藥物誘導脂肪間葉細胞微囊泡非解碼核糖核酸體作為腎缺血再灌流傷害治療策略之評估

Transplantation of adipose-derived stem cells may reduce renal ischemia/reperfusion induced tubular oxidative stress, apoptosis, autophagy and renal dysfunction. We suggest that pharmacological preconditioning adipose-derived stem cells-microvesicles may confer further protection against renal ischemia/reperfusion injury through microRNA mechanisms. Preconditioning adipose-derived stem cells with dexmedetomidine triggered higher migration capability than empagliflozin and N-acetylcysteine. Treatment of sonicating dexmedetomidine treated adipose-derived stem cells-microvesicles significantly preserved microcirculation and renal blood flow and decreased tubular injury score, pNF-κB-mediated inflammation, Beclin-1 mediated autophagy and caspase 3/poly (ADP-ribose) polymerase mediated apoptosis, blood urea nitrogen and creatinine levels vs. ischemia/reperfusion kidney and adipose-derived stem cells-microvesciles treated kidney. Post-ischemia/reperfusion kidneys had higher levels of miR-122-5p expression and lower levels of miR-543-3p expression vs. control kidney. Dexmedetomidine treated adipose-derived stem cells-microvesicles treatment significantly preserved ischemia/reperfusion altered miR-122-5p and miR-543-3p expression in the ischemia/reperfusion kidney. In the HOCl injuried NRK52E cells, exogenous miR-122-5p mimics exacerbated and miR-543-3p mimics ameliorated Bax/Bcl-2 mediated apoptosis and Beclin-1 mediated autophagy. In conclusion, upregulation of miR-122-5p expression and downregulation of miR-543-3p in the post-ischemia/reperfusion kidney may contribute a role in tubular cell apoptosis and autophagy and renal dysfunction. Dexmedetomidine treated adipose-derived stem cells-microvesicles reduced renal ischemia/reperfusion injury through restoring miR-122-5p and miR-543-3p mediated apoptosis and autophagy.