High Dietary Salt Intake Exacerbates Helicobacter pylori-Induced Gastric Carcinogenesis
High Dietary Salt Intake Exacerbates Helicobacter pylori-Induced Gastric Carcinogenesis
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DOI：
10.1128/iai.01271-12
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发表时间：
2013-06-01
影响因子：
3.1
通讯作者：
Cover, Timothy L.
中科院分区：
文献类型：
--
作者：
Gaddy, Jennifer A.;Radin, Jana N.;Cover, Timothy L.
幽门螺杆菌在人胃中的持续定植是胃腺癌的危险因素，而幽门螺杆菌诱导的癌变依赖于一种名为CagA的细菌癌蛋白的作用。流行病学研究表明，高食盐摄入量也是胃癌的危险因素。为了研究高盐饮食的影响，我们用野生型(WT)cagA(+)幽门螺杆菌菌株或等基因cagA突变菌株感染蒙古沙土鼠，并以常规饲料或高盐饲料喂养动物。在感染4个月后，100%的WT感染/高盐饮食的动物，58%的WT感染/常规饮食的动物，没有cagA突变株感染的动物检测到胃腺癌(P<；0.0001)。在感染WT菌株的动物中，与正常饮食组相比，高盐饮食组的胃炎症更严重，胃pH值更高，壁细胞丢失增加，胃组织中白细胞介素1β(IL-1β)的表达增加，而海普西丁和氢钾ATPase(H，K-ATPase)的胃组织表达减少。以前的研究已经检测到CagA合成随着细菌培养液中盐浓度的增加而上调，并且，与体外结果一致，我们在体内检测到，与常规饮食相比，高盐饮食的动物体内cagA转录增加。感染了cagA突变株的动物胃部炎症水平较低，也没有出现低盐酸血症。这些结果表明，高盐饮食增强了cagA(+)幽门螺杆菌菌株的致癌作用。
Persistent colonization of the human stomach with Helicobacter pylori is a risk factor for gastric adenocarcinoma, and H. pylori-induced carcinogenesis is dependent on the actions of a bacterial oncoprotein known as CagA. Epidemiological studies have shown that high dietary salt intake is also a risk factor for gastric cancer. To investigate the effects of a high-salt diet, we infected Mongolian gerbils with a wild-type (WT) cagA(+) H. pylori strain or an isogenic cagA mutant strain and maintained the animals on a regular diet or a high-salt diet. At 4 months postinfection, gastric adenocarcinoma was detected in 100% of the WT-infected/high-salt-diet animals, 58% of WT-infected/regular-diet animals, and none of the animals infected with the cagA mutant strain (P < 0.0001). Among animals infected with the WT strain, those fed a high-salt diet had more severe gastric inflammation, higher gastric pH, increased parietal cell loss, increased gastric expression of interleukin 1 beta (IL-1 beta), and decreased gastric expression of hepcidin and hydrogen potassium ATPase (H,K-ATPase) compared to those on a regular diet. Previous studies have detected upregulation of CagA synthesis in response to increased salt concentrations in the bacterial culture medium, and, concordant with the in vitro results, we detected increased cagA transcription in vivo in animals fed a high-salt diet compared to those on a regular diet. Animals infected with the cagA mutant strain had low levels of gastric inflammation and did not develop hypochlorhydria. These results indicate that a high-salt diet potentiates the carcinogenic effects of cagA(+) H. pylori strains.