Pathogenesis of chronic enteropathy associated with the SLCO2A1 gene:Hypotheses and conundrums

Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.

咬合重建固定义齿修复术对牙周病伴牙列缺损患者颞下颌功能、脑血流速度及龈沟液IL-23、PGE_(2)的影响

目的 探讨咬合重建固定义齿修复术对牙周病(PD)伴牙列缺损患者颞下颌功能、脑血流速度及龈沟液白介素23(IL-23)、前列腺素E_(2)(PGE_(2))的影响。方法 选取2016年7月至2019年8月郑州大学第五附属医院收治的130例PD伴牙列缺损患者,根据治疗方案分为对照组和试验组,各65例。对照组接受垫式可摘局部义齿修复,试验组接受咬合重建固定义齿修复。治疗后观察6个月,统计两组修复效果、咀嚼功能、肌肉压痛指数、颞下颌关节紊乱指数、颞下颌关节功能障碍指数、龈沟液IL-23、PGE_(2)、舒张期末峰流速(Vd)、右侧大脑中动脉的收缩期峰流速(Vs)、平均峰流速值(Vm)、治疗满意度。结果 试验组总有效率高于对照组(P<0.05),咀嚼功能优良率高于对照组(P<0.05);修复6个月后试验组颞下颌关节功能障碍指数、肌肉压痛指数、颞下颌关节紊乱指数低于对照组,咀嚼状态下大脑中动脉Vs、Vd、Vm大于对照组(P<0.05),龈沟液IL-23水平低于对照组,PGE_(2)水平高于对照组(P<0.05),试验组语音功能、固位功能、咀嚼功能满意度高于对照组(P<0.05)。结论 咬合重建固定义齿修复术可改善PD伴牙列缺损患者咀嚼功能、颞下颌功能及脑血流速度,调节龈沟液IL-23、PGE_(2)水平,提高治疗满意度。

慢性牙周炎患者血清HMGB-1、TREM-1、Visfatin、PGE2水平与其他炎症因子的关系

目的探讨慢性牙周炎患者血清高迁移率族蛋白B-1(HMGB-1)、人髓系细胞触发受体-1(TREM-1)、内脂素(Visfatin)、前列腺素E2(PGE2)水平与其他炎症因子的关系。方法选择2018年3月至2020年3月攀枝花市中心医院诊治的90例慢性牙周炎患者作为牙周炎组,根据慢性牙周炎活动期诊断标准进一步分为静止期组(42例)以及活动期组(48例)。选择同期进行健康体检的90名健康者作为对照组。采用酶联免疫吸附法检测各组血清HMGB-1、TREM-1、Visfatin、PGE2以及肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)和白介素-2(IL-2)水平。采用Pearson法分析慢性牙周炎患者血清HMGB-1、TREM-1、Visfatin、PGE2与炎症因子相关性。结果与对照组相比,牙周炎组血清HMGB-1、TREM-1、Visfatin、PGE2、TNF-α、IL-6、IL-2水平明显升高(P<0.05)。与静止期患者相比,活动期患者血清HMGB-1、TREM-1、Visfatin、PGE2、TNF-α、IL-6、IL-2水平升高(P<0.05)。Pearson相关性分析显示,慢性牙周炎患者血清HMGB-1、TREM-1、Visfatin、PGE2与炎症因子TNF-α、IL-6、IL-2呈正相关性(P<0.05)。结论慢性牙周炎患者血清HMGB-1、TREM-1、Visfatin、PGE2水平显著升高,且与炎症因子密切相关,四者可能参与了慢性牙周炎的发生发展过程,在慢性牙周炎的病情评估和诊断中具有一定的参考价值。

