幽门螺杆菌感染与胃粘膜环氧化酶-2表达的关系

环氧化酶(COX)是合成前列腺素的限速酶。该酶有两种异构体，即COX-1和COX-2。最近研究显示，COX-2表达与胃肠道肿瘤的发生有关。幽门螺杆菌(Hp)感染是慢性活动性胃炎的主要病因，也是胃癌发生的危险因素。2000～2001年，我们对97例胃病患者进行了Hp及胃粘膜COX-2检测，旨在探讨Hp感染与胃粘膜COX-2表达的关系。     

胃损伤愈合过程中环氧化酶-2的表达及其作用

目的：探讨环氧化酶－2（COX－2）在胃粘膜的表达，和特异性COX－2抑制剂对胃粘膜损伤愈合的影响。方法：1、大鼠禁食24h，经胃管胃内投入0.6mol/L HCl 1ml。应用免疫印渍分析盐酸投入前、后胃粘膜COX－1和COX－2表达水平。2、盐酸投入后10min，胃内给予COX－2抑制剂NS－398，剂量为0.4mg/kg,4mg/kg和40mg/kg，盐酸投入前和盐酸投入后1h,3h,6h,12h,24h和48h，分别处死大鼠，剖腹取胃，观测胃粘膜损伤的愈合情况。结果：1、盐酸致胃粘膜损伤后，COX－2表达增加而COX－1表达无显变化。2、盐酸所致胃粘膜损伤后对照组在48h内愈合，而NS－398组呈剂量依赖性地延迟胃粘膜损伤的愈合，两组相比有显差异（P＜0．05）。结论：COX－2的表达在胃粘膜损伤愈合过程中起重要作用。     

幽门螺杆菌感染所致胃粘膜上皮细胞凋亡与p53和bcl-2表达的关系

目的阐明幽门螺杆菌(Helicobacter pylori,Hp)感染对胃粘膜上皮细胞凋亡的作用及其与 p53和 bc(?)-2表达的关系。方法本研究观察了28例幽门螺杆菌 Hp 阳性和17例 Hp 阴性慢性浅表性胃炎患者和20例 Hp 阴性正常胃粘膜对照者胃粘膜上皮细胞凋亡百分率及其 p53和bc(?)-2表达水平。结果:正常胃粘膜和 Hp 阴性慢性浅表性胃炎患者胃粘膜上皮细胞凋亡百分率低,p53蛋白低表达和 bc(?)-2蛋白高表达。而 Hp阳性慢性浅表性胃炎患者胃粘膜上皮细胞凋亡百分率高,p53蛋白高表达而 bc(?)-2蛋白低表达。结论 Hp 可诱导胃粘膜上皮细胞凋亡,其作用途径与上调 p53蛋白表达水平及下调 bc(?)-2蛋白表达水平有关。     

幽门螺杆菌诱导胃粘膜上皮细胞凋亡与Bax蛋白的表达

目的 观察幽门螺杆菌(Hp)感染诱导胃粘膜上皮细胞凋亡与Bax蛋白表达的关系,探讨Hp诱导胃粘膜上皮细胞凋亡的机制.方法 采用脱氧核糖核酸末端转移酶介导的缺口末端标记(TUNEL)技术原位观察和比较73例慢性胃炎患者胃粘膜上皮细胞凋亡情况,对其中50例Hp阳性患者Hp根除前后胃粘膜上皮细胞凋亡的变化进行检测;并采用免疫组织化学染色检测Bax蛋白表达变化.结果 Hp阳性患者胃粘膜上皮细胞凋亡指数为12.8%,明显高于Hp阴性者(3.6%)(t=6.64,P＜0.01);Hp根除后胃粘膜上皮细胞凋亡指数(4.4%)较治疗前明显降低(12.5%,t=5.39,P＜0.01),而持续阳性者凋亡指数无明显降低.Hp阳性患者胃粘膜上皮细胞Bax蛋白表达率为62.3%,显著高于Hp阴性者(35.0%,χ2=4.36,P＜0.05);Bax蛋白表达阳性的Hp阳性患者在Hp根除后Bax阳性细胞密度显著减少(t=3.18,P＜0.01),而Hp未被根除者Bax阳性细胞密度无明显变化.结论 Hp感染可诱导胃粘膜上皮细胞凋亡,这可能是Hp参与胃癌发生的重要机制之一;Hp感染可促进Bax蛋白表达增加,这可能是Hp感染诱导胃粘膜上皮细胞凋亡的机制之一.     

