或食管返流与食管黏膜换氧化酶-2(COX-2)和同源型盒转录因子2(CDX2)表达的相关性。方法术后分别于不同时间段对35例食管癌和贲门癌患者进行全天氢离子浓度指数(pH)和胆红素监测,另外进行电子胃镜,免疫组织... 目的探讨食管癌贲门癌术后胃管或食管返流与食管黏膜换氧化酶-2(COX-2)和同源型盒转录因子2(CDX2)表达的相关性。方法术后分别于不同时间段对35例食管癌和贲门癌患者进行全天氢离子浓度指数(pH)和胆红素监测,另外进行电子胃镜,免疫组织学检查,分析COX-2和CDX2的检测结果,针对胃食管返流患者,采用仪器测量的方式,通过计算得出分数(DeMeester评分)。结果术后返流性食管炎发生率及DeMeester评分随时间延长逐渐升高(P<0.05)。COX-2、CDX2在正常食管黏膜基底细胞内不表达或呈弱阳性表达;术后参与食管黏膜呈阳性表达。Barrett食管化生上皮细胞胞浆内的COX-2、CDX2表达水平呈强阳性。残余食管黏膜发生返流性食管炎的患者CDX2水平显著高于未发生食管炎者,有无发生返流性食管炎的患者COX-2的表达水平差异无统计学意义(P>0.05)。结论食管癌贲门癌术后酸返流同返流性食管炎的发生率随着时间的延长而增加;食管黏膜上的COX-2、CDX2表达是胃食管返流发生的早期变化,同时二者持续呈阳性表达可以作为胃食管返流发生的分子标记,为临床治疗提供参考。 展开更多
关键词 食管癌 贲门癌 食管黏膜 环氧化酶-2 (COX-2) 同源型盒转录因子2(CDX2)
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5-脂加氧酶在胃癌中的表达与环氧化酶-2和甲酰肽受体2的关系及其临床意义
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作者 李庆 徐芬 +2 位作者 雷浪 李里香 郝华 《外科研究与新技术》 2022年第4期232-237,共6页
目的 探讨5-脂加氧酶(5-LOX)在胃癌中的表达与5-LOX与环氧化酶-2(COX-2)和甲酰肽受体2(FPR_(2))的关系及其临床意义。方法 采用免疫组织化学法检测70例胃癌组织中3个指标的表达情况,并分析三者间的关系以及临床病理联系。沉默5-LOX基因... 目的 探讨5-脂加氧酶(5-LOX)在胃癌中的表达与5-LOX与环氧化酶-2(COX-2)和甲酰肽受体2(FPR_(2))的关系及其临床意义。方法 采用免疫组织化学法检测70例胃癌组织中3个指标的表达情况,并分析三者间的关系以及临床病理联系。沉默5-LOX基因观察对COX-2及FPR_(2)的表达有无影响。结果 ≤45岁和>45岁患者5-LOX阳性表达率分别为76.0%和84.4%;肿块直径≤3 cm和>3 cm者阳性表达率分别为82.1%和81.0%;低分化腺癌、中-高分化腺癌和黏液腺癌阳性表达率分别为80.0%、80.0%和90.0%,组间差异均无统计学意义(P>0.05)。在无、有淋巴结转移组中5-LOX阳性率分别为71.8%和93.5%;在Ⅰ~Ⅱ、Ⅲ~Ⅳ期胃癌中5-LOX的阳性表达率分别为75.0%和95.5%,组间差异均有统计学意义(P<0.05);5-LOX在COX-2阳性和阴性病例中阳性率分别为81.6%和81.0%,组间差异无统计学意义(P>0.05);5-LOX在FPR_(2)阳性和阴性病例中阳性率分别为78.1%和84.2%,组间差异无统计学意义(P>0.05)。在SGC-7901转染实验中,沉默5-LOX基因对COX-2及FPR_(2)的表达没有影响。结论 5-LOX在胃癌的侵袭、转移过程中起重要作用,同时靶向5-LOX和COX-2有望成为治疗胃癌的有效手段。 展开更多
关键词 胃癌 5-脂加氧酶 环氧化酶-2 甲酰肽受体2
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流式细胞术测定COX-2,iNOS基因蛋白在食管癌上的表达及其与Bcl-2,PCNA的相关性
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作者 杜芸 王小玲 +3 位作者 王永军 吴国祥 杨会钗 左连富 《癌变.畸变.突变》 CAS CSCD 2005年第4期224-226,共3页
背景与目的:研究环氧化酶-2(Cyclooxygenase2,COX-2),Ⅱ型一氧化氮合酶(TypeⅡnitricoxidesynthase,iNOS)基因蛋白在食管鳞癌上的表达及与食管癌的分化和淋巴结转移的关系,并探讨其与PCNA、Bcl-2的相关性。材料与方法:采用流式细胞术定... 背景与目的:研究环氧化酶-2(Cyclooxygenase2,COX-2),Ⅱ型一氧化氮合酶(TypeⅡnitricoxidesynthase,iNOS)基因蛋白在食管鳞癌上的表达及与食管癌的分化和淋巴结转移的关系,并探讨其与PCNA、Bcl-2的相关性。材料与方法:采用流式细胞术定量检测65例食管鳞状细胞癌上增殖细胞核抗原、iNOS、PCNA(Proliferatingcellnuclearantien)及Bcl-2基因的蛋白表达量(用荧光指数FI表示)。结果:COX-2,iNOS在低分化型(Ⅲ级)鳞癌上的表达量明显高于分化型(Ⅰ、Ⅱ级)鳞癌(其P值分别为0.0001,0.0385);二者之间差异有显著性。该两种基因蛋白的表达强弱均与淋巴结转移无关。COX-2与PCNA、Bcl-2呈明显正相关,而iNOS与PCNA、Bcl-2无明显相关性。结论:COX-2,iNOS的表达强弱与食管癌的分化密切相关,二者在促食管癌的发生发展上可能有互相协同作用;COX-2可能促进食管癌细胞的增殖,并通过刺激Bcl-2蛋白表达抑制凋亡。 展开更多
关键词 食管癌 环氧化酶-2 Ⅱ型一氧化氮合酶 增殖细胞核抗原 BCL-2
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