环氧合酶-2抑制剂对大鼠急性肺损伤的作用

目的探讨急性肺损伤（ALI）肺组织环氧合酶－2（COX-2）mRNA表达的变化以及选择性COX－2抑制剂Meloxicam的干预作用。方法脂多糖（LPS）诱发大鼠ALI模型,采用逆转录-聚合酶链反应,检测其肺组织COX-2mRNA表达并观察其前列腺素（PGs）、动脉血氧分压（PaO2）及病理变化。结果静息状态的大鼠肺组织表达少量的COX-2mRNA,在ALI大鼠肺组织COX-2mRNA大量表达,Meloxicam可减轻肺组织病理损伤、降低PGs产量,使PaO2下降程度减轻。结论COX-2是ALI时PGs升高的主要同工酶,Meloxicam可抑制COX-2活性,对ALI具有一定的防治作用。     

环氧合酶-2抑制剂对大鼠胃肿瘤的预防作用

目的探讨环氧合酶-2（COX-2）抑制剂塞莱昔布对实验大鼠胃肿瘤发生的预防作用。方法雌性SD大鼠100只,除正常对照组20只外,其余80只大鼠给予苯并芘混悬液（5 mg/ml）50 mg/kg灌胃,每周2次,共4周。给药后4周,将大鼠随机分成模型对照组20只、塞莱昔布15、10和5 mg/kg组各20只;正常对照组及模型对照组喂养普通饲料,塞莱昔布大、中、小剂量组喂养相应的含药饲料。结果塞莱昔布中、大剂量组与模型对照组比较,肿瘤发生数量及肿瘤发生率均呈现明显抑制作用（P〈0.05或〈0.01）,肿瘤细胞分化程度较高;小剂量组肿瘤组织大部分细胞分化较低。结论 COX-2抑制剂有预防实验动物胃肿瘤的作用。     

环氧合酶-2抑制剂尼美舒利对大鼠肝纤维化的影响

环氧合酶-2(COX-2)是一种诱导酶，在大部分正常组织中无表达，可在炎性介质等的作用下诱导表达。Nanji等在肝纤维化的研究中发现，COX-2的表达与肝内炎症有关。本实验应用选择性COX-2抑制剂尼美舒利(NS)观察其对大鼠肝纤维化的影响。γ-干扰素(IFN)具有抗肝纤维化的作用已成共识，故以其作疗效对照。     

环氧合酶—2对溃疡性结肠炎致病作用的研究进展

环氧合酶-2（COX-2）是一种与炎症反应密切相关的诱导型环氧合酶，可在多种刺激因子作用下激活表达，促进炎症反应的发生，本综述COX-2及其代谢产物对溃疡性结膜炎的致病作用及在诱导结肠炎相关性结直肠癌中作用的研究进展。     

选择性环氧合酶-2抑制剂与COX-2/5-脂氧合酶双酶抑制剂对食管鳞状细胞癌细胞增殖的影响

目的比较选择性环氧合酶-2（COX-2）抑制剂与COX-2/5-脂氧合酶（5-LOX）双酶抑制剂对食管鳞状细胞癌（ESCC）细胞增殖的影响,探讨单一抑制COX-2对抑制ESCC细胞增殖可能存在的局限性。方法 COX-2/5-LOX双抑制剂licofelone和选择性COX-2抑制剂NS-398分别作用于ESCC细胞株TE-1,设药物处理组、溶媒（DMSO）对照及空白对照组。两种药物分别以25μmol/L、50μmol/L、75μmol/L和100μmol/L浓度作用24 h及48 h。四唑单钠盐（CCK-8）法检测细胞增殖;RT-PCR和W esternb lot检测mRNA及蛋白表达;ELISA法检测PGE2和LTB4含量;流式细胞术检测细胞周期。结果 TE-1细胞的浓度及时间依赖性增殖抑制只出现于licofelone处理组。licofelone及NS-398对COX-2 mRNA、蛋白及下游产物PGE2表达均有时间、浓度依赖性抑制作用（P〈0.05）,但仅licofelone处理组出现5-LOX mRNA、蛋白及下游产物LTB4的时间、浓度依赖性表达抑制。100μmol/L licofe-lone及50μmol/L NS-398作用24 h后TE-1细胞分别有67.1%、63.8%处于G0/G1期,显著高于对照组（P〈0.05）。结论单一抑制COX-2并不能稳定抑制TE-1细胞的增殖。较高浓度NS-398可增加5-LOX分流,减弱COX-2抑制对细胞增殖的负性影响。     