Hp-cagA感染与胃癌环氧化酶Ⅱ表达的相关性研究

目的：观察胃癌组织中COX－2的表达情况，探讨Hp-cagA菌株感染与胃癌COX－2表达之间的关系，为胃癌的早期预防提供有价值的实验和理论依据。方法：采用流式细胞术，定量检测及分析32例胃癌组织及相应的癌旁正常胃组织中COX－2的表达水平，并通过PCR技术对胃癌组织中cagA基因的扩增产物进行检测。结果：32例胃癌组织中，有27例COX－2过表达，19例cagA阳性的胃癌组织中COX－2的表达水平明显高于13例cagA阴性的胃癌组织。结论：COX－2在胃癌组织中过度表达，cagA菌株感染可上调胃癌组织中COX－2的过度表达。可能存在cagA菌株感染之外的其它因素或机制调节COX－2的表达。因此，在根治幼感染的同时，应用COX－2特异性抑制剂可能是一种有效预防胃癌发生、发展的新路。     

幽门螺杆菌感染对胃粘膜增殖活性的影响

目的观察幽门螺杆菌（Hp）感染与胃粘膜增殖活性的关系．方法慢性胃炎活检标本68例，用W－S银染法、0．25％复红法和HpDNAPCR技术检测Hp，用免疫组化法观察增殖细胞核抗原（PCNA），C-erb-B2和p53基因的表达，按标准化方案对核仁组成区嗜银蛋白（AgNOR）颗粒计数．结果Hp阳性组（30例）和阴性组（38例）中InyNAⅠ，Ⅱ，Ⅲ，Ⅳ级分别为5，7，4，14例和27，11，0，0例，AgNOR计数分别为3．44±1.20个和1．08±0．08个，差异有显著性（P＜0．05）．Hp阳性组中有4例C-erb-B2在新生腺体和不全肠化柱状细胞中局部阳性，Hp阴性组中未见阳性表达结论Hp感染时胃粘膜增殖活性增强，这可能是胃癌发生的高危因素之一．     

慢性肝病胃粘膜乙型肝炎病毒表达及幽门螺杆菌感染

目的 探讨乙型肝炎病毒（HBV）的泛嗜性及与幽门螺杆菌（Hp）感染的关系。方法选择慢性乙型肝炎（慢肝）28例、乙型肝炎后肝硬化（肝硬化）44例,共72例作为观察组,无肝病的胃病患者30例作为对照组。受检者常规胃镜检查,取胃窦幽门周围3cm以内活体组织3块,除普通病理检查外,分别做乙型肝炎病毒表面抗原（HBsAg）、乙型肝炎病毒核心抗原（HBcAg）检测及快速尿素酶、品红染色和免疫组化法检测Hp。结果 慢肝组有不同程度的胃粘膜慢性炎症者达92.9％（26/28）、肝硬化组达95.5％（42/44）,其中慢肝组以单纯慢性炎症为多,而肝硬化组以伴萎缩和肠化者为多。72例慢性肝病者中有51例胃粘膜HBV阳性,其中HBsAg、HBcAg双阳性16例;肝硬化组HBV抗原表达高于慢肝组,而HBsAg、HBcAg双阳性者低于慢肝组（P均<0.05）。在慢肝和肝硬化组有炎症的胃粘膜中Hp阳性率分别为76.9％（20/26）、69.0％（29/42）,与对照组相比无显著差别。慢性肝病Hp阳性、阴性者胃粘膜HBV抗原表达率分别为69.8％（37/53）、73.7％（14/19）,亦无统计学差异（P>0.05）。结论 （1）HBV在慢肝及肝硬化患者胃粘膜表达明显,应重视其在胃粘膜病变中的作用,加强防护措施。（2）在胃粘膜中HBV与Hp表达未见相关关系。     

