Thomson A B R, Appleman S, Keelan M, Wallace J L
Nutrition and Metabolism Research Group, Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Canada.
Dig Dis Sci. 2003 Feb;48(2):308-14. doi: 10.1023/a:1021979510860.
Previous studies have shown that the bisphosphonates (BP) vary in their damaging effect on the gastric mucosa, and endoscopy scores (erosions or erosions plus ulcers) after 1 and 2 weeks use of BP were significantly lower in H. pylori-positive versus -negative subjects. The mechanism of this damaging effect of BP and the interaction with H. pylori is unknown. As part of a separately reported study of the incidence of gastric damage after 2 weeks of treatment of healthy female postmenopausal volunteers with risedronate (5 mg/day) or alendronate (10 mg/day), gastric aspirates were taken at the time of the baseline esophagogastroduodenoscopy (EGD), and again at 1 and 2 weeks after daily intake of a BP At the time of the third EGD, when the volunteers had been on risedronate or alendronate for 2 weeks, antral biopsies were taken from normal-appearing mucosa. Gastric juice and antral biopsies were assessed for their concentration of the cytokines interleukin-la (IL-1alpha), IL-8, IL-13, and epidermal growth factor (EGF). H. pylori, the use of BP, and development of gastric mucosal lesions had no effect on gastric mucosal concentrations of IL-1alpha, IL-13, or EGF. In contrast, the concentration of IL-8 in antral mucosal biopsies of volunteers given BP for 2 weeks was higher in the presence than in the absence of an H. pylori infection and was increased further in those who develop lesions associated with the use of BP. There was no correlation between gastric mucosal and gastric juice concentrations of IL-8. Gastric juice concentrations of IL-8 and EGF were not affected by H. pylori status, the use of BP, or the development of lesions. However, gastric juice concentrations of IL-1alpha were numerically lower in those who were negative for H. pylori with no mucosal lesions (Hp-L-), intermediate in those who were H. pylori-negative with lesions (Hp-L+), and highest in those who were positive for H. pylori and had lesions (Hp+L+). The gastric juice concentration of IL-13 was threefold higher in the absence than in the presence of H. pylori, and the relative abundance of IL-13 was: Hp-L- >Hp-L+ >Hp+L(-1) >Hp+L+. The prostaglandin E2 concentration in gastric antral biopsies was similar in the four groups and was unchanged with the in vitro biopsy incubation with celecoxib. We speculate that the higher gastric endoscopy scores observed with the use of BP in H. pylori negative as compared with H. pylori positive individuals is due to their lower mucosal concentration of IL-8 as well as the lower gastric juice concentration of IL-1alpha and higher concentration of IL-13.
先前的研究表明，双膦酸盐（BP）对胃黏膜的损伤作用各不相同，在幽门螺杆菌阳性和阴性受试者中，使用BP 1周和2周后的内镜评分（糜烂或糜烂加溃疡），幽门螺杆菌阳性者显著低于阴性者。BP这种损伤作用的机制以及与幽门螺杆菌的相互作用尚不清楚。作为一项单独报告的关于健康绝经后女性志愿者使用利塞膦酸钠（5毫克/天）或阿仑膦酸钠（10毫克/天）治疗2周后胃损伤发生率研究的一部分，在基线食管胃十二指肠镜检查（EGD）时采集胃抽吸物，在每日摄入BP 1周和2周后再次采集。在第三次EGD时，即志愿者使用利塞膦酸钠或阿仑膦酸钠2周时，从外观正常的黏膜取胃窦活检组织。评估胃液和胃窦活检组织中细胞因子白细胞介素-1α（IL-1α）、IL-8、IL-13和表皮生长因子（EGF）的浓度。幽门螺杆菌、BP的使用以及胃黏膜病变的发生对胃黏膜中IL-1α、IL-13或EGF的浓度没有影响。相比之下，使用BP 2周的志愿者胃窦黏膜活检组织中，存在幽门螺杆菌感染时IL-8的浓度高于无感染时，且在出现与使用BP相关病变的志愿者中进一步升高。胃黏膜和胃液中IL-8的浓度之间没有相关性。胃液中IL-8和EGF的浓度不受幽门螺杆菌状态、BP的使用或病变发生的影响。然而，幽门螺杆菌阴性且无黏膜病变者（Hp-L-）胃液中IL-1α的浓度在数值上较低，幽门螺杆菌阴性且有病变者（Hp-L+）居中，幽门螺杆菌阳性且有病变者（Hp+L+）最高。无幽门螺杆菌时胃液中IL-13的浓度比有幽门螺杆菌时高两倍，且IL-13的相对丰度为：Hp-L-＞Hp-L+＞Hp+L（-1）＞Hp+L+。四组胃窦活检组织中前列腺素E2的浓度相似，且在体外活检组织与塞来昔布孵育后无变化。我们推测，与幽门螺杆菌阳性个体相比，幽门螺杆菌阴性个体使用BP时观察到的更高胃内镜评分是由于其黏膜中IL-8浓度较低以及胃液中IL-1α浓度较低和IL-13浓度较高。
