海洋深層水對感染胃幽門螺旋桿菌之BALB/c小鼠和AGS細胞可能的預防與治療效用

Abstract

幽門螺旋桿菌透過感染胃黏膜來引起長期胃發炎，過去已證實其感染與胃潰瘍、十二指腸潰瘍、胃癌等疾病發生有關。海洋深層水富含微量營養素（Micronutrients）與鈣、鎂等礦物質（Minerals），且具有極少病原菌與乾淨等特性。本篇研究探討台灣東部抽取之濃縮海洋深層水之抑菌能力，並使用人類胃癌細胞株（AGS cell）和BALB/c品系小鼠進行感染實驗，來探討給予海洋深層水是否對感染幽門螺旋桿菌具有預防與治療效用。此外，我們利用質譜儀以及真空冷凍乾燥技術來分析海洋深層水內含之未知物，並進一步探討其抑菌能力。 研究結果顯示不同處理之海洋深層水皆有抑菌效果，抑菌效果逹50%之海洋深層水硬度為1200－3600 ppm，而抑菌效果逹90%之海洋深層水硬度為2400－3600 ppm。因此本篇選用硬度1200 ppm與2400 ppm之海洋深層水進行實驗，從免疫化學結果得知感染後經過海洋深層水處理之細胞相對感染組其細胞凋亡、發炎性細胞凋亡都明顯下降，細胞自噬作用則有增加之趨勢。而經過海洋深層水預防及治療之受感染小鼠相對感染組其細胞凋亡、發炎性細胞凋亡以及氧化壓力均明顯下降，細胞自噬作用則上升。另外，從質譜圖可以得知海洋深層水除了鈣、鎂等礦物質外，還含有大分子之有機物，且其去除二價離子後仍有抑菌的效果，我們推論海洋深層水的未知有機物具有抑菌之效用。 綜合以上結果得知，台灣東部抽取之濃縮海洋深層水確實有抑菌之效果，並且對感染幽門螺旋桿菌有預防與治療效用，而達到保護胃黏膜，而海洋深層水之有效抑菌成份未來會進一步探討。希望未來能使用海洋深層水作為天然藥物以取代抗生素療法來預防及治療幽門螺旋桿菌。Helicobacter pylori (H. Pylori) infects the gastric mucosa and causes long-term inflammation. Previous studies have demonstrated H. pylori may cause gastric ulcer, duodenal ulcer and gastric cancer. Deep sea water (DSW) is rich in micronutrients, minerals such as calcium and magnesium ions and high purity, but less in pathogen. This study investigated the antibacterial activity of different types of refined DSW, gathered from eastern Taiwan, and the prevention and therapeutic effect of DSW on H. pylori-infected-AGS cells and H. pylori-infected-BALB/c mice. We further used a mass spectrometer and freeze-drying to analyze the effective antimicrobial composition of DSW. The results showed that different types of refined DSW all had antibacterial effects, to reach 50% of antibacterial effects, the hardness of DSW was between 1200-3600 ppm, while achieving 90% of antibacterial effects, the hardness went up to 2400-3600 ppm. Therefore, we used DSW1200 (hardness: 1200 ppm) and DSW2400 (hardness: 2400 ppm) for both cells and animal treatments. The immunochemical tests indicated that DSW-treated H. pylori-infected AGS cells, DSW-pretreated H. pylori-infected mice and DSW-treated H. pylori-infected mice all significantly decreased the expression of apoptosis, pyroptosis and oxidative stress, but increased autophagy expression. Furthermore, it was found that DSW contained massive organic matters by using a mass spectrometer. Another result showed that EDTA in DSW to chelate divalent metal ions still had antibacterial effects. Based on these data, we suggested the antibacterial effective compounds in DSW may be an unknown organic matter, not calcium or magnesium. Based on the above results, the refined DSW extracted from eastern Taiwan has the ability of preventive, therapeutic and protective effects on H. pylori infection. The evidence revealed the antibacterial effects of DSW are derived from unknown compounds, but not associated with calcium and magnesium ions. We wish to use DSW as a natural medical alternative of antibiotics to prevent and cure H. pylori infection.