胃食管反流病患者反流症状评分与血清PGE2、Ghrelin及GAS水平的相关性分析

目的探讨胃食管反流病(GERD)患者反流症状评分与血清前列腺素E_(2)(PGE_(2))、胃饥饿素(Ghrelin)及胃泌素(GAS)水平的相关性。方法选择2019年8月至2022年8月陕西航天医院收治的GERD患者150例(GERD组)和同期健康体检者120例(对照组)为研究对象,采用酶联免疫吸附试验检测血清PGE_(2)、Ghrelin和GAS水平。比较GERD组与对照组血清PGE_(2)、Ghrelin、GAS水平和胃食管反流病问卷(GERD-Q)评分,分析不同GERD-Q评分患者血清PGE_(2)、Ghrelin、GAS水平,采用Pearson相关分析GERD患者GERD-Q评分与血清PGE_(2)、Ghrelin、GAS水平的相关性。结果GERD组GERD-Q评分和血清PGE_(2)水平高于对照组,血清Ghrelin、GAS水平低于对照组,差异有统计学意义(P<0.05)。GERD-Q评分为7~10分者血清PGE_(2)水平低于GERD-Q评分为11~14分和15~18分者,血清Ghrelin、GAS水平高于GERD-Q评分为11~14分和15~18分者,差异有统计学意义(P<0.05);GERD-Q评分为11~14分者血清PGE_(2)水平低于GERD-Q评分为15~18分者,血清Ghrelin、GAS水平高于GERD-Q评分为15~18分者,差异有统计学意义(P<0.05)。Pearson相关分析显示,GERD患者GERD-Q评分与血清PGE_(2)水平呈正相关(r=0.510,P<0.05),与血清Ghrelin、GAS水平均呈负相关(r=-0.524、-0.568,P<0.05)。结论血清PGE_(2)、Ghrelin、GAS水平均与GERD患者GERD-Q评分相关,有望成为评估患者反流症状严重程度的血清学标志物。

多不饱和脂肪酸对Δ15 Des转基因小鼠前列腺素E_(2)水平的影响

目的探讨多不饱和脂肪酸(PUFAs)对Δ15脂肪酸去饱和酶(Δ15 Des)转基因小鼠前列腺素E_(2)(PGE_(2))水平的影响。方法取C57BL/6野生型(WT)雄性小鼠和Δ15 Des转基因雄性小鼠作为对照组(n=5,WT组)和实验组(n=5,TG组),6%花生四烯酸(ARA)饲养8周,每周记录小鼠体质量变化;8周后麻醉处死2组小鼠,冰上分离小鼠肝脏、睾丸及肌肉组织,采用气相色谱(GC)检测2组小鼠各组织中脂肪酸(FAs)的组成及水平,采用酶联免疫吸附(ELISA)和实时荧光定量PCR(RT-qPCR)测定2组小鼠各组织中PGE_(2)的水平及前列腺素E合酶1(PTGES1)、前列腺素E合酶2(PTGES2)信使RNA(mRNA)的相对表达。结果第1~8周,2组小鼠体质量均在增长,2组间比较、差异无统计学意义(P>0.05);WT组小鼠各组织中PUFAs主要是欧米伽-6 PUFAs(n-6 PUFAs);与WT组相比,TG组小鼠各组织中ARA水平降低、二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)水平升高(P<0.05或P<0.01),睾丸组织中亚油酸(LA)水平升高、二十二碳四烯酸(DTA)水平降低(P<0.05);TG组小鼠睾丸、肌肉组织中PGE_(2)水平低于WT组(P<0.05或P<0.01);TG组小鼠肝脏、睾丸组织中PTGES1、PTGES2 mRNA表达低于WT组(P<0.05或P<0.01)。结论PUFAs可减少Δ15 Des转基因小鼠ARA的合成,降低与PGE_(2)相关的合成酶表达,从而调节体内PGE_(2)的水平。

