萎缩性胃炎患者幽门螺杆菌根除后表皮生长因子及其受体的变化

目的　研究幽门螺杆菌 (Helicobacterpylori,H .pylori)感染对胃黏膜表皮生长因子受体 (epidermalgrowthfactorreceptor ,EGFR)、血清表皮生长因子 (epidermalgrowthfactor,EGF)水平的影响。方法　对 60例H pylori检测阳性的慢性萎缩性胃炎患者进行根除治疗 ,在治疗前及疗程结束 3个月后分别进行胃镜检查 ,并采用免疫组化及放射免疫法测定H pylori根除前后胃黏膜EGFR和血清EGF含量。 3 0例H pylori检测阴性且胃镜检查无明显异常者作为正常对照组。结果　 60例H pylori检测阳性的CAG患者的胃黏膜EGFR阳性率及血清EGF水平均高于正常对照 ,其差异有显著性 (P <0 0 5 ,P <0 0 1)。有 3 1例在根除治疗 3个月后进行了复查 ,其中 2 4例H pylori得到成功根除。 2 4例H pylori得到根除的CAG患者 ,根除后血清EGF水平明显下降 (P <0 0 1) ,而EGFR阳性率无改变 (P >0 0 5 )。结论　H pylori感染引起胃黏膜EGFR阳性率及血清EGF水平增加 ,根除H pylori后血清EGF可恢复至正常水平 ,而胃黏膜EGFR阳性率在短期内没有明显改变     

幽门螺杆菌(Hp)感染与胃肠激素

目的了解Hp感染引起人体胃肠激素的变化,从而探讨其致病的机制.方法复习文献,分别综述各有关激素于Hp感染时的体内变化,及其与疾病和病生理的关系.结果发现10种胃肠激素于Hp感染时有研究资料,其中促胃液素最多,其次为生长抑素(SS),再其次为表皮生长因子、和转化生长因子,此外,尚有胰岛素、胰岛素样生长因子1、肠高糖素、缩胆囊素、和抑胃素等.这些激素于Hp感染时,大都有量的变化,根除Hp,即恢复;并不同程度地提示致病的机制.促胃液素释放肽是以胃功能兴奋剂来协助胃功能的研究,并未直接参与Hp感染的代谢.较主要的表现有Hp感染致SS减少,使促胃液素-SS平衡失调、高促胃液素血症、胃酸增高、十二指肠溃疡生成;胃表皮生长因子及其受体遭损伤,致溃疡形成和愈合困难;通过胰高糖素参与,致胃粘膜肠上皮化生等.结论Hp感染所致的诸多胃肠激素变化,提示此菌感染与胃病有关.     

幽门螺杆菌感染与胃液表皮生长因子关系的探讨

1材料和方法 1.1材料 1998/1999在我院进行检查的病例,溃疡组50例,男36例,女14例,平均年龄48岁±14岁(13岁～78岁),其中Hp阳性35例,阴性6例.对照组50例,男22例,女28例,平均年龄37岁±11岁(20岁～65岁).其中Hp阳性6例,阴性19例,无其他系统慢性感染性疾病.     

疣状胃炎与幽门螺杆菌,胃泌素和表皮生长因子等相关的研究

疣状胃炎（verrucousgastritis，VG）是指胃粘膜上形成脐窝状凹陷的隆起性病变，主要分布在胃窦部。本文测定了VG患者的胃液甘胆酸（GA、表皮生长因子（EGF）、pH值和血液胃泌素（Gas）、生长抑素（SS）值及胃窦粘膜的Hp、病理炎症分级，以探讨其发病的相关同素。材料与方法一、研究对象与标本采集（－一研究对象：经胃镜检查证实的疣状胃炎60例（病变均在胃窦，直径4～smm，个数1～15个），其中男52例，女8例，年龄为23～60岁，平均50岁；对照组为慢性浅表性胃炎（CSG）25例，其中男22例，女3例，年龄为18～58岁，平均45岁，无明显…     

