Choi Yoon Jeong, Kim Nayoung, Lee Ju Yup, Nam Ryoung Hee, Suh Ji Hyung, Lee Sun Min, Ham Min Hee, Jo Hyun Jin, Shim Young Kwang, Park Yo Han, Lee Jong-Chan, Choi Yoon Jin, Lee Hye Seung, Lee Dong Ho
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Gut Liver. 2016 Sep 15;10(5):749-56. doi: 10.5009/gnl15584.
BACKGROUND/AIMS: The aim of this study was to evaluate the effect of the synthetic S-allyl-L-cysteine (SAC) PMK-S005 on gastric acid secretion, inflammation, and antioxidant enzymes in aging rats.
The rats were divided into four groups at 31 weeks of age and were continuously fed a diet containing a vehicle control, PMK-S005 (5 or 10 mg/kg), or lansoprazole (5 mg/kg). Gastric acid secretion and connective tissue thickness of the lamina propria were evaluated at 74 weeks and 2 years of age. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and COX-2 levels were measured by using enzyme-linked immunosorbent assays (ELISAs) or Western blot assays. Levels of antioxidant enzymes, including heme oxyganase 1 (HO-1) and
NAD(P)H: quinone oxidoreductase 1 (NQO-1), were also measured.
As the rats aged, gastric acid secretion significantly decreased, and the connective tissue of the lamina propria increased. However, 74-week-old rats in the PMK-S005 group exhibited greater levels of gastric acid secretion than those of the control and lansoprazole groups. The increase of TNF-α, IL-1β, and COX- 2 expression in 74-week and 2-year-old control rats were inhibited by PMK-S005. In addition, the decrease in HO-1 and NQO-1 protein expression that occurred with aging was inhibited by PMK-S005 in the 74-week-old rats.
These results suggest that PMK-S005 has therapeutic potential as an antiaging agent to ameliorate age-related gastric acid secretion, inflammation, and oxidative stress in the stomach.
背景/目的:本研究旨在评估合成的S-烯丙基-L-半胱氨酸(SAC)PMK-S005对衰老大鼠胃酸分泌、炎症和抗氧化酶的影响。
大鼠在31周龄时分为四组,持续喂食含载体对照、PMK-S005(5或10毫克/千克)或兰索拉唑(5毫克/千克)的饮食。在74周龄和2岁时评估胃酸分泌和固有层结缔组织厚度。使用酶联免疫吸附测定(ELISA)或蛋白质印迹法检测肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和COX-2水平。还测量了抗氧化酶水平,包括血红素加氧酶1(HO-1)和NAD(P)H:醌氧化还原酶1(NQO-1)。
随着大鼠年龄增长,胃酸分泌显著减少,固有层结缔组织增加。然而,PMK-S005组74周龄大鼠的胃酸分泌水平高于对照组和兰索拉唑组。PMK-S005抑制了74周龄和2岁对照大鼠中TNF-α、IL-1β和COX-2表达的增加。此外,PMK-S005抑制了74周龄大鼠中随着衰老而发生的HO-1和NQO-1蛋白表达的下降。
这些结果表明,PMK-S005作为一种抗衰老剂具有治疗潜力,可改善与年龄相关的胃酸分泌、炎症和胃中的氧化应激。