Hydrogen-Rich Saline Attenuates Brain Injury Induced by Cardiopulmonary Bypass and Inhibits Microvascular Endothelial Cell Apoptosis Via the PI3K/Akt/GSK3β Signaling Pathway in Rats
| Autor: | Xiuying Wu, YingJie Sun, Keyan Chen, Yugang Diao, Nan Wang, Lidan Liu, Wanwei Dong |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Physiology Inflammation Apoptosis Pharmacology PI3K/Akt/GSK3β Signaling Pathway Sodium Chloride lcsh:Physiology lcsh:Biochemistry Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Phosphatidylinositol 3-Kinases 0302 clinical medicine Western blot medicine Animals lcsh:QD415-436 Protein kinase B PI3K/AKT/mTOR pathway Evans Blue Hydrogen-Rich Saline Cardiopulmonary Bypass Glycogen Synthase Kinase 3 beta medicine.diagnostic_test lcsh:QP1-981 Chemistry Brain Endothelial Cells 030104 developmental biology 030220 oncology & carcinogenesis Brain Injuries Phosphorylation medicine.symptom Signal transduction Proto-Oncogene Proteins c-akt Hydrogen Signal Transduction |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 43, Iss 4, Pp 1634-1647 (2017) |
| ISSN: | 1421-9778 |
| Popis: | Background/Aims: Cardiopulmonary bypass (CPB) is prone to inducing brain injury during open heart surgery. A hydrogen-rich solution (HRS) can prevent oxidation and apoptosis, and inhibit inflammation. This study investigated effects of HRS on brain injury induced by CPB and regulatory mechanisms of the PI3K/Akt/GSK3β signaling pathway. Methods: A rat CPB model and an in vitro cell hypoxia model were established. After HRS treatment, Rat behavior was measured using neurological deficit score; Evans blue (EB) was used to assess permeability of the blood-brain barrier (BBB); HE staining was used to observe pathological changes; Inflammatory factors and brain injury markers were detected by ELISA; the PI3K/Akt/GSK3β pathway-related proteins and apoptosis were assessed by western blot, immunohistochemistry and qRT –PCR analyses of brain tissue and neurons. Results: After CPB, brain tissue anatomy was disordered, and cell structure was abnormal. Brain tissue EB content increased. There was an increase in the number of apoptotic cells, an increase in expression of Bax and caspase-3, a decrease in expression of Bcl2, and increases in levels of Akt, GSK3β, P-Akt, and P-GSK3β in brain tissue. HRS treatment attenuated the inflammatory reaction ,brain tissue EB content was significantly reduced and significantly decreased expression levels of Bax, caspase-3, Akt, GSK3β, P-Akt, and P-GSK3β in the brain. After adding the PI3K signaling pathway inhibitor, LY294002, to rat cerebral microvascular endothelial cells (CMECs), HRS could reduce activated Akt expression and downstream regulatory gene phosphorylation of GSK3β expression, and inhibit CMEC apoptosis. Conclusion: The PI3K/Akt/GSK3β signaling pathway plays an important role in the mechanism of CPB-induced brain injury. HRS can reduce CPB-induced brain injury and inhibit CMEC apoptosis through the PI3K/Akt/GSK3β signaling pathway. |
| Databáze: | OpenAIRE |
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