幽门螺杆菌与胃黏膜bFGF,FGFR-2表达的关系及意义

目的:探讨幽门螺杆菌(H pylori)感染的胃黏膜上皮细胞碱性成纤维细胞生长因子(bFGF)、成纤维细胞生长因子受体-2 (FGFR-2)的表达及其在胃黏膜癌变过程中的意义.方法:选择慢性浅表性胃炎(CSG)30例、胃黏膜肠上皮化生(IM)29例、不典型增生(Dys) 31例及胃癌(GC)55例.采用免疫组化SP法检测胃黏膜上皮细胞bFGF,FGFR-2表达状况,用快速尿素酶试验和组织学Warthin-Starry嗜银染色法联合检测胃黏膜H pylori感染情况.结果:CSG组bFGF,FGFR-2的表达显著低于其余三组(IM组:χ~2=4.002,P<0.05;χ~2= 4.163,P<0.05;Dys组:χ~2=15.779,P=0.000;χ~2=15.949,P=0.000;GC组:χ~2=24.110,P= 0.000;χ~2=18.736,P=0.000),IM组的表达低于Dys组及GC组(Dys组:χ~2=4.258,P<0.05;χ~2 =4.212,P<0.05:GC组:χ~2=7.786,P<0.01;χ~2 =4.687,P<0.05),而Dys组与GC组间无显著性差异.H pylori阳性IM及Dys组bFGF,FGFR-2的表达均显著高于阴性组(IM组:χ~2=10.076,P<0.01;χ~2=7.535,P<0.01;Dys组:χ~2=11.501,P<0.01;χ~2=8.330,P<0.01).H pylori阳性Dys组bFGF,FGFR-2表达显著高于GC组(χ~2= 4.201,P<0.05;χ~2=3.982,P<0.05),H pylori阳性IM组则与GC组的表达无显著性差异;H pylori阴性Dys组及IM组bFGF的表达均显著低于GC组(χ~2=5.736,P<0.05;χ~2=17.113,P= 0.000),H pylori阴性Dys组FGFR-2表达与GC组无显著性差异而IM组的FGFR-2的表达显著低于GC组(χ~2=11.091,P<0.05).结论:H pylori感染引起胃黏膜上皮细胞bFGF及FGFR-2的过度表达可能与H pylori感染致胃黏膜上皮细胞的癌变有关.     

幽门螺杆菌感染与PCNA、TGF－α、EGFR表达的关系探讨

采用免疫组化标记链亲和素生物素法（ＬＳＡＢ）对幽门螺杆菌（ＨＰ）阳性和阴性胃粘膜的增殖细胞核抗原（ＰＣＮＡ）、转化生长因子α（ＴＧＦ－α）、表皮生长因子受体（ＥＧＦＲ）表达进行对比分析，结果表明ＨＰ阳性胃粘膜的ＰＣＮＡ、ＴＧＦ－α、ＥＧＦＲ表达显著高于ＨＰ阴性胃粘膜（Ｐ＜０．０５），且在不典型增生时达高峰。提示ＨＰ感染的胃粘膜处于高增殖状态，并可能通过刺激ＴＧＦ－α、ＥＧＦＲ过量表达而引起胃癌的发生。     

Decreased expression of epidermal growth factor receptor and mRNA of its ligands in Helicobacter pylori-infected gastric mucosa