经皮微创脊柱内固定治疗对创伤性胸腰椎骨折患者外周血TNF-α、MCP及PGE2水平的影响

目的 探究经皮微创脊柱内固定治疗对创伤性胸腰椎骨折患者外周血肿瘤坏死因子-α(TNF-α)、单核细胞趋化蛋白(MCP)及前列腺素E2(PGE2)水平的影响。方法 选取2018年7月—2021年8月收治创伤性胸腰椎骨折152例为研究对象。根据治疗方案不同分为对照组74例(给予Wiltse入路手术治疗)和观察组78例(给予经皮微创脊柱内固定治疗)。比较2组手术相关指标,手术前后TNF-α、MCP、PGE2水平和Oswestry功能障碍指数(ODI)评分变化,以及术后并发症发生情况。结果 观察组手术总时间长于对照组,术中出血量少于对照组,术后住院时间及骨折愈合时间短于对照组(P<0.01)。术后1、3、7 d, 2组TNF-α、MCP及PGE2水平均较术前明显升高,但观察组低于对照组(P<0.05)。术后1周、3个月、6个月,2组ODI评分均较术前明显降低,且观察组低于对照组(P<0.05)。观察组术后并发症总发生率为2.56%(2/78)低于对照组10.81%(8/74)(P<0.05)。结论 经皮微创脊柱内固定治疗可明显降低创伤性胸腰椎骨折患者外周血TNF-α、MCP及PGE2水平,促进患者恢复。

Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E_2 and cytokines

AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtime polymerase chain reaction, The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells （PBMC） was studied by measuring PGE2, cytokines and chemokines in the supernatant. The effect of SCFAs in vivo was examined by intraplantar injection into rat paws. RESULTS： Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE2 and that this effect can be enhanced in the presence of lipopolysaccharide （LPS）. In addition, we demonstrate that PGE2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1 （MCP-1） production and LPS-induced interleukin-10 （IL-10） production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE2, MCP-1 and IL-10 after 5CFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-7 in human PBIVlC. Finally, we show that SCFAs and LPS can induce PGE2 production in vivo by intraplantar injection into rat paws （P 〈 0.01）. CONCLUSION： SCFAs can have distinct antiinflammatory activities due to their regulation of PGE2, cytokine and chemokine release from human immune cells.

Thymoquinone suppresses migration of Lo Vo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activation

AIM To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration. METHODS Our experiments used high dose thymoquinone (TQ) as an inhibitor to arrest LoVo (a human colon adenocarcinoma cell line) cancer cell growth, which was detected by cell proliferation assay and immunoblotting assay. Low dose TQ did not significantly reduce LoVo cancer cell growth. Cyclooxygenase 2 (COX-2) is an enzyme that is involved in the conversion of arachidonic acid into prostaglandin E2 (PGE2) in humans. PGE2 can promote COX-2 protein expression and tumor cell proliferation and was used as a control. RESULTS Our results showed that 20 mu mol/L TQ significantly reduced human LoVo colon cancer cell proliferation. TQ treatment reduced the levels of p-PI3K, p-Akt, p-GSK3 beta, and beta-catenin and thereby inhibited the downstream COX-2 expression. Results also showed that the reduction in COX-2 expression resulted in a reduction in PGE2 levels and the suppression of EP2 and EP4 activation. Further analysis showed that TG treatment inhibited the nuclear translocation of beta-catenin in LoVo cancer cells. The levels of the cofactors LEF-1 and TCF-4 were also decreased in the nucleus following TQ treatment in a dose-dependent manner. Treatment with low dose TQ inhibited the COX-2 expression at the transcriptional level and the regulation of COX-2 expression efficiently reduced LoVo cell migration. The results were further verified in vivo by confirming the effects of TQ and/or PGE2 using tumor xenografts in nude mice. CONCLUSION TQ inhibits LoVo cancer cell growth and migration, and this result highlights the therapeutic advantage of using TQ in combination therapy against colorectal cancer.

