反流性食管炎患者一氧化氮、超氧化物歧化酶检测及意义

目的探讨一氧化氮（NO）、超氧化物歧化酶（SOD）在反流性食管炎（RE）患者发病中的作用。方法选择反流性食管炎患者50例作为RE组，慢性胃炎患者30例作为对照组。采用NADPH-d酶组化染色法对RE和对照组食管黏膜组织中的一氧化氮合酶（NOS）进行定性检验，应用硝酸还原法和黄嘌呤氧化酶法分别测定血中及食管组织中的NO和SOD含量。结果RE组患者食管黏膜大多呈NOS阳性反应，阳性率明显高于对照组（P〈0．01），RE组患者食管黏膜组织及血清NO含量也明显高于对照组（P〈0．01），而RE组患者食管黏膜组织及血清的SOD含量明显低于对照组（P〈0．01）。不同程度RE食管组织的NO含量与SOD含量具有一定的相关性（r=-0．645，P〈0．01）。结论NO、SOD在RE患者的发病中可能共同发挥着重要的作用。     

旋覆代赭汤对反流性食管炎模型大鼠白细胞介素-6及肿瘤坏死因子-α的影响

[目的]观察旋覆代赭汤对混合性反流性食管炎（RE）模型大鼠血浆及食管组织细胞因子白细胞介素（IL）-6及肿瘤坏死因子（TNF）-α水平的影响,揭示RE的关键病机及深入研究旋覆代赭汤治疗RE的作用机制。[方法]采用“食管十二指肠端侧吻合术”制作动物模型,大鼠随机分为正常对照组、假手术组、模型组、西药莫沙必利对照组（西药组）、旋覆代赭汤治疗组（中药组）。各组给予相应处理或用药后,通过ELISA的方法分别检测各组血浆及食管组织中细胞因子IL-6及TNF-α水平变化。[结果]中药组及西药组较模型组能明显降低RE模型大鼠食管组织中IL-6及TNF-α水平（P〈0．05）,中药组与西药组相比IL-6及TNF-α水平降低（P〈0．05）;而血浆中IL-6含量结果表明,中药组与西药组比较,差异无统计学意义（P〉0．05）,其余结果与食管组织结果一致。[结论]旋覆代赭汤可显著降低RE模型大鼠食管组织中IL-6及TNF-α水平,表明其对改善食管局部及外周炎症反应、改善食管下端括约肌的松弛情况等有显著效果。     

复方白及糊对反流性食管炎模型大鼠黏膜血流的影响

[目的]探讨复方白及糊治疗反流性食管炎（RE）的作用机制。[方法]实验大鼠随机分为4组,各23只。甲、乙、丙3组均采用改良部分贲门肌切开加外置幽门部分结扎术,制备RE大鼠模型,并与假手术组对照。甲组造模前7天起,每天灌食复方白及糊3ml;造模后与乙组一起每天灌食等量复方白及糊,丙组同时灌等量0.85%氯化钠。分别于术后7、14d观察各组大鼠食管下段pH值、大体标本及组织学改变,同时进行食管黏膜血流量的测定。[结果]造模成功,造模大鼠食管黏膜血流均有所下降,甲、乙组可使模型大鼠食管下段pH升高,损伤黏膜迅速修复,食管下端黏膜血流增加,其中甲组作用更强,与丙组、假手术组比较差异有统计学意义（P〈0.05）。[结论]复方白及糊治疗RE,可能是通过抑酸,改善局部黏膜血供,加强食管黏膜上皮屏障实现的。     

