Dexmedetomidine inhibits endoplasmic reticulum stress to suppress pyroptosis of hypoxia/reoxygenation-induced intestinal epithelial cells via activating the SIRT1 expression.

Abstract

Dexmedetomidine (Dex) can protect the intestine against ischemia/reperfusion (I/R)-induced injury. Sirtuin 1 (SIRT1) pathway, which could be activated by Dex, was reported to inhibit I/R injury. Pyroptosis plays an important role in intestinal diseases. We aimed to investigate whether Dex could attenuate pyroptosis of hypoxia/reoxygenation (H/R)-induced intestinal epithelial cells via activating SIRT1. The intestinal epithelial cell line IEC-6 with or without SIRT1 knockdown after H/R treatment was exposed to Dex, then cell viability, endoplasmic reticulum stress (ERS), apoptosis, pyroptosis, inflammatory cytokines production and SIRT1 expression were detected. Results showed that Dex treatment had no significant effect on IEC-6 cell viability but rescued the H/R-reduced cell viability. The expression of proteins involved in ERS including Grp78, Gadd153 and caspase 12 was enhanced upon H/R stimulation, but was reversely reduced by Dex. The cell apoptosis increased by H/R was also decreased by Dex. Additionally, Dex inhibited pyroptosis and inflammation, which were markedly promoted upon H/R stimulation. The expression of SIRT1, which was reduced after H/R treatment was also partially rescued by Dex. Finally, the above effects of Dex were all blocked by SIRT1 knockdown. In conclusion, Dex could inhibit H/R-induced intestinal epithelial cells ERS, apoptosis and pyroptosis via activating SIRT1 expression.