Elevated serum prostaglandin E2 predicts the risk of infection in hepatitis B virus-related acute-on-chronic liver failure patients

Objective: To evaluate the serum Prostaglandin E2(PGE2) level in Acute-on-chronic liver failure(ACLF) and determine its predicative value for infection.Methods: From April 2014 to April 2015, ninety-one patients with hepatitis B virus and ACLF but without infection were enrolled into this prospective study that was carried out at our Hospital. Twenty patients with stable chronic hepatitis B were enrolled from the outpatient department and twenty healthy control subjects without any disease were enrolled from hospital staff. Serum PGE2 levels were determined using ELISA at enrollment. Clinical and laboratory parameters were collected. Receiver operating characteristic(ROC) curves were used to determine optimal cut-off values to predict infection.Results: Significantly higher PGE2 levels were found in patients with ACLF in comparison with healthy controls and patients with stable CHB(P < 0.000 1). In ACLF patients, PGE2 levels were significantly higher in patients that eventually developed infection than those without this complication(P < 0.000 1). ROC analysis showed that serum PGE2(area under the ROC curve, 0.83) could predict infection in patients with ACLF with sensitivity of 78.4% and specificity of 81.5% using a threshold of 141 pg/m L.Conclusions: Serum PGE2 is associated with the susceptibility to secondary infections for patients with ACLF. Increased PGE2 serum levels may serve as a potential biomarker for developing infections in ACLF patients.

Cyclooxygenase-2 expression is associated with initiation of hepatocellular carcinoma, while prostaglandin receptor-1 expression predicts survival

AIM to determine whether cyclooxygenase-2(COX-2) and prostaglandin E1 receptor(EP1) contribute to disease and whether they help predict prognosis.METHODS We retrospectively reviewed the records of 116 patients with hepatocellular carcinoma(HCC) who underwent surgery between 2008 and 2011 at our hospital. Expression of COX-2 and EP1 receptor was examined by immunohistochemistry of formalin-fixed, paraffinembedded tissues using polyclonal antibodies. Possible associations between immunohistochemical scores and survival were determined.RESULTS Factors associated with poor overall survival(OS) were alpha-fetoprotein > 400 ng/m L, tumor size ≥ 5 cm, and high EP1 receptor expression, but not high COX-2 expression. Disease-free survival was not significantly different between patients with low or high levels of COX-2 or EP1. COX-2 immunoreactivity was significantly higher in well-differentiated HCC tissues(Edmondson grade Ⅰ-Ⅱ) than in poorly differentiated tissues(Edmondson grade Ⅲ-Ⅳ)(P = 0.003). EP1 receptor immunoreactivity was significantly higher in poorly differentiated tissue than in well-differentiated tissue(P = 0.001).CONCLUSION COX-2 expression appears to be linked to early HCC events(initiation), while EP1 receptor expression may participate in tumor progression and predict survival.

Effect of c-fos antisense probe on prostaglandin E_2-induced upregulation of vascular endothelial growth factor mRNA in human liver cancer cells

AIM: To examine the effect of prostaglandin E2 (PGE2) on the expression of vascular endothelial growth factor (VEGF) mRNA in the human hepatocellular carcinoma (HCC) HepG2 cells and the possible involvement of c-fos protein in this process.METHODS: Human HCC HepG2 cells were divided into three groups treated respectively with PGE2, a combination of PGE2 and c-fos antisense oligodeoxynucleotide (ASO),and PGE2 plus c-fos sense oligodeoxynudeotide (SO). The expression of VEGF mRNA in HepG2 cells after different treatments was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The relative expression level of VEGF mRNA in HepG2 cells in each group was measured.RESULTS: Administration of PGE2 resulted in an increased expression of c-fosand VEGF mRNA in HepG2 cells. The relative expression level of c-fos mRNA reached the peak at 3 h (68.4±4.7%) after PGE2 treatment, which was significantly higher than that at 0 h (20.6±1.7%, P＜0.01).Whereas, the highest expression level of VEGF mRNA was observed at 6 h (100.5±6.1%) after PGE2 treatment, which was significantly higher than that at 0 h (33.2±2.4%,P＜0.01). C-fos ASO significantly reduced PGE2-induced VEGF mRNA expression in HepG2 cells.CONCLUSION: PGE2 increases the expression and secretion of VEGF in HCC cells by activating the transcription factor c-fos, promotes the angiogenesis of HCC and plays an important role in the pathogenesis of liver cancer.