非糜烂性反流病与反流性食管炎症状及食管酸暴露情况

目的比较非糜烂性反流病（NERD）与反流性食管炎（RE）的临床症状及食管酸暴露情况。方法具有反流症状的患者155例,进行胃镜检查和食管24hpH动态监测。结果155例患者中诊断RE76例（49．0％）,其中A、B、C、D级分别为40、24、8和4例;诊断NERD79例（51．0％）;RE组中pH监测阳性57例（75．0％）,NERD组26例（32．9％）,差异有统计学意义（P〈0．05）;NERD组食管外症状发生率较RE组高,差异有统计学意义（P〈0．05）,而典型的反流症状发生率两组比较差异无统计学意义（P〉0．05）;RE组各项酸反流指标均大于NERD组,差异有统计学意义（P〈0．05）;轻度RE（LA-A）组各项酸反流指标低于中度RE（LA—B）和重度RE（LA—C＋D）,差异有统计学意义（P〈0．05）,但中度RE（LA—B）与重度RE（LA—C＋D）之间的差异无统计学意义（P〉0．05）;79例NERD中,依据监测当日症状计算SI值,pH阴性sI阳性（NERDpH^-SI^＋）15例,pH阴性sI阴性（NERDpH^-SI^-）28例,NERDpH^-SI^＋组的pH〈4．0（％）和酸反流次数明显高于NERDpH^-SI^-组,差异有统计学意义（P〈0．05）。结论胃酸反流是RE形成的重要因素,其中胃酸的浓度及长反流与食管黏膜接触的次数是直接造成食管黏膜损伤的重要因素;酸反流的程度与RE的严重程度之间可能相关;NERD根据酸反流与症状的关系可分为不同的亚型,病理性酸反流所占比例相对较低,酸反流的强弱在其发病机制中可能未起到决定性作用。     

反流性食管炎和非糜烂性反流病患者症状谱、生活质量和精神心理状态调查

背景：胃食管反流病（GERD）包括非糜烂性反流病（NERD）、反流性食管炎（RE）和Barrett食管（BE），其发病机制可能有所不同。目的：分析比较NERD和RE患者的人口学特征和临床特点，为探讨其发病机制和有效治疗提供依据。方法：对连续入组的278例GERD患者进行问卷调查，内容包括一般人口学资料、胃食管反流以及相关症状评分、食管外症状、重叠症状、生活质量评价和精神心理状态评价。结果：NERD和RE分别占GERD的60．8％和37．1％；与RE组相比，NERD患者以女性多见（P〈0．05），平均年龄较轻（R〈0．05）。胃食管反流症状评分在两组患者间无显著差异，但RE组烧心频率较NERD组高（P〈0．05），而NERD组胸骨后疼痛更突出，反食症状较轻。两组患者的食管外症状、重叠症状发生率无显著差异。NERD组患者生活质量下降更明显。NERD组患者合并精神心理异常的比例显著高于RE组（P〈0．05），且抑郁评分高。结论：本组资料中大部分GERD患者为NERD，NERD和RE的反流以及相关症状谱无显著差异。但NERD患者常合并精神心理异常、生活质量下降，提示精神心理因素在NERD的发病中可能起重要作用。     

Cdx2和MUC2在反流性食管炎、Barrett食管和食管腺癌中的表达

目的研究Cdx2和MUC2在反流性食管炎、Barrett食管和食管腺癌中表达，探讨3种食管黏膜疾病的内在关系。方法选取反流性食管炎30例、Barrett食管18例及食管腺癌25例作为研究对象，以正常食管上皮黏膜25例作为对照，采用免疫组化方法检测Cdx2和MUC2的表达，对结果进行统计分析。结果Cdx2和MUC2在反流性食管炎、Barrett食管及食管腺癌中的蛋白阳性表达率均较正常对照组明显增高（P〈0．05）。Cdx2在正常食管黏膜上皮中无表达，在反流性食管炎、Barrett食管及食管腺癌中的阳性表达率分别为26．7％、66．7％和28．0％，在Barrett食管中表达明显高于反流性食管炎（P〈0．05），亦明显高于食管腺癌（P〈0．05）；MUC2在正常食管黏膜上皮和反流性食管炎组织无表达，在Barrett食管及食管腺癌中的阳性表达率分别为61．1％和24．0％，Barrett食管中表达率明显高于食管腺癌（P〈0．05）。两者表达情况相似。结论Cdx2是肠上皮化生的始动因素，MUC2的表达是肠上皮化生的晚发事件。Cdx2和MUC2在反流性食管炎、Barrett食管和食管腺癌组织中的表达情况支持这3种食管黏膜疾病间有密切的关系。     

