p38 mitogen-activated protein kinase gene silencing rescues rat hippocampal neurons from ketamine-induced apoptosis: An in vitro study

Guo,Xiao‑Qian; Cao,Yu‑Ling; Zhao, Li; Zhang,Xuan; Yan,Zhong‑Rui; Chen,Wei‑Mei

doi:10.3892/ijmm.2018.3750

p38 mitogen-activated protein kinase gene silencing rescues rat hippocampal neurons from ketamine-induced apoptosis: An in vitro study

Authors:
- Xiao‑Qian Guo
- Yu‑Ling Cao
- Li Zhao
- Xuan Zhang
- Zhong‑Rui Yan
- Wei‑Mei Chen
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Affiliations: Department of Neurology, Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China
Published online on: June 29, 2018 https://doi.org/10.3892/ijmm.2018.3750
Pages: 1401-1410
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ketamine (KTM) is an anesthetic drug with several advantages, including the elevation of cardiac output and blood pressure. However, KTM may also induce the apoptosis of hippocampal neurons. Notably, p38 mitogen‑activated protein kinase (p38MAPK) has previously been studied for its role in neuronal injury. Therefore, the present study evaluated the effect of lentivirus‑mediated p38MAPK gene silencing on KTM‑induced apoptosis of rat hippocampal neurons. Hippocampal neurons were extracted from neonatal Sprague‑Dawley rats, and then treated with KTM, p38MAPK‑short hairpin RNA or SB203580 (an inhibitor of p38MAPK). Next, the expression levels of p38MAPK and apoptosis‑associated genes, including caspase‑3, B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax), were detected. In addition, cell viability and apoptosis were determined using an MTT assay and flow cytometry, respectively. Finally, telomerase activity of hippocampal neurons was detected by ELISA. The results revealed that silencing of p38MAPK in KTM‑treated cells decreased the expression levels of p38MAPK, caspase‑3 and Bax, and the extent of p38MAPK phosphorylation, while it increased the expression of Bcl‑2. Furthermore, silencing p38MAPK promoted cell viability, cell cycle progression and the telomerase activity of hippocampal neurons, and inhibited the apoptosis of hippocampal neurons. Taken together, the results suggested an inhibitory role of lentivirus‑mediated p38MAPK gene silencing on KTM‑induced apoptosis of rat hippocampal neurons. Thus, p38MAPK gene silencing may serve as a potential target for preventing the KTM‑induced apoptosis of hippocampal neurons.

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