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Mol Med Rep. 2018 Nov 27. doi: 10.3892/mmr.2018.9699. [Epub ahead of print]

A SIRT1 agonist reduces cognitive decline in type 2 diabetic rats through antioxidative and anti‑inflammatory mechanisms.

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Health Management Institute, Chinese PLA General Hospital, Beijing 100853, P.R. China.
Department of Geriatric Neurology, Chinese PLA General Hospital, Beijing 100853, P.R. China.


Sirtuin 1 (SIRT1) is an NAD+‑dependent protein deacetylase that is involved in cell differentiation, aging, apoptosis, physiological rhythms, metabolic regulation, oxidative stress and numerous other important biological processes. In the present study, the ability of a sirtuin‑1 (SIRT1) agonist, SRT1720, to reduce cognitive decline in type 2 diabetes mellitus (T2DM) was investigated. Streptozotocin‑induced male Sprague‑Dawley rats were used to establish a T2DM model and the protective effect of SRT1720 and its underlying mechanisms were investigated. Body weight and fasting blood glucose (FBG) were recorded and cognitive function was measured with the Morris water maze. Levels of oxidative stress, inflammation, caspase‑3 activity and nuclear factor κB (NF‑κB) mRNA expression were detected with a series of commercial assay kits and reverse transcription‑quantitative polymerase chain reaction, respectively. Western blot analysis was performed to determine the protein expression of NF‑κB, endothelial nitric oxide synthase (eNOS), peroxisome proliferator‑activated receptor γ (PPARγ), AMP‑activated protein kinase (AMPK), heat shock 70 kDa protein (HSP70), SIRT1, nuclear factor erythroid 2‑related factor 2 (Nrf2) and heme oxygenase 1 (HO‑1). The results revealed that SRT1720 significantly increased body weight, decreased FBG, improved cognitive function and reduced the levels of proteins associated with oxidative stress and inflammation damage in T2DM rats. Additionally, SRT1720 significantly decreased NF‑κB p65 mRNA expression and increased eNOS and PPARγ expression. SRT1720 significantly reduced caspase‑3 activity and HSP70 protein expression, and increased p‑AMPK, SIRT1, Nrf2 and HO‑1 protein expression. Collectively, the results indicate that SRT1720 may reduce cognitive decline in T2DM rats through antioxidative and anti‑inflammatory action via NF‑κB and AMPK‑dependent mechanisms.


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