61例小儿内镜检查结果及其与Hp感染关系分析

目的为探讨内镜检查对小儿上消化道疾病症因诊断价值及幽门螺杆菌（Hp）感染的临床意义.方法应用OlympasGIF-Q10型纤维内缓、GIF-rQ230型电子内镜对61例有反复上腹痛、消化不良及黑便等症状的患儿行内镜检查，对其中30例慢性残表性胃炎及消化性溃疡的患儿进行胃粘膜活检作病理学Hp检查及快速尿素酶试验.结果61例患儿内镜及清理检查结果：慢性浅表性胃炎33例．胃溃疡1例，复合性溃疡1例，十二指肠球部溃疡9例，十二指肠球部息肉1例，慢性残表性胃炎伴食管下段炎、贲门炎2例,胃粘膜脱垂并胃炎3例，食管异物1例，球部蛔虫1例.11例消化性溃疡患儿病理切片查见Hp及尿素酶试验均为阳性，19例慢性残表性胃炎胃粘膜病理切片查见Hp及尿素酶试验均为阳性，19例慢性发表性胃炎胃粘膜病理切片查见Hp16例,快速尿素酶试验阳性17例，平均Hp感染率为90％，所有有Hp感染的患儿均经快速抗Hp等治愈.结论小儿内镜检查安全、方便，是小儿上消化道疾病病因诊断最准确的方法.有反复上腹痛、消化不良等上消化道症状者．提示Hp感染达90％，快速抗Hp治疗可收良效     

胃粘膜淋巴滤泡与幽门螺杆菌关系探讨

目的 探讨含有细胞毒素相关基因A（cagA)菌株感染与胃粘膜淋巴滤泡形成之间的关系，并对胃粘膜淋巴滤泡的发生与幽门螺杆菌（Hp）感染状况的关系等进行观察。方法 对655例慢性胃炎，消化性溃疡的患者进行胃镜检查，取胃窦 粘膜组织作Hp检测和组织病理检查，并选择70份Hp培养阳性的临床分离菌，用PCR扩增法进行cagA基因的检测。结果 Hp感染患者中胃粘膜淋巴滤泡的发生率（60.14%)显著高于非Hp感染者（17.06%)；胃粘膜淋巴滤泡在活动性胃炎比非活动性胃炎中更易检测到；在Hp相关性胃肠病中，慢性胃炎、胃溃疡、地下二指肠球溃这三者之间胃粘膜淋巴滤泡的发生率无显著性差异。结论 胃粘膜淋巴滤泡的发生直接与Hp感染相关， 并可作为一种Hp感染相关性胃肠病中一个较为恒定的形态特征；Hp作为一种抗原刺激胃粘膜产生淋巴滤泡的作用与Hp菌株的毒力（cagA基因）无关。     

IL-8、TNF-α在Hp感染中的作用研究

目的 研究幽门螺杆菌（Hp)相关性胃肠疾病时胃粘膜组织IL-8、TNF-α的活性水平及其病理作用。方法 采用酶联免疫吸附试验夹心法检测胃粘膜组织中IL-8、TNF-α的水平，并观察IL-8、TNF-α水平与胃粘膜炎症活动的关系。结果 1、Hp感染的胃粘膜组织中，IL-8或TNF-α的浓度明显高于非Hp感染患者。2、IL-8、TNF=α在Hp相关性胃与十二指肠球溃怕患者胃粘膜组织的表达无显著性差异。3、在Hp感染患者中，有炎症活动的患者其胃粘膜组织中IL-8、TNF-α的表达明显高于无炎症活动的患者。4、Hp感染患者胃粘膜组织中IL-8的表达与TNF-α水平呈正相关。结论 炎性细胞因子IL-8、TNF-α在Hp相关性胃十二指肠疾病的发病过程中可能起致病作用。     

Roles of Helicobacter pylori infection and cyclooxygenase-2 expression in gastric carcinogenesis

