Lin Lee-Shuan, Kayasuga-Kariya Yuko, Nakamura Shugo, Shimohata Nobuyuki, Sakai Takamasa, Fujisawa Ayano, Akagi Yuki, Suzuki Shigeki, Chung Ung-Il, Sasaki Nobuo, Mochizuki Manabu
Department of Veterinary Medicine, National Pingtung University of Science and Technology, Neipu, Taiwan.
Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Dig Dis Sci. 2016 Aug;61(8):2242-2251. doi: 10.1007/s10620-016-4209-z. Epub 2016 May 31.
Aspirin is one of the most popular NSAIDs worldwide because of its anti-inflammatory and anticoagulant effects, and however, gastrointestinal injury remains a major complication. We previously reported co-lyophilized aspirin/trehalose (Lyo A/T) decreased the aspirin-induced gastric lesions in dogs.
This study investigated the mechanism of gastroprotective effects of trehalose in vitro and in vivo.
The apoptotic assays were performed in a human gastric carcinoma cell line, which was treated with aspirin, mixed aspirin/trehalose (Mix A/T) or Lyo A/T. Gastric ulcer severity was examined after oral administration of drugs in rats. In addition, the mucosal tissue apoptotic status in drug-treated rats was evaluated. Molecular dynamics simulations and laser Raman spectroscopy were performed in order to examine the molecular properties of Lyo A/T.
DNA fragmentation was detected in AGS cells that were treated with aspirin and Mix A/T, but not in the Lyo A/T-treated cells. There were fewer apoptotic cells in the Lyo A/T-treated cells than in the other cells. Gastric injury was reduced in rats that received oral Lyo A/T compared with the others, while PGE2 synthesis was equally decreased in all groups. TUNEL assay and immunohistochemistry of cleaved caspase-3 in the mucosal tissues also revealed that Lyo A/T treatment induced less apoptosis than the others. The Lyo A/T spectrum showed clear differences in several Raman bands compared with that of Mix A/T.
Our data showed that co-lyophilization of aspirin with trehalose reduced gastric injury, potentially through suppression of aspirin-induced mucosal cell apoptosis while retaining its anti-inflammatory effects.
阿司匹林因其抗炎和抗凝作用，是全球最常用的非甾体抗炎药之一，然而，胃肠道损伤仍然是一个主要并发症。我们之前报道过共冻干的阿司匹林/海藻糖（Lyo A/T）可减少犬类阿司匹林诱导的胃损伤。
本研究调查了海藻糖在体外和体内胃保护作用的机制。
在人胃癌细胞系中进行凋亡检测，该细胞系用阿司匹林、混合阿司匹林/海藻糖（Mix A/T）或Lyo A/T处理。在大鼠口服给药后检查胃溃疡严重程度。此外，评估药物处理大鼠的黏膜组织凋亡状态。进行分子动力学模拟和激光拉曼光谱分析以检查Lyo A/T 的分子特性。
在用阿司匹林和Mix A/T处理的AGS细胞中检测到DNA片段化，但在Lyo A/T处理的细胞中未检测到。Lyo A/T处理的细胞中凋亡细胞比其他细胞少。与其他组相比，口服Lyo A/T的大鼠胃损伤减轻，而所有组中PGE2合成均同等程度降低。黏膜组织中TUNEL检测和裂解的caspase-3免疫组化也显示，Lyo A/T处理诱导的凋亡比其他处理少。与Mix A/T相比，Lyo A/T光谱在几个拉曼谱带中显示出明显差异。
我们的数据表明，阿司匹林与海藻糖共冻干可减轻胃损伤，可能是通过抑制阿司匹林诱导的黏膜细胞凋亡，同时保留其抗炎作用。