环氧合酶—2与肺癌

本文就环氧合酶-2(COX-2)在肿瘤发生、发展、预后中的研究现状以及COX-2和COX-2抑制剂在肺癌中的作用作一综述。COX-2抑制剂可能成为治疗肺癌的新途径。     

环氧合酶-2在小儿慢性炎症胃黏膜中的表达

目的探讨小儿时期不同炎症胃黏膜环氧合酶也（COX-2）表达特点及可能意义。方法随机抽取正常胃黏膜、普通慢性胃炎、幽门螺杆菌（Hp）相关慢性胃炎、慢性胃炎伴肠上皮化生（无却感染）共110例蜡块重新切片作常规病理学评估，并应用免疫组化法分析胃黏膜COX-2表达。结果COX-2在正常胃黏膜无表达；普通胃炎组9例轻度表达（22．5％）；坳胃炎组27例轻度表达（67．5％），中度表达2例（5．0％）；肠化组轻度表达6例（30．0％）。坳相关胃炎较普通胃炎组及肠化组（均为轻度炎症）COX-2阳性率细显著升高（P=0．000和P=0．002）；普通胃炎组中重度炎症COX-2阳性率较轻度炎症高（P=0．025）。慢性胃炎伴肠化组和普通胃炎组炎症程度无差别（P：0．527），其COX-2阳性表达率一致（P=0．542）。结论小儿胃炎COX-2表达较弱，却感染可诱发COX-2表达，其表达率随炎症程度加重而升高，COX-2表达和肠化无关。小儿早期轻度表达COX-2，其生理意义可能与成人有所不同。     

环氧合酶-2与动脉粥样硬化

动脉粥样硬化(Atherosclerosis,AS)是一种由众多炎性细胞因子参与并伴有细胞增生的血管慢性炎症反应过程.环氧合酶-2( COX-2)是COX家族的重要成员,在许多疾病中表达上调.AS病变处COX-2表达增多的现象提示COX-2在AS发生发展中具有重要作用,可能是一个抗动脉粥样硬化的新靶点.COX-2抑制剂被用来治疗AS,其安全性尚存在争议.     

环氧合酶-2和胰腺癌

胰腺癌目前发病率有上升的趋势,其死亡率非常高.环氧合酶-2（COX-2）在诸多肿瘤尤其是消化道肿瘤中起着重要作用,有研究发现COX-2在胰腺癌的发生、转移、治疗和化学预防中起着重要作用.本文就此作一综述.     

刺五加胶囊对抑郁大鼠结肠氧自由基及环氧合酶-2的影响

[目的]观察刺五加胶囊对抑郁症大鼠结肠氧自由基(OFR)和环氧合酶-2(COX-2)的影响及结肠的保护作用.[方法]建立大鼠抑郁模型.予以刺加五胶囊(300、600、900 mg/kg)与5-氨基水杨酸(5-ASA)灌肠给药2周后,采用生化方法检测大鼠结肠组织中超氧化物歧化酶(SOD)、丙二醛(MDA),免疫组化方法检测结肠组织COX-2的表达.[结果]抑郁模型大鼠结肠组织中MDA升高(P＜0.01),SOD降低(P＜0.01),COX-2表达升高(P＜0.01);不同剂量的刺五加胶囊均可使抑郁模型大鼠结肠组织MDA降低(P＜0.05),SOD升高(P＜0.05),并能下调COX-2的表达(P＜0.01).[结论]刺五加胶囊可能通过改变抑郁模型大鼠结肠组织MDA,SOD和COX-2的表达来改善其结肠的功能.     

Cyclooxygenase-2 inhibitors, nonsteroidal anti-inflammatory drugs, and cardiovascular risk

Cyclooxygenase-2 (cox-2) inhibitors, also known as coxibs, were introduced with the promise that they would provide pain relief similar to that of traditional nonsteroidal anti-inflammatory drugs (NSAIDs) but would be better tolerated with lower risk of gastrointestinal (GI) side effects. Although coxibs were associated with lower GI risk, experimental and observational data raised the specter of increased cardiovascular risk associated with this class of drugs. This article describes the pharmacologic and biologic basis of cardiovascular risk associated with coxibs, summarizes the evidence for cardiovascular risk associated with cox-2 inhibitors, and weighs the risks and potential benefits of pain management with these agents.     

