Goswami Sumanta Kumar, Rand Amelia Ann, Wan Debin, Yang Jun, Inceoglu Bora, Thomas Melany, Morisseau Christophe, Yang Guang-Yu, Hammock Bruce D
Department of Entomology and Nematology, and Comprehensive Cancer Center, University of California, Davis, CA 95616, USA.
Department of Pathology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA.
Life Sci. 2017 Jul 1;180:114-122. doi: 10.1016/j.lfs.2017.05.018. Epub 2017 May 15.
This research was conducted to evaluate the hypothesis that gastric ulcers caused by the NSAID diclofenac sodium (DCF) can be prevented by the soluble epoxide hydrolase inhibitor TPPU.
Mice were administered a single dose of 10, 30 or 100mg/kg of DCF. Once an ulcerative dose of DCF was chosen, mice were pretreated with TPPU for 7days at 0.1mg/kg to evaluate anti-ulcer effects of the sEH inhibitor on anatomy, histopathology, pH, inflammatory markers and epithelial apoptosis of stomachs.
Diclofenac caused ulceration of the stomach at a dose of 100mg/kg and a time post dose of 6h. Ulcers generated under these conditions were associated with a significant increase in the levels of TNF-α and IL-6 in serum and increased apoptosis compared to control mice. Pretreatment with TPPU resulted in a decrease of ulceration in mice treated with DCF with a significant decrease in the level of apoptosis, TNF-α and IL-6 in the serum in comparison to diclofenac-treated mice. TPPU did not affect the pH of the stomach, whereas omeprazole elevated the pH of the stomach as expected. A similar anti-ulcer effect was observed in sEH gene knockout mice treated with DCF.
The sEH inhibitor TPPU decreases the NSAID-induced stomach ulcers.
本研究旨在评估可溶性环氧化物水解酶抑制剂TPPU能否预防非甾体抗炎药双氯芬酸钠（DCF）所致胃溃疡这一假说。
给小鼠单次给予10、30或100mg/kg的DCF。选定DCF的致溃疡剂量后，用0.1mg/kg的TPPU对小鼠进行7天预处理，以评估sEH抑制剂对胃的解剖结构、组织病理学、pH值、炎症标志物和上皮细胞凋亡的抗溃疡作用。
双氯芬酸钠在剂量为100mg/kg且给药后6小时可导致胃溃疡。与对照小鼠相比，在这些条件下产生的溃疡与血清中TNF-α和IL-6水平显著升高以及细胞凋亡增加有关。用TPPU预处理可使DCF处理的小鼠溃疡减少，与双氯芬酸钠处理的小鼠相比，血清中细胞凋亡水平、TNF-α和IL-6显著降低。TPPU不影响胃的pH值，而奥美拉唑如预期那样升高了胃的pH值。在用DCF处理的sEH基因敲除小鼠中也观察到了类似的抗溃疡作用。
sEH抑制剂TPPU可减少非甾体抗炎药引起的胃溃疡。
