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幽门螺杆菌感染的人胃黏膜中肝素结合表皮生长因子样生长因子和双调蛋白表达上调。

Up-regulation of heparin binding epidermal growth factor-like growth factor and amphiregulin expression in Helicobacter pylori-infected human gastric mucosa.

作者信息

Tuccillo C, Manzo B A, Nardone G, D'Argenio G, Rocco A, Di Popolo A, Della Valle N, Staibano S, De Rosa G, Ricci V, Del Vecchio Blanco C, Zarrilli R, Romano M

机构信息

Department of Medicine, Gastroenterology, Second University of Naples, Italy.

出版信息

Dig Liver Dis. 2002 Jul;34(7):498-505. doi: 10.1016/s1590-8658(02)80108-6.

DOI:10.1016/s1590-8658(02)80108-6
PMID:12236483
Abstract

BACKGROUND

Host response plays a major role in pathogenesis of Helicobacter pylori-induced gastroduodenal disease including adenocarcinoma of distal stomach. Epidermal growth factor-related growth factors are important modulators of gastric homeostasis in normal and damaged gastrointestinal mucosa.

AIM

To evaluate expression of heparin binding epidermal growth factor and amphiregulin in antral mucosa of Helicobacter pylori-infected and non-infected dyspeptic patients and to correlate levels of heparin binding-epidermal growth factor and amphiregulin mRNA with mitogenic activity of gastric epithelial cells.

METHODS

A total of 10 Helicobacter pylori-infected and 15 Helicobacter pylori non-infected (10 with and 5 without gastritis) dyspeptic patients were studied. Diagnosis of Helicobacter pylori infection was based on rapid urease test and histology. Heparin binding-epidermal growth factor and amphiregulin mRNA expression in antral mucosa were assessed by reverse transcriptase-polymerase chain reaction. Protein expression and localization of both peptides were determined by immunohistochemistry. Mitogenic activity of antral gastric mucosa was assessed by determination of proliferating cell nuclear antigen labelling index by immunohistochemistry.

RESULTS

Heparin binding-epidermal growth factor and amphiregulin mRNA expression increased in Helicobacter pylori-infected vs Helicobacter pylori non-infected patients. Heparin binding-epidermal growth factor and amphiregulin immunostaining was more intense and deeper in gastric gland compartment in infected mucosa than in non-infected mucosa. Increase in heparin binding-epidermal growth factor and amphiregulin mRNA expression significantly correlated with increase in proliferating cell nuclear antigen labelling index.

CONCLUSIONS

Helicobacter pylori gastritis is associated with up-regulation of heparin binding-epidermal growth factor and amphiregulin which correlates with increased mitogenic activity of gastric mucosa. Increased heparin binding-epidermal growth factor and amphiregulin expression is postulated to contribute to reparative response of gastric mucosa to Helicobacter pylori infection.

摘要

背景

宿主反应在幽门螺杆菌诱导的胃十二指肠疾病(包括远端胃癌)的发病机制中起主要作用。表皮生长因子相关生长因子是正常和受损胃肠道黏膜中胃稳态的重要调节因子。

目的

评估幽门螺杆菌感染和未感染的消化不良患者胃窦黏膜中肝素结合表皮生长因子和双调蛋白的表达,并将肝素结合表皮生长因子和双调蛋白mRNA水平与胃上皮细胞的促有丝分裂活性相关联。

方法

共研究了10例幽门螺杆菌感染的消化不良患者和15例幽门螺杆菌未感染的消化不良患者(10例有胃炎,5例无胃炎)。幽门螺杆菌感染的诊断基于快速尿素酶试验和组织学检查。通过逆转录聚合酶链反应评估胃窦黏膜中肝素结合表皮生长因子和双调蛋白mRNA的表达。通过免疫组织化学确定两种肽的蛋白表达和定位。通过免疫组织化学测定增殖细胞核抗原标记指数来评估胃窦黏膜的促有丝分裂活性。

结果

与幽门螺杆菌未感染的患者相比,幽门螺杆菌感染患者中肝素结合表皮生长因子和双调蛋白mRNA表达增加。在感染的黏膜中,胃腺区的肝素结合表皮生长因子和双调蛋白免疫染色比未感染的黏膜更强烈、更深。肝素结合表皮生长因子和双调蛋白mRNA表达的增加与增殖细胞核抗原标记指数的增加显著相关。

结论

幽门螺杆菌胃炎与肝素结合表皮生长因子和双调蛋白的上调有关,这与胃黏膜促有丝分裂活性增加相关。推测肝素结合表皮生长因子和双调蛋白表达的增加有助于胃黏膜对幽门螺杆菌感染的修复反应。

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