Mita Masaharu, Satoh Masahiko, Shimada Akinori, Okajima Mina, Azuma Sadahiro, Suzuki Junko S, Sakabe Kou, Hara Shuntaro, Himeno Seiichiro
Laboratory Animal Research Center, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Am J Physiol Gastrointest Liver Physiol. 2008 Apr;294(4):G877-84. doi: 10.1152/ajpgi.00251.2007. Epub 2008 Jan 31.
Infection with the gastric pathogen Helicobacter pylori (H. pylori) causes chronic gastritis, peptic ulcer, and gastric adenocarcinoma. These diseases are associated with production of reactive oxygen species (ROS) from infiltrated macrophages and neutrophiles in inflammatory sites. Metallothionein (MT) is a low-molecular-weight, cysteine-rich protein that can act not only as a metal-binding protein, but also as a ROS scavenger. In the present study, we examined the role of MT in the protection against H. pylori-induced gastric injury using MT-null mice. Female MT-null and wild-type mice were challenged with H. pylori SS1 strain, and then histological changes were evaluated with the updated Sydney grading system at 17 and 21 wk after challenge. Although the colonization efficiency of H. pylori was essentially the same for MT-null and wild-type mice, the scores of activity of inflammatory cells were significantly higher in MT-null mice than in wild-type mice at 17 wk after challenge. Histopathological examination revealed erosive lesions accompanied by infiltration of inflammatory cells in the infected MT-null mice but not in wild-type mice. Furthermore, activation of NF-kappaB and expression of NF-kappaB-mediated chemokines such as macrophage inflammatory protein-1alpha and monocytes chemoattractant protein-1 in gastric cells were markedly higher in MT-null mice than in wild-type mice. These results suggest that MT in the gastric mucosa might play an important role in the protection against H. pylori-induced gastric ulceration.
胃部病原体幽门螺杆菌（H. pylori）感染会引发慢性胃炎、消化性溃疡和胃腺癌。这些疾病与炎症部位浸润的巨噬细胞和中性粒细胞产生活性氧（ROS）有关。金属硫蛋白（MT）是一种低分子量、富含半胱氨酸的蛋白质，它不仅可以作为金属结合蛋白，还能作为ROS清除剂。在本研究中，我们使用MT基因敲除小鼠研究了MT在抵御幽门螺杆菌诱导的胃损伤中的作用。雌性MT基因敲除小鼠和野生型小鼠用幽门螺杆菌SS1菌株进行攻击，然后在攻击后17周和21周用更新的悉尼分级系统评估组织学变化。尽管幽门螺杆菌在MT基因敲除小鼠和野生型小鼠中的定植效率基本相同，但在攻击后17周，MT基因敲除小鼠中炎症细胞活性评分显著高于野生型小鼠。组织病理学检查显示，受感染的MT基因敲除小鼠出现糜烂性病变并伴有炎症细胞浸润，而野生型小鼠则未出现。此外，MT基因敲除小鼠胃细胞中NF-κB的激活以及NF-κB介导的趋化因子如巨噬细胞炎性蛋白-1α和单核细胞趋化蛋白-1的表达明显高于野生型小鼠。这些结果表明，胃黏膜中的MT可能在抵御幽门螺杆菌诱导的胃溃疡中发挥重要作用。