铝碳酸镁对反流性食管炎食道粘膜保护机制的实验研究

目的：观察铝碳酸镁对急性反流性食道炎的防治作用，并探讨其作用机制。方法：采用十二指肠结扎复制反流性食管炎模型，光镜下和电镜下观察大鼠食管粘膜组织学表现，并计算粘膜损伤指数，激光多普勒血流计测定粘膜血流量，收集胃内潴留物测定PH值及总胆酸浓度。结果：光镜下模型组大型食管粘膜充血水肿，表面明显的炎性渗出，严重者出现粘膜细胞的变性坏死脱落，形成典型的溃疡结构。治疗组大鼠部分食管粘膜下层出现炎性细胞浸润，局部表层粘膜上皮脱落形成糜烂灶。电镜下治疗组大鼠血管炎症反应较模型组轻，上皮细胞连接与对照组相比的正常。模型组大鼠粘膜血流量较治疗组明显降低，其差异具有显著意义（P＜0．05），模型组大鼠胃潴留液量及PH值、粘膜损伤指数、总胆酸含量均较治疗组升高，两组相比差异具有显著意义（P＜0．05）。结论：除十二指肠反流的内容物内胆酸升高外，局部粘膜血流量降低、胃潴留液PH值改变亦参与了反流性食管炎的形成。铝碳酸镁通过与胆酸结合，改善局部粘膜血流状态及调节胃内PH值而发挥其粘膜保护作用。     

反流性食管炎85例酸及胆汁反流的同步监测

目的：研究反流性食管炎（RE）患者酸和胆汁反流的发生情况。方法：RE患者85例及健康志愿者20例,应用DigitraperMKⅢ型便携式pH监测仪及Bilitec 2000便携式胆汁监测仪同步监测食管24h pH变化及胆汁反流。结果：RE组有酸和胆汁共同反流者为53例（62．4％）,单纯酸反流者26例（30．6％）,单纯胆汁反流者3例（3．5％）,无任何反流者3例（3．5％）。RE组中酸及胆汁反流次数、持续反流大于5min次数、最长持续反流时间及反流总时间百分比均明显高于对照组（P＜0．01）。结论：胆汁反流与酸反流同样常见于RE患者,在胃食管反流病的发生中起重要作用,同步动态监测食管pH值及胆汁变化对RE的诊断有重要意义。     

滑动型食管裂孔疝患者食管24h pH、LES以及食管运动功能的研究

目的：探讨滑动型食管裂孔疝（HH）伴反流性食管炎（RE）和单纯反流性食管炎患者的食管动力学改变。方法：胃镜或上消化道钡餐确诊GERD患者62例，分为RE组32例和HH组30例，在X线透视下观察食管形态学、蠕动以及反流与廓清方式，同时监测食管24h pH和下食管括约肌（LES）压力及其松弛度，以及干、湿咽时食管蠕动的情况。结果：30例HH患者X线透视下均有食管粘膜增粗，头高脚低位下伴有食管钡剂反流现象，反流以抽吸型为主（80％），廓清以被动廓清为主，（36．67％）。LES静息压力为显著低于对照组（P＜0．05）；24h食管pH监测中总的卧位和立位反流时间百分比均显著低于对照组（P＜0．01），LES的长度各组间无明显差异。松弛率为33．33％，食管体部蠕动频率、波幅均较对照组低，间期明显延长。顺行性蠕动百分比较对照组明显降低（P＜0．05）。结论：HH可能是长期RE的结果，RE在HH发病中起重要的作用。     