AIM: Cyclooxygenase (COX)-2 is over expressed in gastrointestinal neoplasm. Helicobacter pylori (H pylori) infection is causally linked to gastric cancer. However, the expression of COX-2 in various stages of H pylori-associated gastric carcinogenesis pathway has not been elucidated. Therefore, the aim of this study was to clarify the role of H pylori induced COX-2 expression during carcinogenesis in the stomach. METHODS: Gastric biopsies from 138 subjects (30 cases of chronic superficial gastritis (CSG), 28 cases of gastric glandular atrophy (GA), 45 cases of gastric mucosal intestinal metaplasia (IM), 12 cases of moderate gastric epithelial dysplasia and 23 cases of gastric cancer) were enrolled. H pylori infection was assessed by a rapid urease test and histological examination (modified Giemsa staining). The expression of COX-1 and COX-2 in human gastric mucosa was detected by immunohistochemical staining. RESULTS: H pylori infection rate was 64.3% in GA and 69.5% in gastric cancer, which was significantly higher than that (36.7%) in CSG (P<0.05). The positive expression rates of COX-2 were 10.0%, 35.7%, 37.8%, 41.7% and 69.5% in CSG, GA, IM, dysplasia and gastric cancer, respectively. From CSG to GA, IM, dysplasia and finally to gastric cancer, expression of COX-2 showed an ascending tendency, whereas COX-1 expression did not change significantly in the gastric mucosa. The level of COX-2 expression in IM and dysplasia was significantly higher in H pylori-positive than in H pylori-negative subjects (P<0.01). CONCLUSION: COX-2 expression induced by H pylori infection is a relatively early event during carcinogenesis in the stomach.     

幽门螺杆菌感染胃黏膜病变基因表达和细胞生物学行为

目的　研究幽门螺杆菌(Helicobacterpylori,Hp)感染胃黏膜病变的多基因表达和细胞生物学行为。方法　327例患者经胃镜及手术的胃黏膜病变标本,应用免疫组化染色法,检测p53、p16、bcl-2和环氧合酶同工酶-2(COX-2)蛋白的表达。Hp感染由快速尿素酶试验结合组织学检查/     

Expression of COX-2 proteins in gastric mucosal lesions

AIM: To investigate the expression of COX-2 proteins in gastric mucosal lesions and to assess the relationship between COX-2 expression and type, pathologic stage, differentiation, or lymph node metastasis in gastric cancer and the relationship between COX-2 expression and H pylori infection in gastric mucosal lesions. METHODS: Thirty patients with gastric carcinoma underwent surgical resection. Samples were taken from tumor site and paracancerous tissues, and ABC immunohistochemical staining was used to detect the expression of COX-2 proteins. H pylori was determined by rapid urea test combined with pathological stating/14C urea breath test. RESULTS: The positive rate and staining intensity of mutant COX-2 gene expression in gastric cancer were significantly higher than those in paracancerous tissues (66.7% vs 26.7%) (P<0.01, P<0.001). There was a significant correlation between COX-2 and pathologic stage or lymph node metastasis type of gastric carcinoma (76.0% vs 20.0%, 79.2% vs 16.7%) (P<0.05). No correlation was found between COX-2 expression and type or grade of differentiation (P>0.05). COX-2 expression of intestinal metaplasia (IM) or dysplasia (DYS) with positive H pylori was significantly higher than that with negative H pylori (50.6% vs 18.1%, 60.0% vs 33.3%) (P<0.05). CONCLUSION: COX-2 overexpression was found in a large proportion of gastric cancer tissues compared with matched non-cancerous tissues and was significantly associated with advanced tumor stage and lymph node metastasis. Overexpression of COX-2 plays an important role in tumor progression of gastric cancer. COX-2 may also play a role in the early development/promotion of gastric carcinoma and is associated with H pylori infection.     

Cyclooxygenase-2 expression in gastric antral mucosa before and after eradication of Helicobacter pylori infection