环氧化酶-2与糖尿病

糖尿病通常伴有慢性低水平的炎性反应.目前研究证实环氧化酶2(COX-2)在糖尿病及其并发症的发病中起重要作用.启动子的激活、高糖刺激、炎性因子、自由基、十二脂氧化酶、前列腺素E等多种因素的作用下,COX-2表达显著上调.随着对COX-2的进一步研究,为糖尿病的预防、诊断以及治疗提供了新的思路.     

Cyclooxygenase-2 expression in primary human colorectal cancers and bone marrow micrometastases

BACKGROUND: Both the expressions of the inducible form of cyclooxygenase-2 and the presence of bone marrow micrometastases are poor prognostic markers in patients with colorectal carcinoma. AIMS: As cyclooxygenase-2 expression in these tumours is associated with increased metastatic potential in vitro, our objectives were to determine the relationship between cyclooxygenase-2 and haematogenous spread to bone marrow. PATIENTS AND METHODS: Thirty-two patients with resection of colorectal carcinoma were evaluated (median age: 69.5 years). Bone marrow was obtained from all patients from both iliac crests before manipulation of the primary tumour. The tumours were of varying stages at diagnosis (5 Dukes' A, 14 Dukes' B, 11 Dukes' C and 2 Dukes' D). Tumour sections were stained for cyclooxygenase-2 using the avidin-biotin immunohistochemical technique. Extent of staining was graded depending on the percentage of epithelial cells staining positive for cyclooxygenase-2. Micrometastases were detected by staining contaminant cytokeratin-18 positive cells in the bone marrow aspirates by either immunohistochemical (ARAAP) or immunological (flow cytometry) methods. Fisher's exact probability test was used to calculate statistical significance. RESULTS: Cyclooxygenase-2 expression in the primary tumour was detected in 72% of the patients. Twelve (38%) patients had bone marrow micrometastases detected by either immunohistochemistry or flow cytometry. Of the 12 patients who had bone marrow micrometastases, 8 tumours demonstrated increased expression of cyclooxygenase-2 protein (66.6%). In contrast, 9 out of the 20 (45%) patients in whom micrometastases were not detected expressed increased levels of cyclooxygenase-2 (P = 0.29). When dividing the patients into subgroups of localised (Dukes' A and B) versus disseminated (Dukes' C and D) disease, there was no further association between cyclooxygenase-2 expression and bone marrow micrometastases (P = 0.179 and 1.0). CONCLUSION: In this pilot study, there was no association between cyclooxygenase-2 expression and bone marrow micrometastases in patients with otherwise localised or disseminated disease.     

Cyclooxygenase-2 Expression in Colorectal Adenomas

PURPOSE: Cyclooxygenase-2 is an important target for nonsteroidal anti-inflammatory drugs in suppressing colorectal tumorigenesis. To evaluate the role of cyclooxygenase-2 in sporadic colorectal adenoma, we correlated cyclooxygenase-2 expression in adenomas with other adenoma characteristics. METHODS: Cyclooxygenase-2 expression was evaluated immunohistochemically in 95 endoscopically resected colorectal adenomas. RESULTS: Cyclooxygenase-2 was expressed mainly in the cytoplasm of adenoma cells, where it was seen in 74 percent (70/95) of adenomas. Expression was related significantly to grade of dysplasia (P < 0.001) and tumor size (P = 0.028). Multivariate logistic regression analysis showed cyclooxygenase-2 expression in adenoma cells to be independently associated with grade of dysplasia (P = 0.001). CONCLUSION: Observed associations suggest that cyclooxygenase-2 plays an important role in progression of the adenoma-to-carcinoma sequence.     

