Sufentanil attenuates renal ischemia-reperfusion injury via the lncRNA KCNQ1OT1/miR-211-5p/HMGB1 axis.

in Pathology, research and practice by Meihua Lin, Xi Wu, Shuang Zhang

TLDR

  • Sufentanil has protective effects on renal ischemia-reperfusion injury by reducing inflammation and promoting cell survival, and its mechanisms involve inhibiting the TLR4/MyD88/NF-κB pathway.

Abstract

Inflammation is one of the most significant pathological changes in ischemia-reperfusion injury (IRI). Sufentanil has protective effects on IRI by reducing inflammatory responses. This study aimed to investigate the protective effects and possible mechanisms of sufentanil on renal IRI (RIRI). In this study, sufentanil inhibited hypoxia/reoxygenation (H/R)-treated HK-2 proliferation and apoptosis, decreased cleaved caspase3 and increased B-cell Lymphoma 2 (Bcl-2) protein expression, inhibited reactive oxygen species (ROS) generation, and reduced inflammatory factor secretion. Moreover, sufentanil inhibited KCNQ1 overlapping transcript 1 (KCNQ1OT1) expression in H/R-treated HK-2 cells, and pcDNA-KCNQ1OT1 reversed the cell protective effects of sufentanil, whereas miR-211-5p inhibitor here reversed the effects of pcDNA-KCNQ1OT1. Furthermore, miR-211-5p targets the 3'UTR of high mobility group box1 (HMGB1), and HMGB1 reversed the inhibitory effects of miR-211-5p mimic or sufentanil on cell proliferation, apoptosis, oxidative stress, and inflammation. Mechanistic studies revealed that sufentanil alleviated H/R-treated HK-2 cell injury was mediated by inhibiting the toll like receptor 4 (TLR4)/ myeloid differentiation factor 88 (MyD88)/ nuclear factor kappa B (NF-κB) pathway. In renal ischemia-reperfusion (I/R) rats, sufentanil inhibited KCNQ1OT1, HMGB1 and cleaved caspase3 expression, promoted miR-211-5p expression and alleviated inflammatory infiltration in renal tissues.

Overview

  • The study investigated the protective effects of sufentanil on renal ischemia-reperfusion injury (RIRI) by reducing inflammatory responses.
  • Sufentanil inhibited hypoxia/reoxygenation-treated HK-2 cell proliferation and apoptosis, decreased cleaved caspase3 and increased Bcl-2 protein expression, and reduced inflammatory factor secretion.
  • The study aimed to explore the underlying mechanisms of sufentanil's protective effects, including its effects on KCNQ1OT1 expression, miR-211-5p, and HMGB1 protein expression, as well as its inhibitory effects on the TLR4/MyD88/NF-κB pathway.

Comparative Analysis & Findings

  • The results showed that sufentanil inhibited KCNQ1OT1 expression in H/R-treated HK-2 cells and reversed the cell protective effects of sufentanil.
  • The study found that pcDNA-KCNQ1OT1 reversed the cell protective effects of sufentanil, whereas miR-211-5p inhibitor reversed the effects of pcDNA-KCNQ1OT1.
  • Sufentanil also inhibited HMGB1 expression and alleviated the inhibitory effects of miR-211-5p mimic or sufentanil on cell proliferation, apoptosis, oxidative stress, and inflammation.

Implications and Future Directions

  • The study suggests that sufentanil may be a potential therapeutic agent for the treatment of RIRI by reducing inflammation and promoting cell survival.
  • Future studies should investigate the specific mechanisms by which sufentanil exerts its protective effects and identify the potential biomarkers for predicting treatment outcomes.
  • Additionally, clinical trials are needed to confirm the safety and efficacy of sufentanil in human patients with RIRI.
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