小檗碱对非甾体消炎药相关性肠损伤的保护作用及其机制研究

背景：近年非甾体消炎药（NSAIDs）相关性肠损伤的发生率明显升高,但目前尚缺乏有效防治NSAIDs相关性肠损伤的药物。目的：研究中药小檗碱对NSAIDs相关性肠损伤的治疗作用及其机制。方法：将40只大鼠随机分为对照组、模型组以及低、中、高剂量小檗碱干预组（分别为25、50、75mg·kg-1·d-1）。采用7.5mg·kg-1·d-1双氯芬酸制备NSAIDs相关性肠损伤模型。造模第5d处死所有大鼠,行小肠黏膜大体、组织学评分。以ELISA法检测小肠黏膜前列腺素（PG）E2含量,硝酸还原酶法检测小肠黏膜和血清NO含量,免疫组化法检测小肠黏膜环氧合酶（COX）-1、COX-2表达。结果：与对照组相比,模型组大鼠小肠大体评分和组织学评分明显升高（P〈0．05）,小肠黏膜PGE,含量明显降低（P〈0．05）,小肠黏膜和血清NO含量明显升高（P〈0．05）,小肠黏膜COX-1表达明显降低（P〈0．05）,COX-2表达明显升高（P〈0．05）。给予低、中、高剂量小檗碱干预后,上述指标明显改善（P〈0．05）。结论：小檗碱对NSAIDs相关性肠损伤具有保护作用,其机制可能与小檗碱致小肠黏膜PGE：、COX-1表达升高以及组织和血清NO含量、COX-2表达降低有关。     

Effects of bile acids on cyclooxygenase-2 expression in a rat model of duodenoesophageal anastomosis

AIM:To examine the expression of cyclooxygenase-2(COX-2)and prostaglandin E2(PGE2)in rat esophageal lesions induced by reflux of duodenal contents.METHODS:Thirty 8-week-old male Wistar rats were exposed to duodenal content esophageal reflux.All animals underwent an esophagoduodenal anastomosis(EDA)with total gastrectomy to elicit chronic esophagitis.In ten rats sham operations with only a midline laparotomy were performed(Control).The rats were sacrificed at the 40th week,their esophagi were taken for hematoxylin and eosin staining and for examination of expression of COX2,PGE2,and proliferating cell nuclear antigen(PCNA),and total bile acids in the esophageal lumen was measured.RESULTS:After 40 wk of reflux,columnar dysplasia,squamous cell carcinoma and adenocarcinoma were observed.Total bile acids in the esophageal lumen were significantly increased in the EDA group compared with the sham operated rats.PCNA labelling index and esophageal tissue PGE2 levels were higher in dysplastic and cancer tissues than in control tissues.Overexpression of COX2 was observed in dysplastic and cancer tissues.CONCLUSION:Reflux of duodenal contents induces COX2 expression and increases prostaglandin synthesis in dysplastic and cancer tissues.This result suggests a possible mechanism by which bile acids promote esophageal cancer.     

环氧合酶-2在Barrett食管及其相关疾病中的表达及意义

目的研究环氧合酶(COX)-2在Barrett食管(BE)及其相关疾病中的表达情况及其意义。方法应用免疫组化S-P法分别测定59例BE,5例食管腺癌,5例重度反流性食管炎(RE)患者,10例食管黏膜正常者组织中COX-2的表达情况。数据采用等级分组秩和检验。结果COX-2在BE中的阳性率为86.4%.在食管腺癌中为5/5例,与正常食管(3/10例)和RE(2/5例)比较差异均有统计学意义(P<0.05)。长段BE黏膜中COX-2表达(100.0%)较短段BE(80.9%)高(P<0.05)。不同类型BE (全周型、舌型和岛型)、不同程度肠化生(轻度、中度、重度)COX-2的表达差异均无统计学意义(P> 0.05)。结论COX-2在BE和腺癌组织中的表达显著增高,长段BE黏膜中COX-2的表达较短段BE为高。     