前列腺素E2在环氧合酶-2促胰腺癌新生血管生成中的介导作用

目的 探讨环氧合酶-2(COX-2)促进胰腺癌新生血管生成过程中前列腺素E2(PGE2)的介导作用，进一步揭示COX-2促进胰腺癌生长的机制。方法 体外培养胰腺癌细胞株PC-3，分别应用酶联免疫吸附(ELISA)和放射免疫(RIA)等方法，检测选择性COX-2抑制剂Celebrex对胰腺癌PC3细胞血管内皮生长因子(VEGF)和PGR表达的调节作用，并观察外源性PGE2对Celebrex调节VEGF表达的干预。建立裸鼠PC3细胞移植瘤，Western印迹检测Celebrex对胰腺癌组织VEGF表达的影响，RIA测定Celebrex对胰腺癌组织PGB变化的调节。结果 随着Celebrex作用浓度的提高以及作用时间的延长，PC3细胞分泌的VEGF和PGE2受到抑制，呈时间和剂量依赖性。外源性PGE2显著上调Celebrex作用后PC-3细胞VEGF蛋白表达，呈剂量依赖性，体内实验表明，Celebrex可显著抑制移植瘤组织VEGF和PGE2的表达。结论 COX-2参与了PC-3细胞VEGF分泌的调节，进而促进胰腺癌新生血管形成，而PGE2则在该过程中起着重要的介导作用。     

Cyclooxygenase-2 Expression as a New Marker for Patients with Colorectal Cancer

PURPOSE: Epidemiologic studies indicate that the use of nonsteroidal anti-inflammatory drugs, which inhibit cyclooxygenase activity, reduce the risk of colorectal cancer. In addition, several studies demonstrate increased expression of cyclooxygenase-2 in human colorectal cancer tissues. However, the role of cyclooxygenase-2 expression in colorectal cancer has not yet been fully established. The aim of this study was to clarify the clinicopathologic significance of cyclooxygenase-2 expression in human colorectal cancer. METHODS: A total of 232 surgically resected colorectal cancer specimens were analyzed immunohistochemically with the use of a murine anti-human cyclooxygenase-2 monoclonal antibody. Cyclooxygenase-2 expression was then compared with clinicopathologic background and survival outcome. RESULTS: Cyclooxygenase-2 was expressed in the cytoplasm of the cancer cells but not in normal epithelium. Cyclooxygenase-2 expression was noted in 71.6 percent (166/232) of the cancer patients and correlated significantly with histologic type (P = 0.033), depth of invasion (P = 0.016), pathologic stage (P = 0.020), and metachronous liver metastasis (P = 0.001). Multivariate analysis for factors associated with metachronous liver metastasis showed that cyclooxygenase-2 expression was one of the independent risk factors, second only to lymph node metastasis. Patients with cyclooxygenase-2 expression showed a significantly poorer outcome compared with those without cyclooxygenase-2 expression (P = 0.002). CONCLUSION: Cyclooxygenase-2 expression in the primary lesion may be a useful marker for evaluating prognosis and liver metastasis in patients with colorectal cancer.     

Cyclooxygenase-2 expression on ifosfamide-induced hemorrhagic cystitis in rats

Purpose Hemorrhagic cystitis (HC) is a limiting side effect of chemotherapy with ifosfamide (IFS). In this study, we investigated the participation of cyclooxygenase-2 (COX-2) upon ifosfamide-induced HC. Methods Male Wistar rats (150–200 g; six rats per group) were treated with saline, IFS (400 mg/kg, i.p.) and analyzed by changes in bladder wet weight, macroscopic and microscopic parameters, and COX-2 expression. In other groups etoricoxib (selective COX-2 inhibitor), indomethacin (non-selective COX inhibitor), thalidomide (selective TNF-α inhibitor), pentoxifyllin (non-selective TNF-α inhibitor) were added 1 h before IFS administration. The classical protocol using three doses of Mesna was also evaluated and compared with two extra doses of etoricoxib or indomethacin. Results COX-2 was expressed significantly 24 h after IFS administration mainly in myofibroblasts and mast cells evaluated by immunohistochemistry. Treatment 1 h before IFS injection with etoricoxib, indomethacin, thalidomide, and pentoxifylline reduced COX-2 expression and some macroscopic and microscopic parameters in IFS-induced HC. Moreover, addition of etoricoxib or indomethacin with the last two doses of Mesna was more efficient than three doses of Mesna alone when evaluated microscopically. Conclusions COX-2 participates in the pathogenesis of IFS-induced HC and the treatment with COX and TNF-α inhibitors reduced COX-2 expression. The addition of COX-inhibitors to the last two doses of Mesna represents a new therapeutic strategy of preventing HC.     

