Dexmedetomidine prevents PDIA3 decrease by activating α2-adrenergic receptor to alleviate intestinal ischemia/reperfusion in mice

Abstract

Background: Dexmedetomidine (DEX) attenuates intestinal I/R injury, but its mechanism of action remains to be further elucidated. Protein disulfide isomerase A3 (PDIA3) has been reported as a therapeutic protein for the prevention and treatment of intestinal I/R injury. This study was to investigate whether PDIA3 is involved in intestinal protection of DEX and explore the underlying mechanisms. Methods: The potential involvement of PDIA3 in DEX attenuation of intestinal I/R injury was tested in PDIA3 Flox/Flox mice and PDIA3 conditional knockout (cKO) in intestinal epithelium mice subjected to 45 min of superior mesenteric artery occlusion followed by 4 h of reperfusion. Furthermore, the α2-adrenergic receptor (α2-AR) antagonist, yohimbine, was administered in wild-type C57BL/6N mice intestinal I/R model to investigate the role of α2-AR in the intestinal protection conferred by DEX. Results: In the present study, we identified intestinal I/R-induced obvious inflammation, endoplasmic reticulum (ER) stress-dependent apoptosis, and oxidative stress, and all the aforementioned changes were improved by the administration of DEX. PDIA3 cKO in the intestinal epithelium have reversed the protective effects of DEX. Moreover, yohimbine also reversed the intestinal protection of DEX and downregulated the messenger RNA and protein levels of PDIA3. Conclusion: DEX prevents PDIA3 decrease by activating α2-AR to inhibit intestinal I/R-induced inflammation, ER stress-dependent apoptosis, and oxidative stress in mice.

The Effects of Dexmedetomidine on Abdominal Aortic Occlusion-Induced Ovarian Injury via Oxidative Stress and Apoptosis

“…It is of great importance to protect the ovaries from I/R damage for the continuation of fertilization and oocyte maturation. The purpose of the present study was therefore to investigate the effects on ovarian I/R injury of DEX, which has been shown to exhibit antiapoptotic, anti-inflammatory, and antioxidant effects in tissues such as the brain, kidney, intestine, and testis, as well as beneficial effects on the cardiovascular and respiratory systems in several previous studies [Qiu et al, 2018;Tan et al, 2018;Shi et al, 2019;Wang et al, 2019;Zhang et al, 2021b;Weng et al, 2021;Zhan et al, 2022;Zhao et al, 2022].…”