Jaworski T, Sarosiek I, Sostarich S, Roeser K, Connor M, Brotze S, Wallner G, Sarosiek J
Kansas University Medical Center, Division of Gastroenterology and Hepatology, Center for Muscle and Nerve Function, Gastroenterology Research Laboratory, Kansas City, Kansas 66160-7350, USA.
Dig Dis Sci. 2005 Feb;50(2):357-65. doi: 10.1007/s10620-005-1611-3.
Rabeprazole augments gastric mucus and mucin production in humans. However, its potential restorative impact on gastric mucus and mucin production impairment, resulting from administration of naproxen, remained to be explored. Therefore, we measured the content of mucus and mucin in gastric juice (GJ) before and after administration of naproxen with rabeprazole or placebo. The study was approved by HSC at KUMC and conducted in 21 asymptomatic, H. pylori-negative volunteers in a double-blind, placebo-controlled, crossover design. The content of gastric mucus in GJ, after exhaustive dialysis and complete lyophilization, was assessed gravimetrically, whereas the content of mucin was measured after its purification with equilibrium density-gradient ultracentrifugation in CsC1. Gastric mucus secretion during administration of naproxen with placebo declined significantly both in basal (by 44%; P < 0.001) and in pentagastrin-stimulated (by 35%; P < 0.001) conditions. Coadministration of rabeprazole significantly restored the naproxen-induced impairment in mucus production in basal conditions (by 47%; P < 0.01) and by 22% during stimulation with pentagastrin. Gastric mucin secretion during naproxen/placebo administration also declined significantly in both basal (by 39%; P < 0.01) and stimulated (by 49%; P = 0.003) conditions. Rabeprazole also significantly restored the naproxen-induced decline of gastric mucin output during pentagastrin-stimulated conditions (by 67%; P = 0.003) and by 40% in basal conditions (P = 0.05). The restorative capacity of rabeprazole on the quantitative impairment of gastric mucus and mucin during administration of naproxen may translate into a clinical benefit of protection of the upper alimentary tract from NSAID-related mucosal injury.
雷贝拉唑可增加人体胃黏液和黏蛋白的分泌。然而,萘普生给药导致胃黏液和黏蛋白分泌受损,雷贝拉唑对其潜在的修复作用仍有待探索。因此,我们测量了服用萘普生加雷贝拉唑或安慰剂前后胃液(GJ)中黏液和黏蛋白的含量。该研究经堪萨斯大学医学中心(KUMC)机构审查委员会(HSC)批准,以双盲、安慰剂对照、交叉设计在21名无症状、幽门螺杆菌阴性的志愿者中进行。经过彻底透析和完全冻干后,通过重量法评估GJ中胃黏液的含量,而黏蛋白的含量则在通过氯化铯平衡密度梯度超速离心法纯化后进行测量。服用萘普生加安慰剂期间,基础状态下(下降44%;P<0.001)和五肽胃泌素刺激状态下(下降35%;P<0.001)胃黏液分泌均显著下降。雷贝拉唑联合给药显著恢复了萘普生在基础状态下引起的黏液分泌损伤(恢复47%;P<0.01),在五肽胃泌素刺激时恢复22%。服用萘普生/安慰剂期间,基础状态下(下降39%;P<0.01)和刺激状态下(下降49%;P=0.003)胃黏蛋白分泌也显著下降。雷贝拉唑还显著恢复了五肽胃泌素刺激状态下萘普生引起的胃黏蛋白分泌下降(恢复67%;P=0.003),在基础状态下恢复40%(P=0.05)。雷贝拉唑对萘普生给药期间胃黏液和黏蛋白定量损伤的修复能力可能转化为临床上保护上消化道免受非甾体抗炎药相关黏膜损伤的益处。