IL-18BP和IL-4共表达腺病毒基因对关节炎小鼠滑膜组织COX-2和iNOS表达的作用

目的 本研究构建了共表达小鼠白细胞介素-18结合蛋白(IL-18BP)和IL-4的重组腺病毒载体(Ad mIL-18BP/mIL-4),将其用于胶原诱导型关节炎(CIA)小鼠局部关节基因治疗,以探讨对小鼠滑膜组织环氧化酶-2(COX-2)和诱导型一氧化氮合酶(iNOS)及其诱导产物前列腺素E2(PGE2)、一氧化氮(NO)表达水平的影响.方法 采用雄性的DBA-1/BOM小鼠,建立CIA的小鼠模型,经共表达小鼠IL-18BP和IL-4的重组腺病毒载体局部关节基因治疗后,分别采用半定量反转录一聚合酶链反应(RT-PCR)法和Westem印迹法检测滑膜组织COX-2、iNOS mRNA的表达水平和蛋白表达水平,用竞争ELISA和硝酸酶还原法检测关节滑膜液PGE2和NO的含量,并设AdLacZ组和磷酸盐缓冲液(PBS)组分别为病毒对照组和组织对照组.结果 AdmIL-18BP/mIL-4治疗组滑膜组织COX-2、iNOS mRNA表达水平明显低于AdLacZ对照组(0.15 vs 0.42,P<0.01;0.05 vs 0.77,P<0.01)和PBS对照组(0.15 vs 0.65,P<0.01;0.05 vs 0.64,P<0.01);AdmIL-18BP/mIL-4治疗组滑膜组织COX-2、iNOS的蛋白表达水平明显低于AdLacZ对照组(0.08 VS 0.92,P<0.01;0.11 vs 1.00,P<0.01)及PBS对照组(0.08 vs 0.77,P<0.01;0.11 vs 0.84,P<0.01);AdmIL-18BP/mIL-4治疗组关节滑膜液中PGE2及NO水平明显低于AdLacZ对照组[(0.68±0.06)vs(2.58±0.21)ng/ml,P<0.01;(23.4±2.5)vs(60.0±11.3) μmol/L,P<0.01]和PBS对照组[(0.68±0.06)vs(2.57±0.20)ng/mL,P<0.01;(23.4±2.5)vs(60.3±13.4)μmol/L,P<0.01].结论 共表达小鼠IL-18BP和IL-4的重组腺病毒基因治疗能明显下调COX-2和iNOS的表达水平,减少其诱导产物PGE2、NO的合成,这将为RA的基因治疗提供新的治疗策略.     

Expression of Bcl-2 and NF-κB in brain tissue after acute renal ischemia-reperfusion in rats

Objective:To investigate the effect of acute renal ischemia reperfusion on brain tissue.Methods:Fourty eight rats were randomly divided into four groups(n=12):sham operation group,30 min ischemia 60 min reperfusion group,60 min ischemia 60 min reperfusion group,and120 min ischemia 60 min reperfusion group.The brain tissues were taken after the experiment.TUNEL assay was used to detect the brain cell apoptosis,and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors.Results:Renal ischemiareperiusion induced apoptosis of brain tissues,and the apoptosis increased with prolongation of ischemia time.The detection at the molecular level showed decreased Bcl-2 expression,increased Bax expression,upreguiated expression of NF- κB and its downstream factor COX-2/PGE2.Conclusions:Acute renal ischemia-reperfusion can cause brain tissue damage,manifested as induced brain tissues apoptosis and inflammation activation.     

