Ghrelin attenuates brain injury in septic mice via PI3K/Akt signaling activation.
Brain injury has been reported to occur in sepsis and can lead to high mortality among septic patients. Previous studies suggest that ghrelin is protective for the brain, but whether ghrelin protects brain from sepsis remains unclear. Therefore, the aim of this study is to investigate the protective effect of ghrelin against sepsis-induced brain injury. Cecal ligation and puncture was performed in male C57BL/6J mice to establish the sepsis model. Ghrelin was administrated intraperitoneally at a dose of 80μg/kg. The blood-brain barrier (BBB) integrity, brain water content, inflammatory cytokines (TNF-α and IL-1β), oxidative stress (SOD and MDA) and neuronal apoptosis were assessed. In addition, the expression levels of Akt, phospho-Akt (Ser473) (p-Akt), Bcl-2 and Bax were detected by Western blot. Our results suggested that ghrelin attenuated brain edema, neuronal apoptosis and enhanced BBB integrity. Ghrelin decreased the production of TNF-α and IL-1β. Ghrelin increased the activity of SOD and decreased MDA production. Additionally, ghrelin increased the expression of p-Akt and Bcl-2 and decreased the Bax expression. The protective effects of ghrelin mentioned above were abolished by LY294002 (LY), a PI3K inhibitor. In conclusion, our results demonstrate that ghrelin attenuates brain injury in sepsis via PI3K/Akt signaling activation.
Department of Geriatrics, Tianjin Geriatrics Institute Tianjin, Tianjin Medical University General Hospital, China.
Ning
N
Sun
Department of Geriatrics, Tianjin Geriatrics Institute Tianjin, Tianjin Medical University General Hospital, China.
Hui
H
Wang
Department of Geriatrics, Tianjin Geriatrics Institute Tianjin, Tianjin Medical University General Hospital, China.
Li
L
Ma
Department of Geriatrics, Tianjin Geriatrics Institute Tianjin, Tianjin Medical University General Hospital, China. Electronic address: leipingtmu@sina.com.
Ping
P
Lei
Department of Geriatrics, Tianjin Geriatrics Institute Tianjin, Tianjin Medical University General Hospital, China. Electronic address: zhangq766@sina.com.
Qiang
Q
Zhang
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology; D002199:Capillary Permeability / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054439:Ghrelin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018805:Sepsis / Q000150:complications; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D002867:Chromones; D016207:Cytokines; D004791:Enzyme Inhibitors; D054439:Ghrelin; D009025:Morpholines; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D013482:Superoxide Dismutase; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt
Cecal ligation and puncture; Ghrelin; PI3K/Akt signaling; Sepsis