BACKGROUND: Epidermal growth factor (EGF) and TGF-alpha play a central role in maintaining gastric mucosal integrity. Little is known about the regulative role of the four other widely expressed epidermal growth factor receptor ligands, heparin-binding EGF, amphiregulin, betacellulin and cripto in the gastric mucosa. METHODS: Nineteen patients with Helicobacter pylori-positive gastritis and 32 healthy controls were investigated. Mucosal mRNA expression of EGF receptor ligands was determined by quantitative PCR before and after H. pylori eradication. PCR products were analyzed by soft laser scanning densitometry. Moreover, the effect of chronic active gastritis on EGF receptor expression was assessed by [125I] EGF receptor autoradiography. Immunohistochemistry was performed for TGF-alpha to localize growth factor expression. RESULTS: Antral and oxyntic biopsies showed strong mRNA expressions for TGF-alpha, amphiregulin and heparin binding EGF, but not for EGF, cripto and betacellulin. mRNA expression was significantly reduced down to 50% in H. pylori infection, significantly lower compared to normal gastric mucosa, and increased after eradication therapy. Moreover, chronic gastritis was associated with decreased antral EGF receptor binding compared to healthy controls, possibly reflecting reduced autoinduction. Immunohistochemical analyses localized TGF-alpha in the cytoplasma of gastric epithelial cells and revealed its increased expression after H. pylori eradication. CONCLUSIONS: The data presented suggest that amphiregulin, heparin binding EGF and TGF-alpha are important EGF receptor ligands in the gastric mucosa. H. pylori infection apparently suppresses their mRNA as well as receptor expression that is reversed by H. pylori eradication. This deficiency of the gastroprotective EGF system may contribute to the gastric pathogenicity of H. pylori infection.     

Eradication therapy of Helicobacter pylori directly induces apoptosis in inflammation-related immunocytes in the gastric mucosa--possible mechanism for cure of peptic ulcer disease and MALT lymphoma with a low-grade malignancy

BACKGROUND/AIMS: A possibility that the eradication therapy not only eliminates Helicobacter pylori (H. pylori) but also influences some factors regulating pathological changes in the gastric mucosa should be taken into consideration from some phenomena. Such as non-recurrent cases of peptic ulcer long-term in spite of unsuccessful anti-H. pylori eradication therapy and the effectiveness of eradication therapy for mucosa-associated lymphoid tissue with a low-grade malignancy except stomach. We hypothesized and investigated that antibiotic treatment for elimination of H. pylori might directly affect inflammatory cells to induce apoptosis in them and protect against pathological changes of gastric mucosa. METHODOLOGY: Subjects consisted of twenty-one patients with chronic gastritis. All were H. pylori positive and we investigated the effects of eradication therapy of H. pylori on inflammation-related immunocytes in the gastric mucosa of patients with chronic gastritis caused by H. pylori isolated mononuclear leukocytes which were taken from the patients and were examined for apoptosis-related morphological changes and DNA fragmentation before and after the therapy. Eradication therapy of H. pylori was performed by lansoprazole 30 mg/day, amoxicillin 1500 mg/day and clarithromycin 400 mg/day for one week. RESULTS: After the H. pylori eradication therapy, regardless of its effect on H. pylori status, marked vacuolation and degeneration were observed in mononuclear leukocytes in the gastric mucosa with a concomitant enhancement of nuclear DNA fragmentation. CONCLUSIONS: This observation suggests that H. pylori eradication therapy itself induces apoptosis in mononuclear leukocytes in the gastric mucosa.     

胃癌患者检测表皮生长因子及受体的意义

目的:探讨表皮生长因子(EGF)及其受体(EGFR)的表达与胃癌发生及胃癌生物学行为的关系。方法:采用免疫组化S-P法对50例胃癌进行研究。结果:EGF和EGFR在早期胃癌中的阳性率均为20％(2/10),在进展期胃癌的阳性率分别为62.5％(25/40)和60％(24/40),进展期胃癌EGF和EGFR的阳性率均显著高于早期胃癌(P<0.05)。有转移组的EGF及EGFR阳性率高于无转移组(P<0.05)。EGF及EGFR的表达与胃癌的组织学类型有关。结论:EGF及EGFR阳性的肿瘤可能具有更强的浸润与转移能力,检测EGF和EGFR有助于判断胃癌预后。     

Eradication of Helicobacter pylori normalizes elevated mucosal levels of epidermal growth factor and its receptor