Anti-Helicobacterpylori therapy followed by celecoxib on progression of gastric precancerous lesions

AIM： To evaluate whether celecoxib, a selective cyclooxygenase 2 （COX-2） inhibitor, could reduce the severity of gastric precancerous lesions following Hel/cobacter pylori （H pylorl） eradication. METHODS： H pylori-eradicated patients with gastric precancerous lesions randomly received either celecoxib （n = 30） or placebo （n = 30） for up to 3 mo. COX-2 expression and activity was determined by immunostaining and prostaglandin E2 （PGE2） assay, cell proliferation by Ki-67 immunostaining, apoptosis by TUNEL staining and angiogenesis by microvascular density （MVD） assay using CD31 staining.RESULTS： COX-2 protein expression was significantly increased in gastric precancerous lesions （atrophy, intestinal metaplasia and dysplasia, respectively） compared with chronic gastritis, and was concomitant with an increase in cell proliferation and angiogenesis. A significant improvement in precancerous lesions was observed in patients who received celecoxib compared with those who received placebo （P 〈 0.001）. Of these three changes, 84.6% of sites with dysplasia regressed in patients treated with celecoxib （P = 0.002） compared with 60% in the placebo group, suggesting that celecoxib was effective on the regression of dysplasia. COX-2 protein expression （P 〈 0.001） and COX-2 activity （P 〈 0.001） in the gastric tissues were consistently lower in celecoxib-treated patients compared with the placebo-treated subjects. Moreover, it was also shown that celecoxib suppressed cell proliferation （P 〈 0.01）, induced cell apoptosis （P 〈 0.01） and inhibited angiogenesis with decreased MVD （P 〈 0.001）. However, all of these effects were not seen in placebo-treated subjects. Furthermore, COX-2 inhibition resulted in the up-regulation of PPARy expression, a protective molecule with anti-neoplastic effects. CONCLUSION： H pylori eradication therapy followed by celecoxib treatment improves gastric precancerous lesions by inhibiting COX-2 activity, inducing apoptosis, and suppressing cell proliferation and angiogenesis.     

Cyclooxygenase (COX)-2 expression in a rat duodenoesophageal reflux model and chemoprevention of adenocarcinoma by the selective COX-2 inhibitor nimesulide]

The aim of this study is to investigate the cyclooxygenase (COX)-2 expression in esophageal epithelium of rat duodenoesophageal reflux model and the effect of a selective COX-2 inhibitor on esophageal adenocarcinogenesis in rats. A series of rats underwent a duodenoesophageal reflux procedure and were divided into 2 groups. One group was given commercial chow (control group), and the other group was given experimental chow containing nimesulide, a selective COX-2 inhibitor (nimesulide group). The animals were sacrificed sequentially after surgery and esophageal examinations were performed. In the control group, esophagitis, Barrett's esophagus (BE) and adenocarcinoma (EAC) were observed, and the frequency of these conditions increased with time. COX-2 expression, PGE(2) level and proliferative activity were up-regulated, predominantly in the inflamed esophageal epithelia, from the 10(th) week. In the nimesulide group, the esophagitis was mild and the frequency of BE was significantly lower than the control group, while EAC was not observed throughout the experiment. PGE(2) level and proliferative activity were lower in the nimesulide group than in the control group. COX-2 may play an important role in esophageal carcinogenesis through the activation of the inflammation-metaplasia-adenocarcinoma sequence. Nimesulide is effective in preventing BE and EAC by suppressing COX-2 activity.     

Rofecoxib inhibits cyclooxygenase 2 expression and activity and reduces cell proliferation in Barrett's esophagus