选择性环氧化酶-2抑制剂对载脂蛋白E基因敲除小鼠动脉粥样硬化影响的实验研究

目的:观察选择性环氧化酶-2抑制剂对载脂蛋白E基因敲除小鼠动脉粥样硬化进展的影响。方法:8周龄载脂蛋白E基因敲除小鼠分为塞来昔布(celecoxib)组及安慰剂组,均予高脂饮食喂养,分别以特异性环氧化酶-2抑制剂塞来昔布及安慰剂灌胃8周;同龄野生型小鼠为正常对照组。酶法分析测定血脂,油红O染色观察主动脉根部粥样硬化斑块大小。结果:塞来昔布组与安慰剂组之间实验前后血脂水平均无差异,但均高于正常对照组(胆固醇水平P<0.01,甘油三酯水平P<0.05)。油红O染色显示,塞来昔布组及安慰剂组可见明显粥样硬化斑块形成;前者的斑块面积及斑块面积/原管腔面积均较后者显著降低(P均<0.01)。结论:用选择性环氧化酶-2抑制剂塞来昔布进行抗炎干预可抑制动脉粥样硬化的进展,其机制与调脂无关。针对炎症机制有望有效控制动脉粥样硬化的发生发展。     

环氧合酶-2在反流性食管炎大鼠食管组织中表达的实验研究

背景：环氧合酶（COX）-2在炎症、肿瘤等的发生、发展过程中发挥重要作用，但其在反流性食管炎（RE）中的作用尚未明确。目的：研究COX-2在混合性RE大鼠食管组织中的表达，探讨COX-2的表达与RE的关系。方法：采用贲门肌切开术加十二指肠半结扎术建立混合性RE大鼠模型。22只健康Sprague-Dawley大鼠随机分为RE模型组（n=12）和假手术组（n=10），于术前和术后1周测定食管下段和胃液pH值。处死大鼠，分别应用放射免疫测定和免疫组化方法检测食管组织中前列腺素（PG）E2的含量和COX-2的表达，光镜观察食管组织的形态学改变。结果：RE模型组术后食管下段pH值显著低于假手术组（P〈0．05），胃液pH值则显著高于假手术组（P〈0．05）；食管组织PGE2含量亦较假手术组显著增高（P〈0．001），COX-2表达均为阳性，假手术组食管组织中无COX-2表达。光镜观察显示RE模型组食管黏膜病理损害明显。结论：COX-2高表达和PGE2含量增高参与了混合性RE的发生、发展过程，COX-2可能通过升高PGE2含量而在RE的发病中起重要作用。     

3种选择性环氧合酶-2抑制剂对肝细胞癌生长的影响

背景肝细胞癌(HCC)中有环氧合酶(COX)-2表达,非甾体抗炎药阿司匹林可能通过抑制COX-2的表达而抑制HCC生长.目的比较3种选择性COX-2抑制剂美洛昔康、赛来昔布和罗非昔布对人肝癌细胞株SMMC-7721 生长的影响,观察高选择性COX-2抑制剂罗非昔布对裸鼠HCC原位移植瘤生长的影响.方法采用3H-胸腺嘧啶核苷(3H-TdR)掺入检测SMMC-7721细胞的DNA合成情况;采用免疫细胞化学染色检测增殖细胞核抗原(PCNA)的表达;采用DNA原位末端标记(TUNEL)染色检测细胞凋亡.给予HCC原位移植瘤裸鼠罗非昔布每日30 mg/kg 8周,测量肿瘤体积和重量.结果美洛昔康、赛来昔布和罗非昔布均能显著抑制SMMC-7721细胞的3H-TdR掺入,其抑制作用呈剂量依赖性,50%抑制浓度(IC50)分别为8.55×10-8mol/L、1.22×10-8mol/L和6.27×10-9 mol/L.3种选择性OX-2抑制剂(1×10-5 mol/L)作用24 h均可明显降低SMMC-772I细胞的PCNA表达,使细胞凋亡指数较对照组显著增高(14.6%±2.8%、21.6%±3.6%和27.1%±3.5%对1.0%±0.7%,P＜0.01),COX-2抑制剂的选择性越高,凋亡指数也越高(P＜0.01).罗非昔布组裸鼠的HCC原位移植瘤显著小于对照组,体积抑瘤率和重量抑瘤率分别为73.2%和78.1%.结论3种选择性COX-2抑制剂均能在体外有效抑制SMMC-7721细胞的生长,选择性越高,抑制作用越强.罗非昔布在体内能抑制HCC的生长,可能成为治疗HCC的有效药物.