Sirt1/Nrf2 signalling pathway prevents cognitive impairment in diabetic rats through anti‑oxidative stress induced by miRNA‑23b‑3p expression

Mol Med Rep. 2018 Jun;17(6):8414-8422. doi: 10.3892/mmr.2018.8876. Epub 2018 Apr 12.

Abstract

In the present study the exact roles and mechanisms underlying the effect of miRNA‑23b‑3p on the cognitive impairment of diabetic rats were investigated. The in vivo model of diabetes was established in Wistar rats via a single injection of streptozotocin (STZ). Cognitive function was evaluated using a Morris water maze test. Oxidative stress was measured using ELISA kits, and the protein expression levels of B‑cell lymphoma 2‑associated X protein, silent information regulator 1 (SIRT1), nuclear factor erythroid 2‑related factor 2 (Nrf2) and GAPDH were measured by western blot analysis. Micro (mi)RNA‑23b‑3p mimics were employed to increase miRNA‑23b‑3p expression in the in vitro model. Overexpression of miRNA‑23b‑3p increased oxidative stress (as indicated by the levels of glutathione peroxidase, glutathione, superoxide dismutase and malondialdehyde) and apoptosis in neurocytes following high‑glucose treatment. The overexpression of miRNA‑23b‑3p also suppressed SIRT1 and Nrf2 expression in neurocytes following high‑glucose treatment; it also promoted the SIRT1‑induced inhibition of apoptosis and oxidative stress. The promotion of SIRT1 also decreased the effect of miRNA‑23b‑3p on cognitive impairment in diabetic rats. In conclusion, miRNA‑23b‑3p prevents the cognitive impairment of diabetic rats via anti‑oxidative stress effects and the Sirt1/Nrf2 signaling pathway.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Proliferation
  • Cognitive Dysfunction / etiology*
  • Cognitive Dysfunction / metabolism*
  • Cognitive Dysfunction / psychology
  • Diabetes Mellitus, Experimental
  • Gene Expression
  • Gene Expression Regulation*
  • Glucose / metabolism
  • Male
  • Maze Learning
  • MicroRNAs / genetics*
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress* / genetics
  • Rats
  • Signal Transduction*
  • Sirtuin 1 / metabolism

Substances

  • MicroRNAs
  • NF-E2-Related Factor 2
  • Sirtuin 1
  • Glucose