BACKGROUND & AIMS: Cyclooxygenase 2 (COX-2) is overexpressed in Barrett's esophagus and adenocarcinoma and up-regulated by acid or bile salt exposure. COX-2 inhibition with the selective inhibitor rofecoxib may be important in chemoprevention of esophageal adenocarcinoma by decreasing cell proliferation. METHODS: Biopsy specimens of esophagus, Barrett's esophagus, and duodenum were obtained at baseline from 12 patients and were compared with biopsy specimens obtained after 10 days of therapy with rofecoxib 25 mg orally daily. All patients were maintained asymptomatic on their proton pump inhibitor therapy throughout the study. COX-2 expression, proliferating cell nuclear antigen (PCNA) expression (proliferation marker), and prostaglandin E2 (PGE2) biopsy content (marker of COX activity) were assessed by immunoblotting and enzyme immunoabsorbence assays. RESULTS: At baseline, COX-2 expression was 3-fold higher in Barrett's esophagus than esophagus and duodenum (P < 0.05). After rofecoxib therapy, COX-2 expression in Barrett's esophagus decreased by 77% (P < 0.005). Similarly at baseline, PGE2 content was 2-fold higher in Barrett's esophagus than esophagus or duodenum. After rofecoxib therapy, PGE2 content decreased in Barrett's esophagus by 59% (P < 0.005). At baseline, PCNA expression was also 2-fold higher in Barrett's esophagus than squamous esophagus and duodenum (P < 0.005). After rofecoxib therapy, PCNA expression in Barrett's esophagus decreased by 62.5% (P < 0.005). CONCLUSIONS: Rofecoxib 25 mg orally once daily reduces COX-2 expression, PGE2 release, and cell proliferation in Barrett's esophagus. Together with acid suppressive therapy, rofecoxib may be a promising chemoprevention agent against dysplasia and esophageal adenocarcinoma.     

乙型肝炎病毒X蛋白和环氧合酶-2与乙型肝炎相关肝癌微血管生成和转移的关系及其可能机制

目的 探讨乙型肝炎病毒X蛋白(HBX)、环氧合酶-2(COX-2)在乙型肝炎相关性肝细胞肝癌(HCC)组织微血管生成和转移中的关系及其可能的调节机制. 方法选择84例乙型肝炎相关性肝细胞肝癌组织和22例非乙型肝炎相关性肝细胞肝癌组织,免疫组织化学法检测HBX、COX-2及血管内皮细胞表面抗原(CD34)的表达,光镜下记录微血管计数(MVD).Spearman相关性分析HBX、COX-2与乙型肝炎相关性HCC组织微血管生成及转移中的关系; Western blot和RT-PCR检测稳定转染HBX肝癌细胞HepG2(HepG2-X)中COX-2的变化;酶联免疫吸附法检测HepG2-X培养上清液中前列腺素E2(PGE2)表达水平及不同浓度(10、30、50 μ mol/L和70 μmol/L)COX-2选择性抑制剂塞来昔布作用后PGE2的表达水平;锥虫蓝拒染法检测细胞生长速度.结果 乙型肝炎相关性HCC组织中HBx、COX-2均高表达,HBx阳性表达组中COX-2阳性率为88.87%(55/62),明显高于HBx阴性组的31.82%(7/22,x2=27.188,P＜0.01)和非乙型肝炎相关性HCC组40.91%(9/22,x2=20.453,P＜0.01);HBx阴性表达的乙型肝炎相关性HCC组和非乙型肝炎相关性HCC组中COX-2阳性表达率差异无统计学意义(x2=0.393,P=0.531); HBx和COX-2在转移组表达高于无转移组(P＜0.01);HBx及COX-2的阳性表达组平均MVD值均明显高于HBx阴性组和非乙型肝炎相关性HCC组(P＜0.05),且转移组MVD高于无转移组(P＜0.01);门静脉侵犯组高于非侵犯组(P＜0.01);Spearman相关性分析结果提示HBx、COX-2在乙型肝炎相关性HCC组织微血管生成及转移中的表达呈正相关(Rs=0.568,P＜0.01);在HepG2-X细胞中,COX-2蛋白及mRNA表达水平与转染空载体的对照肝癌细胞HepG2 (空载体转染HepG2细胞,HepG2-PC)相比,均显著提高,并且细胞培养上清液中PGE2表达水平也显著提高;和转染空载体的对照细胞相比,塞来昔布对转染HBx基因的细胞分泌PGE2具有更强的抑制作用.结论 HBx、COX-2在乙型肝炎相关性HCC中有较高的表达水平,二者呈正相关,与HCC微血管生成和侵袭转移密切相关.COX-2可能是HBx促使肝癌组织微血管生成和转移的一个重要中间分子,其可能的调节机制是通过HBx、COX-2及PGE2作为信号转导通路在HCC的浸润与迁移,在微血管生成与转移的过程中发挥双重作用.     

