Effects of mTOR/NF-κB signaling pathway and high thoracic epidural anesthesia on myocardial ischemia-reperfusion injury via autophagy in rats

J Cell Physiol. 2018 Sep;233(9):6669-6678. doi: 10.1002/jcp.26320. Epub 2018 Mar 25.

Abstract

We investigated the role of mammalian target of rapamycin/nuclear factor-kappa B (mTOR/NF-κB) signaling pathway in high thoracic epidural anesthesia (HTEA) against myocardial ischemia-reperfusion (I/R) injury in rats. The rat model of myocardial I/R injury was established. Ninety rats were divided into the normal, sham, I/R, eHTEA, the PDTC, and HTEA + PDTC groups. ELISA was applied to detect cardiac function indexes. HE staining was conducted to observe histopathological changes of myocardial tissues, and TTC staining was performed to detect the myocardial infarction size. TUNEL staining was adopted to detect the cell apoptosis rate. The mRNA and protein levels of mTOR, NF-κB, Fasl, Bcl-2 and Bax, and LC3-I, LC3-II, BNIP3, and Atg5 were detected by RT-qPCR and Western blotting, respectively. The findings indicated that compared with the normal and sham groups, the I/R, PDTC, and HTEA groups showed the larger myocardial infarction size and increased cell apoptosis rate, while the results in the HTEA + PDTC group were opposite. Compared with the normal and sham groups, the I/R group showed reduced mRNA and protein levels of Bcl-2, LC3, BNIP3, and Atg5, and elevated mRNA and protein levels of mTOR, p50, p65, Bax, and Fasl, while the HTEA + PDTC group revealed the opposite results, and the PDTC and HTEA group revealed the increased mRNA and protein levels of Bcl-2, LC3, BNIP3, Atg5, mTOR, p50, p65, Bax, and Fasl. These results prove that the inhibition of mTOR/NF-κB signaling pathway potentiates HTEA against myocardial IR injury by autophagy and apoptosis in rats.

Keywords: autophagy; high thoracic epidural anesthesia; mTOR/NF-κB signaling pathway; myocardial ischemia reperfusion injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Anesthesia, Epidural / methods
  • Anesthetics / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Autophagy / drug effects*
  • Male
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism*
  • Myocardial Reperfusion Injury / drug therapy*
  • Myocardial Reperfusion Injury / metabolism*
  • Myocardium / metabolism
  • NF-kappa B / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • TOR Serine-Threonine Kinases / metabolism*
  • Thoracic Vertebrae / drug effects
  • Thoracic Vertebrae / metabolism

Substances

  • Anesthetics
  • NF-kappa B
  • RNA, Messenger
  • mTOR protein, rat
  • TOR Serine-Threonine Kinases