OBJECTIVE: Helicobacter pylori (H. pylori) infection has been linked to gastric cancer. The factors that promote carcinogenesis remain unknown. Epidermal growth factor (EGF) has been shown to be a potent epithelial mitogen and oncoprotein when sustained over expression occurs. Our aim was to compare gastric mucosal levels of EGF and its receptor (EGFR) among controls, H. pylori infected subjects, and subjects following H. pylori eradication using quantitative flow cytometric analysis. METHODS: Patients referred for evaluation of dyspepsia underwent EGD and six antral biopsies were performed (two each for rapid urease testing (RUT), histopathology, and flow cytometry). Controls were those found to be H. pylori negative while subjects had confirmed infection. The study patients were treated, then had repeat EGD with biopsies. RESULTS: There were 17 controls and 28 cases. Mean EGF and EGFR values were 2.69 and 2.46 for controls and 4.67 and 4.64 for subjects. Subjects' mean EGF was 73% higher (p = .035) and EGFR was 88% higher (p = 0.029) than controls. After treatment, the subjects' mean values declined 55% (p = 0.0001) for EGF and 40% (p = 0.002) for EGFR. Three subjects had persistent infection and showed no change in their EGF/EGFR levels. No difference was found among factor levels with respect to endoscopic findings. CONCLUSIONS: Both EGF and EGFR from gastric antral biopsies are increased nearly 2-fold in infection with H. pylori. Infection eradication reduces levels of both factors to those of controls. One major pathogenic mechanism for gastric mucosal hyperproliferation and possibly carcinogenesis related to H. pylori may be the over expression of EGF and increased receptor density of EGFR on gastric mucosal cells.     

表皮生长因子对SD大鼠萎缩性胃炎的作用

目的探讨表皮生长因子（EGF）对大鼠慢性萎缩性胃炎(CAG)胃黏膜病变的作用。方法将已经建立的SD大鼠CAG模型随机分成治疗组和对照组,治疗组给予EGF10μg/kg皮下注射,每日1次;对照组给予等容生理盐水皮下注射,每日1次,刺激12周后取出全胃,观察各组大鼠胃黏膜病理变化。结果治疗组大鼠胃黏膜炎性细胞浸润程度较对照组明显减轻（P<0.01）;两组大鼠胃黏膜腺体层厚度分别为(215.0±20.7)μm和(139.2±13.8)μm（P<0.01）,胃黏膜腺体层厚度/黏膜肌层厚度分别为2.70±0.34和1.27±0.27（P<0.01）,单位长度内胃黏膜腺体数目分别为26.20±1.27和19.90±1.78（P<0.01）;治疗组胃黏膜腺体增殖细胞核抗原(PCNA)表达阳性的宽度(77.70±4.16)μm较对照组(54.40±4.54)μm明显增加（P<0.01）。治疗组大鼠胃黏膜腺体排列规则,未发现有恶性增殖现象。结论EGF对SD大鼠CAG模型的胃黏膜萎缩有逆转治疗作用。EGF促进大鼠胃黏膜细胞PCNA阳性表达是其对大鼠CAG损伤的保护性增殖作用。     

长期饮酒合并幽门螺杆菌感染时胃黏膜损伤程度与EGF和PGE2的关系

目的探讨长期饮酒合并幽门螺杆菌感染时胃黏膜损伤的程度与胃液及血液中EGF及PGE2之间的关系。方法对2007年1月～2010年12月符合条件的长期饮酒合并幽门螺杆菌感染的56例患者进行内镜下胃黏膜活检组织的病理学观察,同时抽静脉血及胃液用ELISA法检测EGF及PGE2浓度。结果长期饮酒合并幽门螺杆菌感染胃黏膜中重度慢性炎症组患者血清和胃液EGF浓度明显高于轻度慢性炎症组患者血清和胃液EGF浓度(P=0.000;P=0.018);胃黏膜中重度萎缩组患者血清EGF浓度明显高于胃黏膜轻度萎缩组患者血清EGF浓度(P=0.000);胃黏膜中重度肠化组患者血清EGF浓度明显高于胃黏膜胃黏膜轻度肠化组患者血清EGF浓度(P=0.000),而胃黏膜中重度肠化组患者血清PGE2浓度明显降低(P=0.034);胃黏膜有不典型增生组患者血清和胃液中EGF浓度明显高于胃黏膜无不典型增生组患者血清和胃液中EGF浓度(P=0.000;P=0.044)。结论长期饮酒合并幽门螺杆菌感染引起血液中EGF升高与患者胃黏膜慢性炎症、萎缩和肠化加重及不典型增生的发生有关。而胃液中EGF浓度的升高仅与胃黏膜慢性炎症和不典型增生发生相关。在胃黏膜肠化患者中血清中PGE2明显降低。     