Association between the levels of prostaglandin E2 in tears and severity of dry eye

AIM: To investigate the relationship between the levels of prostaglandin E2(PGE2) in tears and dry eye disease severity based on both clinical symptoms and signs.METHODS: Tear samples were collected from 36 non-Sj?gren syndrome dry eye patients(10 males and 26 females, mean age 50.11±11.17 y). All participants completed the Ocular Surface Disease Index(OSDI) questionnaire and underwent a detailed ophthalmic examination including, tear film breakup time(TBUT), ocular surface fluorescein staining, Schirmer I test, and meibomian gland assessment. The level of PGE2 in tears was measured using enzyme-linked immunosorbent assay(ELISA). The independent associations between tear PGE2 levels and other variables including demographics, OSDI scores, TBUT, Schirmer scores, ocular surface staining scores, and stage of meibomian gland dysfunction(MGD) were evaluated using linear regression analysis. RESULTS: The mean PGE2 level in tears of dry eye patients was 537.85±234.02 pg/mL. The tear PGE2 levels significantly positively correlated with OSDI scores(R=0.608, P<0.001), however, they did not significantly associate with TBUT(R=0.153, P=0.373), Schirmer scores(R=-0.098, P=0.570), ocular surface staining scores(R=0.282, P=0.095), and stage of MGD(R=-0.107, P=0.535).Male sex was significantly negatively correlated with tear PGE2 levels.CONCLUSION: The levels of PGE2 in tears are positively correlated with dry eye symptoms. However, no significant association was found between tear PGE2 levels and the results of other common dry eye diagnostic tests.

Effect of lipopolysaccharide on diarrhea and gastrointestinal transit in mice: Roles of nitric oxide and prostaglandin E_2

AIM: To investigate the effect of lipopolysaccharide (LPS)on the diarrheogenic activity, gastrointestinal transit (GIT),and intestinal fluid content and the possible role of nitric oxide (NO) and prostaglandin E2 (PGE2) in gastrointestinal functions of endotoxin-treated mice.METHODS: Diarrheogic activity, GIT, and intestinal fluid content as well as nitric oxide and PGE2 products were measured after intraperitoneal administration of LPS in mice.RESULTS: LPS dose-dependently accumulated abundant fluid into the small intestine, induced diarrhea, but decreased the GIT. Both nitric oxide and PGE2 were found to increase in LPS-treated mice. Western blot analysis indicated that LPS significantly induced the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 in mice intestines. Pretreatment with NG-nitro-L-arginine-methyl ester (L-NAME, a non-selective NOS inhibitor) or indomethacin (an inhibitor of prostaglandin synthesis) significantly attenuated the effects of LPS on the diarrheogenic activity and intestine content, but reversed the GIT.CONCLUSION: The present study suggests that the pathogenesis of LPS treatment may mediate the stimulatory effect of LPS on nitric oxide and PGE2 production and NO/prostaglandin pathway may play an important role on gastrointestinal function.

血清PGE-2、B/A预测急性非静脉曲张性上消化道出血患者预后的价值

目的 探讨急性非静脉曲张性上消化道出血(ANVUGIB)患者预后的影响因素及血清前列腺素E-2(PGE-2)、血尿素氮与清蛋白(B/A)比值预测其预后的价值。方法 回顾性分析2018年1月至2022年1月武汉市中心医院消化内科收治的150例ANVUGIB患者的临床资料,比较死亡组(17例)及存活组(133例)患者一般资料,包含年龄、性别、既往上消化道出血史、平均动脉压、脉率、血红蛋白、清蛋白、血尿素氮、B/A比值、血糖、出血原因、出血次数、Rockall分数、血清PGE-2、血乳酸等,采用单因素和多因素logistic回归研究影响ANVUGIB患者预后的因素,并采用受试者工作特征(ROC)曲线分析血清PGE-2、B/A比值预测患者预后的价值。结果 B/A比值、Rockall分数、出血次数、血清PGE-2、血乳酸均为ANVUGIB患者死亡的相关因素,其中B/A比值、血清PGE-2均为ANVUGIB患者死亡的影响因素,差异均有统计学意义(P<0.05)。血清PGE-2、B/A比值,以及二者联合预测ANVUGIB患者预后的ROC曲线下面积分别为0.877、0.887、0.966。结论 血清PGE-2、B/A比值为影响ANVUGIB患者预后的危险因素,二者联合预测ANVUGIB患者预后具有良好的应用价值,在疾病诊断时临床医师可根据患者各项指标状况进行合理判断。