Cyclooxygenase-2 and prostaglandins in articular tissues

OBJECTIVES: To provide an overview on: 1) the expression of cyclooxygenase (COX)-2 in articular tissues; 2) the role of prostaglandin E2 (PGE2) in these tissue functions; and 3) clinical trials with COX-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs) (coxibs). METHODS: MEDLINE search was performed using the key words "cyclooxygenase," "prostaglandin," "osteoarthritis" (OA), and "rheumatoid arthritis" (RA). Selected publications related to clinical trials with coxibs also are included. RESULTS: COX-2 is upregulated in inflamed joint tissues and is responsible for elevated PGE2 production. The overexpression of COX-2 is likely induced by proinflammatory mediators such as interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF) alpha. However, the exact molecular mechanisms through which the expression of COX-2 is regulated remain to be elucidated. Several studies suggest that PGE2 is involved in inflammation, apoptosis, angiogenesis, and possibly structural changes that characterize arthritic diseases. NSAIDs are prescribed for the treatment of OA and RA and provide effective relief from symptoms; however, serious gastrointestinal complications occur with their use. The clinical efficacy of NSAIDs is primarily related to the inhibition of COX-2, whereas much of the toxicity is related to COX-1 inhibition. Selective COX-2 inhibitors (coxibs) that spare COX-1 at therapeutic doses are more effective than placebo and as effective as other NSAIDs for relief of symptoms of OA and RA, and have significantly improved gastrointestinal safety and tolerability. However, some studies showed that COX-2-selective inhibitors still have classic NSAID complications. CONCLUSIONS: Overexpression of COX-2 protein in articular tissues is a characteristic feature of arthritic diseases. However, the molecular mechanisms involved in the regulation of COX-2 expression and activity are still unclear. Elucidating the mechanisms of COX-2 expression and PGE2 production and action will help identify novel and more selective potential drug targets in the treatment of arthritic diseases.     

Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus

BACKGROUND & AIMS: Carcinogenesis in Barrett's esophagus (BE) is associated with an increased expression of cyclooxygenase (COX) 2. However, there has been no direct evidence that inhibition of COX-2 prevents cancer in BE. We studied the effect of MF-Tricyclic, a selective COX-2 inhibitor, on the development of BE and adenocarcinoma in a rat model. METHODS: Four weeks after esophagojejunostomy, 105 Sprague-Dawley rats were randomized to a chow containing MF-Tricyclic or Sulindac, or a placebo. Ninety-six (92%) rats completed the study and were sacrificed at 28 +/- 2 weeks. The animals were assessed for the presence of cancer, tumor volume, BE, degree of inflammation, and COX-2 expression and activity. RESULTS: MF-Tricyclic and Sulindac reduced the relative risk of development of esophageal cancer by 55% (95% confidence interval [CI] = 43%-66%, P < 0.008) and by 79% (95% CI = 68%-87%, P < 0.001), respectively, compared with controls. No significant differences were noted in the risk of esophageal cancer between the MF-Tricyclic and the Sulindac group (P = 0.34). The median tumor volume was not significantly different among the 3 groups (P = 0.081). Moderate to severe degree of inflammation was significantly more common (P = 0.005) in the control compared with the MF-Tricyclic and the Sulindac group; however, the prevalence of BE was not significantly different between groups (P = 0.98). Rats in the control group had higher tissue PGE2 level compared with the MF-Tricyclic and Sulindac groups (P = 0.038). CONCLUSIONS: Selective and nonselective COX-2 inhibitors can inhibit inflammation, COX-2 activity, and development of adenocarcinoma induced by reflux. This provides direct evidence that COX-2 inhibitors may have chemopreventive potential in BE.