Tuo Biguang, Song Penghong, Wen Guorong, Sewald Xaver, Gebert-Vogl Bettina, Haas Rainer, Manns Michael, Seidler Ursula
Department of Gastroenterology, Affiliated Hospital of Zunyi Medical College, Zunyi, China.
J Infect Dis. 2009 Feb 15;199(4):505-12. doi: 10.1086/596318.
The pathogenic mechanisms involved in Helicobacter pylori-induced duodenal mucosal injury are incompletely understood. In the present study, we sought to investigate the effect of H. pylori vacuolating cytotoxin (VacA) on duodenal mucosal bicarbonate (HCO3-) secretion.
Concentrated bacterial culture supernatants from an H. pylori wild-type strain producing VacA with s1/m1 genotypes (P12) and from an isogenic mutant lacking VacA (P12DeltavacA) were used. HCO3- secretion by murine duodenal mucosa was examined in vitro in Ussing chambers. Duodenal mucosal histamine release was measured using enzyme-linked immunosorbent assay. The expression of histamine H2 receptor was examined by immunohistochemical analysis.
In a dose-dependent manner, the VacA-positive supernatant P12 reduced prostaglandin E2 (PGE2)-stimulated duodenal mucosal HCO3- secretion to a maximum of 49% (P<.0001), whereas P12DeltavacA did not result in significant inhibition (P>.05). Purified VacA had a similar effect. Histamine H2 receptor antagonists attenuated the effect of P12 on PGE2-induced HCO3- secretion. P12 stimulated duodenal histamine release in a dose-dependent manner, and exogenous histamine inhibited PGE2-stimulated duodenal HCO3- secretion. H2 receptor expression was found in duodenal epithelial cells, the enteric nerve plexus, and lymphocytes in Peyer's patch.
H. pylori VacA inhibits PGE2-stimulated duodenal epithelial HCO3- secretion by a histamine-dependent mechanism. This effect likely contributes to the damaging effect of H. pylori in the duodenal mucosa.
幽门螺杆菌诱导十二指肠黏膜损伤的致病机制尚未完全明确。在本研究中，我们旨在探讨幽门螺杆菌空泡毒素（VacA）对十二指肠黏膜碳酸氢盐（HCO3-）分泌的影响。
使用来自产生具有s1/m1基因型VacA的幽门螺杆菌野生型菌株（P12）和缺乏VacA的同基因突变体（P12DeltavacA）的浓缩细菌培养上清液。在Ussing室中体外检测小鼠十二指肠黏膜的HCO3-分泌。使用酶联免疫吸附测定法测量十二指肠黏膜组胺释放。通过免疫组织化学分析检测组胺H2受体的表达。
VacA阳性上清液P12以剂量依赖性方式将前列腺素E2（PGE2）刺激的十二指肠黏膜HCO3-分泌最多降低49%（P<.0001），而P12DeltavacA未导致显著抑制（P>.05）。纯化的VacA具有类似作用。组胺H2受体拮抗剂减弱了P12对PGE2诱导的HCO3-分泌的作用。P12以剂量依赖性方式刺激十二指肠组胺释放，外源性组胺抑制PGE2刺激的十二指肠HCO3-分泌。在十二指肠上皮细胞、肠神经丛和派伊尔结中的淋巴细胞中发现了H2受体表达。
幽门螺杆菌VacA通过组胺依赖性机制抑制PGE2刺激的十二指肠上皮HCO3-分泌。这种作用可能导致幽门螺杆菌对十二指肠黏膜的损伤作用。
