Progesterone alleviates hypoxic‑ischemic brain injury via the Akt/GSK‑3β signaling pathway

Li,Xiaojuan; Zhang,Junhe; Chai,Shujie; Wang,Xiaoyin

doi:10.3892/etm.2014.1858

Progesterone alleviates hypoxic‑ischemic brain injury via the Akt/GSK‑3β signaling pathway

Authors:
- Xiaojuan Li
- Junhe Zhang
- Shujie Chai
- Xiaoyin Wang
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Affiliations: Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China, Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China, Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China
Published online on: July 21, 2014 https://doi.org/10.3892/etm.2014.1858
Pages: 1241-1246

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Abstract

This aim of this study was to investigate whether progesterone (PROG) alleviates the neuronal apoptosis in neonatal rats with hypoxic‑ischemic (HI) brain damage through the phosphatidylinositol 3‑kinase (PI3K)/Akt/glycogen synthase kinase‑3β (GSK‑3β) signaling pathway. A total of 96 newborn Wistar rats aged 7 days were randomly divided into four groups: sham surgery, HI, drug prevention (PROG) and Akt inhibitor groups. HI animal models were established by a conventional method. All animals were sacrificed 24 h after hypoxia. Immunohistochemistry was used to detect the distribution and expression of phosphorylated Akt (p‑Akt) and the GSK‑3β proteins in the brain, and western blot analysis was used to determine the p‑Akt and GSK‑3β protein contents. An enzyme‑linked immunosorbent assay was also used to determine the GSK‑3β content of the brain tissue, and flow cytometry was used to evaluate the apoptosis rate of neural cells. The expression of p‑Akt protein was reduced in the brain tissues of the HI group, whereas GSK‑3β expression was increased. In addition, the GSK‑3β content of the brain and the neuronal apoptosis rate were significantly increased. PROG pre‑treatment increased p‑Akt expression, decreased GSK‑3β expression and GSK‑3β content, and also reduced neuronal apoptosis. Following administration of the Akt inhibitor wortmannin, p‑Akt expression decreased, GSK‑3β expression increased, and the GSK‑3β content and neuronal apoptosis rate significantly increased (P<0.05). In conclusion, PROG activates the PI3K/Akt/GSK‑3β pathway to promote Akt activation, enhance p‑Akt expression and inhibit GSK‑3β expression, thereby inhibiting neuronal apoptosis, alleviating HI brain injury and inducing a cerebroprotective effect.

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