OBJECTIVE: Helicobacter pylori (H. pylori) causes chronic gastritis. The inducible prostaglandin synthetase cyclooxygenase 2 (COX-2) plays an important role in inflammatory conditions. We hypothesized that H. pylori-associated chronic gastritis would express COX-2 protein. Our aim was to evaluate the effect of eradication of H. pylori infection on COX-2 expression in the antral mucosa of patients before and after antibiotic therapy. METHODS: Tissues were obtained from patients with non-ulcer dyspepia undergoing H. pylori eradication. Ten patients with proven H. pylori infection and subsequent successful eradication were studied. Three biopsies of antral mucosa were evaluated before and after H. pylori eradication. The amount of acute and chronic inflammation was quantitated. Immunohistochemical staining for COX-2 was expressed as a percentage of the total number of cells and correlated with the degree of chronic inflammation. RESULTS: Specific immunostaining for COX-2 was observed in antral mucosa of patients infected with H. pylori. Patchy cytoplasmic staining was seen in surface epithelial cells and strong cytoplasmic staining for COX-2 was seen in parietal cells. Spotty cytoplasmic staining for COX-2 was also seen in lamina propria plasma cells, as well as there being macrophages present in the germinal centers of lymphoid aggregates. COX-2 expression could be detected both before and after eradication of H. pylori. The mean percentage of cells staining for COX-2 was significantly higher in H. pylori-infected mucosa, compared with mucosa after successful H. pylori eradication (33.4% +/- 5.4 vs 18.9% +/- 3.3, p = 0.038). COX-2 immunostaining correlated best with the chronic inflammation score (r2 = 0.78, p < 0.001). There was a strong correlation for those subjects who were H. pylori infected, as well as for those who had successful H. pylori eradication. CONCLUSIONS: H. pylori associated acute and chronic antral inflammation was associated with immunohistochemical detection of COX-2 protein in epithelial cells, in addition to associated mononuclear cells and parietal cells. Expression was reduced, but not eliminated, in the epithelium after successful eradication of H. pylori. Despite the reduction in COX-2 expression after H. pylori eradication, expression of COX-2 in epithelial cells remained and strongly correlated with the extent of the chronic inflammatory cell infiltrate. The clinical implications of H. pylori-associated induction of COX-2 expression for patients on selective COX-2 inhibitors, in addition to the role of COX-2 in gastric carcinogenesis, deserve further study.     

Gastric MALT-lymphoma,gastrin and cyclooxygenases

Malt-lymphoma, gastrin and COX-2 interaction. Low grade, mucosal associated lymphoid tissue (MALT)-lymphoma is an unique among gastric malignancies where causal involvement of Helicobacter pylori (H. pylori) infection has been proposed based on complete regression of the tumor following the eradication therapy. In this report ten primary, low-grade MALT-lymphomas have been examined before and 6 months after one week of successful eradication therapy (clarithromycin + amoxicillin + omeprazole). Gastric biopsy samples from tumor and intact antrum and corpus mucosa were obtained during endoscopy before and after eradication for assessment of expression of gastrin and gastrin receptor (CCKB-R) as well as cyclooxygenase (COX)-1 and COX-2 using RT-PCR. The gastric lumen and serum gastrin and mucosal and tumor tissue PGE2 biosynthesis were determined by RIA before and after H. pylori eradication. Eradication of H. pylori resulted in complete endoscopic and histological remission of MALT-lymphoma in 9 out of 10 patients as assessed 6 months after this eradication. Before eradication, the mRNA expression for gastrin and CCKB-R as well as mRNA expression for COX-1 and COX-2 were observed in tumor tissue and infected mucosa, while corpus mucosa expressed only CCKB-R and antrum mucosa only gastrin. Six months upon the eradication when MALT-lymphoma completely regressed both endoscopically and histologically in 9 of 10 tested subjects, the expression of gastrin and COX-2 disappeared from the former area of MALT-lymphoma tumor. Gastrin mRNA remained detectable only in antrum mucosa, CCKB-R mRNA in corpus mucosa and COX-1 mRNA both in antrum and corpus mucosa. Gastric luminal and serum gastrin levels and gastric mucosa and tumor PGE2, which were greatly elevated before eradication, became normalized after this procedure. This study demonstrates that low-grade MALT-lymphoma is linked to H. pylori infection which may promote the expression and excessive release of gastrin and COX-2 expression that could be involved in the pathogenesis of MALT-lymphoma.     