不同吸氧浓度对慢性阻塞性肺疾病大鼠环加氧酶2/前列腺素/E-前列腺素类激素信号通路及上皮细胞活性的作用机制

目的:探究不同吸氧浓度对慢性阻塞性肺病(COPD)大鼠环加氧酶2(COX-2)/前列腺素(PGE)/E-前列腺素类激素(EP)信号通路及上皮细胞活性的作用机制。方法:将大鼠随机分为正常对照组、COPD组、50%O_(2)组、70%O_(2)组、90%O_(2)组。检测大鼠肺功能;ELISA法检测肺泡灌洗液(BALF)中PGE2、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)水平;计算巨噬细胞、中性粒细胞和淋巴细胞百分比;H-E染色观察肺组织病理学变化;免疫印迹检测肺组织中COX-2、EP1、EP4蛋白表达。将BEAS-2B细胞分为对照组、香烟烟雾提取物(CSE)组、50%O_(2)组、70%O_(2)组、90%O_(2)组,CCK-8法和流式细胞仪检测BEAS-2B细胞增殖和凋亡能力。结果:与正常对照组相比,COPD组大鼠肺功能指标吸气阻力(RI)、肺总量(TLC)均增加,50 ms用力呼气量(FEV_(50))/用力肺活量(FVC)比值明显降低;与COPD组相比,50%O_(2)组和70%O_(2)组大鼠肺功能指标TLC、RI均明显降低,FEV_(50)/FVC比值明显升高,且70%O_(2)组肺功能指标变化最显著;与COPD组相比,90%O_(2)组大鼠肺功能指标TLC、RI均明显增加,FEV_(50)/FVC比值明显降低。与正常对照组相比,COPD组大鼠BALF中IL-6、IL-8、TNF-α、PGE2水平、白细胞总数及单核-巨噬细胞、淋巴细胞、中性粒细胞比例均明显升高;与COPD组相比,50%O_(2)组和70%O_(2)组大鼠BALF中IL-6、IL-8、TNF-α、PGE2水平、白细胞总数及单核-巨噬细胞、淋巴细胞、中性粒细胞比例均明显降低,且70%O_(2)组降低最显著;与COPD组相比,90%O_(2)组大鼠BALF中IL-6、IL-8、TNF-α、PGE2水平、白细胞总数及单核-巨噬细胞、淋巴细胞、中性粒细胞比例明显升高。与正常对照组相比,COPD组大鼠肺组织中COX-2、EP1、EP4蛋白表达均明显增加;50%O_(2)组和70%O_(2)组大鼠肺组织中COX-2、EP1、EP4蛋白表达明显低于COPD组;与COPD组相比,90%O_(2)组大鼠肺组织中COX-2、EP1、EP4蛋白表达均明显增加。CSE组BEAS-2B细胞活力低于对照组,细胞凋亡率高于对照组;与CSE组相比,50%组和70%组BEAS-2B细胞活力均明显增加,细胞凋亡率明显降低;与CSE组相比,90%组BEAS-2B细胞活力明显降低,细胞凋亡率明显增加。结论:COPD大鼠在氧疗浓度为50%和70%时可抑制COX-2/PEG2/EP信号通路的激活,改善COPD大鼠肺功能,减轻肺部炎症浸润,增加上皮细胞活性,且70%浓度氧疗效果最好;但氧疗浓度为90%时会加重COPD大鼠肺部炎症浸润,降低上皮细胞活性,促进COX-2/PEG2/EP信号通路的激活。

