TUDCA attenuates intestinal injury and inhibits endoplasmic reticulum stress-mediated intestinal cell apoptosis in necrotizing enterocolitis

摘要

Neonatal necrotizing enterocolitis (NEC) is a life-threatening disease with severe inflammation and intestinal cell apoptosis. Tauroursodeoxycholic acid (TUDCA) is a recognized endoplasmic reticulum stress (ERS) inhibitor which can inhibit cell apoptosis. Recently, intestinal cell apoptosis has been demonstrated to be vital for the pathogenesis of NEC. The purpose of the present study was to investigate the potential of TUDCA in the treatment of NEC and the possible mechanisms in vivo and in vitro. Our results showed that TUDCA reduced mortality rates, prolonged survival times, significantly diminished intestinal damage, and inhibited intestinal inflammation in the mouse model of NEC. The protective effect of TUDCA on the NEC mouse model was realized through inhibiting the expression levels of ERS markers and inhibiting the apoptosis of intestinal cells. In addition, TUDCA increased the expression of phospho-Akt (p-Akt). Furthermore, we confirmed that TUDCA inhibited the apoptosis of intestinal cells by modulating the PERK-eIF2 alpha ERS pathway and the Akt pathway in vitro studies. Besides, TUDCA effects were impaired by AKT specific inhibitor MK2206 in vitro studies. Therefore, these results indicated that TUDCA alleviated intestinal injury in a mouse model of NEC and inhibited ERS-mediated intestinal cell apoptosis by activating the Akt pathway.