Influences of Helicobacter pylori on cyclooxygenase-2 expression and prostaglandinE2 synthesis in rat gastric epithelial cells in vitro

BACKGROUND AND AIM: It is known that cyclooxygenase (COX)-2 is over expressed in gastrointestinal neoplasia and Helicobacter pylori (H. pylori) infection is causally linked to gastric cancer. The present study aimed to elucidate the effects of H. pylori on COX-2 expression and prostaglandinE(2) (PGE(2)) production in a gastric epithelial cell line derived from normal rat gastric mucosa (RGM1). METHOD: H. pylori water extracts were prepared from a supernatant of the H. pylori suspension in distilled water. RGM1 cells were cultured with H. pylori water extracts at the final concentration of 2.5, 5, 10 microg/mL for 24 h. For the time sequence study, RGM1 cells were cultured with 10 microg/mL H. pylori water extracts for 0, 6, 12, 24 and 48 h. COX-1 and COX-2 expression in the RGM1 cells was analyzed by western blotting. The levels of PGE(2) in the cultured media were measured by enzyme immunoassay. RESULTS: H. pylori did not affect COX-1 expression; whereas COX-2 expression increased by six-fold at 24 h after incubation of RGM1 cells with 10 microg/mL H. pylori water extracts. The increase in COX-2 expression was evident after 12 h of incubation; reached a peak at 24 h and declined at 48 h. H. pylori dose dependently increased COX-2 expression and PGE(2) synthesis in RGM1 cells. CONCLUSION: H. pylori induces COX-2 expression and increases PGE(2) synthesis in RGM1 cells in vitro. These results indicate that H. pylori-associated gastric carcinogenesis may depend on COX-2 expression.     

The interaction of H. pylori infection and NSAIDs in cyclooxygenase-2 mRNA expression in gastric antral, corpus mucosa, and gastric ulcer

BACKGROUND: Although Helicobacter pylori infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs) are the two major causes of gastric ulcer, their interaction remains controversial. We constructed a prospective cohort study to evaluate how these two factors influence the expression of COX-2 mRNA in gastric antral, corpus mucosa, and gastric ulcer. METHODS: Tissues were obtained by endoscopic biopsy of gastric antral, corpus mucosa, and gastric ulcer. The presence of H. pylori was determined by culture or histology using Giemsa stain. NSAID use was assessed by structured questionnaire and medical record review. The expression of COX-2 mRNA was detected by the TaqMan quantitative RT-PCR system. RESULTS: H. pylori infection was associated with increased COX-2 expression only in antral mucosa (0.77 +/- 0.13 vs. 0.31 +/- 0.07, P < 0.01). NSAID use was significantly associated with decreased COX-2 expression in ulcer (4.49 +/- 1.50 vs. 9.82 +/- 2.48, P < 0.05) but not in antral or corpus mucosa. Regarding the interaction between H. pylori and NSAID, we found that H. pylori infection was associated with increased COX-2 expression in antral mucosa for both NSAID users and nonusers. In NSAID users, H. pylori infection was not associated with increased COX-2 expression in ulcer edge. CONCLUSION: H. pylori infection was associated with increased COX-2 expression in gastric antral mucosa for both NSAID users and nonusers, but not in gastric ulcer, where the effect of NSAID inhibition plays a major role. With these observations, we can interpret indirectly that H. pylori eradication does not interfere with gastric ulcer healing in NSAID users.     

Influence of gastritis on cyclooxygenase-2 expression before and after eradication of Helicobacter pylori infection

OBJECTIVES: Helicobacter pylori infection causes chronic gastritis and induces cyclooxygenase (COX)-2 expression. The relationship between gastritis and COX-2 expression is not well understood, especially long after the organism has been eradicated. We designed a study to elucidate this relationship. METHODS: Four endoscopic gastric biopsies from each of 118 H. pylori-infected subjects were assessed for COX-2 expression immunohistochemically, gastritis, by an updated Sydney System. In the 107 successfully eradicated subjects, the assessment was repeated once yearly, for 3 years. RESULTS: After successful eradication, COX-2 expression was reduced significantly regardless of site. Atrophy improved significantly and intestinal metaplasia improved but not in the antrum greater curvature. After 1 year COX-2 expression was not significantly different in the epithelia with and without intestinal metaplasia. Correlation between COX-2 expression and neutrophil score in the antrum (r = 0.214, P = 0.042) and inflammation in the corpus (r = 0.234, P = 0.025) disappeared after eradication. COX-2 expression correlated well with atrophy and metaplasia before and after eradication. No significant reduction in COX-2 or improvement in gastritis was found in subjects with eradication failure. CONCLUSION: H. pylori infection is associated with the enhancement of COX-2 expression in the gastric mucosa. Eradication therapy reduces COX-2 expression and hence may reduce the risk of cancer development.