Low‑dose lipopolysaccharide inhibits neuronal apoptosis induced by cerebral ischemia/reperfusion injury via the PI3K/Akt/FoxO1 signaling pathway in rats

He,Fan; Zhang,Nannan; Lv,Yan; Sun,Wenhao; Chen,Huisheng

doi:10.3892/mmr.2019.9827

Low‑dose lipopolysaccharide inhibits neuronal apoptosis induced by cerebral ischemia/reperfusion injury via the PI3K/Akt/FoxO1 signaling pathway in rats

Authors:
- Fan He
- Nannan Zhang
- Yan Lv
- Wenhao Sun
- Huisheng Chen
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Affiliations: Department of Neurology, General Hospital of Shenyang Military Area Command, Shenyang, Liaoning 110016, P.R. China, Department of Neurology, The General Hospital of Tianjin Medical University, Tianjin 300020, P.R. China
Published online on: January 7, 2019 https://doi.org/10.3892/mmr.2019.9827
Pages: 1443-1452
Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the effects of low‑dose lipopolysaccharide (LPS) on ischemia/reperfusion (I/R)‑induced brain injury, and to explore the mechanism of phosphoinositide 3‑kinase (PI3K)/Akt/forkhead box protein (Fox)O1 signaling pathway. Male Sprague‑Dawley rats were divided into control group (control), ischemia/reperfusion surgery group (I/R) and low‑dose LPS treatment group (LPS). An I/R model was established and the hemodynamic parameters were recorded at the end of I/R injury. The brain tissues were observed by hematoxylin and eosin staining, immunohistochemistry and terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling staining. Microglia were treated with LPS following hypoxia/reoxygenation. The cellular viability was detected by 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay. The apoptotic rate of microglia was detected using AnnexinV/propidium iodide staining. The expression of B‑cell lymphoma (Bcl)‑2, Bcl‑2‑associated X (Bax), and caspase‑3 were detected by western blot analysis and reverse transcription‑quantitative polymerase chain reaction. Akt, phosphorylated (p)‑Akt, FoxO1 and p‑FoxO1 expression were detected by western blotting. It was previously reported that, following I/R injury, neuronal cells were disorderly and brain injury markers (neuron‑specific enolase and S100 β), inflammatory cytokines [interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α] levels were significantly upregulated. In the present study, the expression levels of Bax, caspase‑3 Akt and p‑Akt were significantly higher, while that of Bcl‑2, FoxO1 and p‑FoxO1 were significantly lower in the I/R group. LPS treatment significantly increased the viability of neuronal cells and decreased the rate of neuronal cell apoptosis. Following the addition of PI3K signaling pathway inhibitor LY294002 to microglia, LPS reduced the levels of activated Akt, increased the downstream regulatory gene phosphorylation of FoxO1 and reduced microglia apoptosis. It was concluded that LPS can alleviate I/R‑induced brain injury, inhibit neuronal cells apoptosis and protect neuronal cells via the PI3K/Akt/FoxO1 signaling pathway.

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