Expression of prostaglandin E_2 receptors in rat hippocampus

BACKGROUND: Prostaglandin E2 (PGE2) can directly regulate toxic injury of hippocampal neurons through participation by its receptor. Increase of excitability of hippocampal membrane and long-term synaptic elasticity are closely related to PGE2, PGD2 and PGF2A. This suggests that PGE2 may be a key molecule of neuronal signal passage and regulate the existence of neurons through its receptor. However, which isoforms of PGE2 receptor expressing in hippocampal neurons is still unclear. OBJECTIVE: To research the subtype expression of PGE2 receptor in hippocampus of rats through mRNA transcription and protein interpretation. DESIGN: Animal studies with random, control and operator and designer double-blind methods. SETTING: University of South Carolina, Animal Center. MATERIALS: Sprague-Dawley rats, aged 12 weeks, weighing 200 g, females 48 and males 48, were selected from Animal Center in South Carolina University. Tri ReagentTM kit was provided by Molecular Research Center, USA. METHODS: The experiment was carried out in Animal Center in South Carolina University from January to December 2005. The expression of the PGE2 receptors was profiled and compared in rat hippocampus using real-time RT-PCR and Western-blot techniques. MAIN OUTCOME MEASURES: Expression of PGE2 receptors in various isoforms of hippocampal neurons of rats. RESULTS: mRNAs of all four EP1-4 subtypes were detected in the hippocampus. Western-blot data showed consistently detectable bands at approximately Mr 50 000 of EP1, Mr 40 000 and Mr 52 000 of EP2, Mr 45 000, Mr 57 000 and Mr 105 000 of EP3, and Mr 46 000 of EP4. CONCLUSION: Identifying four subtypes of EPs heterogeneously expresses in the hippocampus.

A Case Report of Oseoid Osteoma in the Ulnar Cortex of the Distarl Radius Extending into the Distal Radioulnal Joint<br>—COX-2 Produced Prostaglandin E2 Possible Case of the Symptoms<br>

An 18-year-old girl presented with an osteoid osteoma in the ulnar side of the cortex of the distal radius extending into the distal radioulnar joint. The osteoid osteoma was removed from the distal radius at surgery. The patient’s symptoms were dramatically improved the day after surgery. A high concentration of prostaglandin E2 (PGE2) was seen in the joint and surrounding soft tissues, and cyclooxygenase-2 (COX-2) receptors were stained in the joint capsule and synovium inside the joint. This case report is the first to describe the concentration of PGE2 and stained COX-2 receptors in an osteoid osteoma in the ulnar cortex of the distal radius extending into the distal radioulnar joint.

INHIBITORY EFFECT OF ELECTROACUPUNCTURE ON FEVER INDUCED BY LIPOPOLYSACCHARIDE, INTERLEUKIN-1βAND PROSTAGLANDIN E_2 IN RATS

The effect of electroacupuncture (EA) on fever induced by either lipopolysaccharide (LPS), Interleukin-1β(IL-1β) or Prostaglandin E2(PGE2 ) was examined in SD rats in this study. EA stimulation (successive stimulation output; voltage intensity, 1 to 4 V; frequency, 1 Hz) was applied to bilateral equvalent Quchi (LI 11 ) acupoints for 30 min. Intraperitoneal injection of LPS (0111: B 4) at a single dose of 100 μg/kg caused high rectal temperature in rats, which was remarably sup pressed by EA either given simultaneously or 2 h after LPS injection. No difference in reduction of fever was found between two groups of rats treated by EA at different times. The rats that received adIninistration of hrIL-1β(2ng) or PGE2(3μg) into the prooptic area (POA) developed the acute and high fevers. The temperature in both cases was significantly decreased after EA stimulation. EA also partially inhibited the fever caused by intravenous injection of 0. 5μg/kg IL-1β. The they temperature increased within 1℃ in the rats that got intravenous injection of PGE2 (1. 5mg/kg), and EA did not present strong inhibitory effect on it. The present results demonstrate that EA possesses an antipyretic effect in rats and suggest that which may attribute to the suppression of the actions of IL-1β and/or PGE2 in the development of fever.

