Martinsen Tom C, Benestad Sylvie L, Moldal Torfinn, Waldum Helge L
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Scand J Gastroenterol. 2011 Dec;46(12):1418-22. doi: 10.3109/00365521.2011.619277. Epub 2011 Sep 22.
Gastric juice is a unique combination of hydrochloric acid and the proteolytic enzyme pepsin. Its main function is to inactivate ingested microorganisms. Prions cause fatal transmissible degenerative encephalopathies in animals and man. These diseases have attracted attention due to the proposed link between bovine spongiform encephalopathy in cattle and the occurrence of a new variant Creutzfeldt-Jakob disease in humans where the most probable route of transmission is via contaminated food. The role of gastric juice in the protection against these agents is not settled.
The aim of this study was to examine if drug-induced gastric hypoacidity increases the susceptibility of prion infection transmitted by the oral route.
Forty-six mice (tg338) were given brain homogenates contaminated with scrapie by gastric intubation. Twenty-two of these animals were concomitantly dosed with omeprazole increasing the median gastric pH from 1.2 to 5.3. After 381 days, the animals were sacrificed and all the brains were examined for detection of pathogenic prion proteins by enzyme-linked immunosorbent assay and western blot.
Drug-induced decrease in gastric acidity more than doubled the rate (59% vs. 25%, p < 0.035) of brain infection compared to controls with normal gastric acidity at the time of inoculation.
Our results demonstrate that the normal gastric juice constitutes a significant defense against prion disease in mice. Thus, gastric hypochlorhydria would be expected to enhance the susceptibility to prion infection by the oral route. This finding may have relevance to the pathogenesis of the new variant Creutzfeldt-Jakob disease and prion diseases in general.
胃液是盐酸和蛋白水解酶胃蛋白酶的独特组合。其主要功能是使摄入的微生物失活。朊病毒可导致动物和人类致命的传染性退行性脑病。由于牛海绵状脑病与人类新型克雅氏病的发生之间存在推测的联系，这些疾病引起了关注，其中最可能的传播途径是通过受污染的食物。胃液在抵御这些病原体方面的作用尚未确定。
本研究的目的是检查药物诱导的胃低酸度是否会增加经口传播的朊病毒感染的易感性。
46只（tg338）小鼠经胃插管给予感染羊瘙痒病的脑匀浆。其中22只动物同时给予奥美拉唑，使胃pH值中位数从1.2提高到5.3。381天后，处死动物，所有脑均通过酶联免疫吸附测定和蛋白质印迹法检测致病性朊病毒蛋白。
与接种时胃酸正常的对照组相比，药物诱导的胃酸降低使脑感染率增加了一倍多（59%对25%，p<0.035）。
我们的结果表明，正常胃液对小鼠朊病毒病构成了重要防御。因此，胃低酸预计会增加经口途径感染朊病毒的易感性。这一发现可能与新型克雅氏病及一般朊病毒病的发病机制有关。