胃粘膜萎缩与Hp感染淋巴组织增生的关系

目的研究幽门螺杆菌（Ｈｐ）诱生的胃粘膜相关淋巴组织（ＭＡＬＴ）增生与萎缩关系及Ｈｐ根除后淋巴滤泡（ＬＦ）消失情况．方法光镜观察２５８例Ｈｐ阳性的慢性胃炎三联（奥美拉唑、克拉霉素、痢特灵，７ｄ）药治疗前后（１ｍｏ及１ａ）及正常胃粘膜２５例的ＬＦ检出率和聚集强度．结果慢性胃炎ＬＦ总检出率为７２５％；萎缩性胃炎＞浅表性胃炎，而正常胃粘膜ＬＦ检出率为４％；慢性胃炎ＬＦ聚集强度与粘膜炎症程度呈正相关（ｒ＝０６５，Ｐ＜００１）；但与粘膜萎缩程度呈负相关（ｒ＝－０６９，Ｐ＜００１）；治疗后慢性胃炎ＬＦ检出率和聚集强度明显减低（Ｐ＜００１）；腺上皮萎缩与ＬＦ形成关系密切．结论胃ＭＡＬＴ增生及相伴的免疫反应，可能是引起Ｈｐ相关性胃炎出现胃粘膜萎缩的重要原因之一．     

Ghrelin and Helicobacter pylori infection

Ghrelin is primarily secreted from the stomach and has been implicated in the coordination of eating behavior and weight regulation. Ghrelin also plays an essential role in the mechanism of gastric mucosal defense. Thus, it is important to clarify which diseases primar- ily influence changes in plasma ghrelin concentrations. Helicobacter pylori （H pylor/~ infection is involved in the pathogenesis of gastritis, gastric and duodenal ulcer, gastric carcinoma, and mucosa-associated lym- phoid tissue lymphoma. H pylori eradication is related to body weight change. Compared, H pylori infected and negative subjects with normal body mass index, plasma ghrelin concentration, gastric ghrelin mRNA, and the number of ghrelin producing cells in gastric mucosa are significantly lower in Hpylori infected sub- jects than in Hpylori-negative controls. Plasma ghrelin concentration decreases with the progression of gastric atrophy. Impaired gastric ghrelin production in associa- tion with atrophic gastritis induced by Hpylori infection accounts for the decrease in plasma ghrelin concentra- tion. However, the ratio of plasma acylated ghrelin to total ghrelin levels is higher in patients with chronic atrophic gastritis than in healthy subjects. This may re- sult from the＇ compensatory increase in plasma active ghrelin concentration in response to gastric atrophy. After H pylori eradication, gastric preproghrelin mRNA expression is increased nearly 4-fold in most cases. However, changes in plasma ghrelin concentrations be- fore and after Hpylori cure are not associated with the gastric ghrelin production. Plasma ghrelin changes are inversely correlated with both body weight change and initial plasma ghrelin levels.     

芪莲舒痞汤治疗慢性萎缩性胃炎癌前病变的临床研究

[目的]探讨以络病理论为指导的芪莲舒痞汤治疗慢性萎缩性胃炎（CAG）癌前病变（PLGC）的临床疗效。[方法]将88例符合标准的CAG伴PLGC患者随机分为芪莲舒痞汤治疗（治疗）组56例及胃复春治疗（对照）组32例,详细记录2组治疗前后临床症状及胃镜、病理、幽门螺杆菌（Hp）感染的情况。[结果]治疗组总有效率89.30%,对照组总有效率68.75%;治疗组疗效优于对照组（P〈0.05）。在患者症状积分、病理积分、Hp清除率方面,治疗组效果也优于对照组（P〈0.05或〈0.01）。[结论]芪莲舒痞汤治疗CAG PLGC疗效确切,且安全性良好,值得临床推广应用。