Relationship of cyclic stretching of human patellar tendon fibroblasts with abnormal increase of prostaglandins E2 and leukotriene B4

To investigate the relationship between tendinopathy and higher production of prostaglandins E2 (PGE2) and leukotriene B4(LTB4) induced by cyclic stretching of human patellar tendon fibroblasts.Methods We used a novel in vitro model system to mimic in vivo conditions,where human patellar tendon fibroblasts (HPTFs) were uniaxially stretched with different magnitudes of stretching (4%,8% and 12%).Non-stretched fibroblasts were used as control.The productions of PGE2 and LTB4 as well as the expression of cycloxygenase (COX) and 5-lipoxygenase (5-LO) were then measured every four hours of cyclic stretching.In addition,we treated the cells with inhibitors of COX or 5-LO.Results It was found that cyclic stretching of fibroblasts at 8% and 12% of stretching increased PGE2 and LTB4 levels.Blocking the COX enzyme with indomethacin (25 mol/L) decreased PGE2 levels but increased LTB4 production and vice versa.Whereas decreasing LTB4 production with MK-886 (10 μmol/L) could increase PGE2 levels compared to cells tretched without inhibitors.Conclusion Cyclic stretching of HPTFs produces high levels of PGE2 and LTB4,where a balance exists:blocking PGE2 production increases the production of LTB4,and vice versa.Therefore,this study raises the possibility that the routine use of COX inhibitors in clinical treatment of tendinopathy may exacerbate the condition by causing neutrophil-mediated inflammatory and degenerative changes in the tendon due to increased levels of LTB4,which is a potent chemoattractant for neutrophils.17 refs,3 figs.

牙周炎患者血清中内脂素和PGE2水平检测及其与牙周炎活动性的关系

目的:检测牙周炎患者血清中内脂素、前列腺素E2(PGE2)和白细胞介素1β(IL-1β)的水平,探讨内脂素和PGE2在慢性牙周炎发病中的作用及其对于牙周炎活动性评估的临床意义。方法:选取79例慢性牙周炎患者作为慢性牙周炎组,根据慢性牙周炎活动期的诊断标准将患者分为慢性牙周炎活动期组(33例)和慢性牙周炎静止期组(46例);另选取健康志愿者25例作为健康对照组。收集各组研究对象的血清,采用ELISA法定量检测各组研究对象血清中内脂素、PGE2和IL-1β水平,采用Spearman分析和偏相关分析检测各组研究对象血清中内脂素水平与PGE2、IL-1β水平的相关性。结果:慢性牙周炎组患者血清中内脂素、PGE2和IL-1β水平均明显高于健康对照组(P<0.05);慢性牙周炎活动期组患者血清中内脂素、PGE2和IL-1β水平高于慢性牙周炎静止期组(P<0.05)。相关性分析,慢性牙周炎组患者血清中内脂素与IL-1β水平(r=0.68,P<0.05)、IL-1β与PGE2水平(r=0.79,P<0.05)、内脂素与PGE2水平(r=0.63,P<0.05)呈正相关关系;患者血清中内脂素水平越高,PGE2水平越高。慢性牙周炎活动期组患者血清中内脂素与PGE2水平呈显著正相关关系(r=0.78,P<0.05),而慢性牙周炎静止期组患者血清中内脂素与PGE2水平则呈低度正相关关系(r=0.45,P<0.05)。结论:内脂素和PGE2可能共同参与了牙周炎的发生发展过程。血清中内脂素和PGE2水平升高可能预示着牙周炎处于活动期。