He Li1, Ouyang Chen1, Zhouheng Ye2, Rongjia Zhang2, Huijun Hu3, Ning Zhang2, Junlong Huang2, Wenwu Liu4, Xuejun Sun5. 1. Department of Navy Aviation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, People's Republic of China; Department of Clinical Medicine, Second Military Medical University, Shanghai 200433, People's Republic of China. 2. Department of Navy Aviation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, People's Republic of China. 3. Navy General Hospital, Beijing 100048, People's Republic of China. 4. Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, People's Republic of China. Electronic address: liuwenwu1980@hotmail.com. 5. Department of Navy Aviation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, People's Republic of China. Electronic address: sunxjk@hotmail.com.
Abstract
BACKGROUND AND AIMS: This study explored the hepatoprotection of high concentrations of hydrogen (HCH) inhalation in a mouse hepatic ischemia/reperfusion (I/R) injury model and the potential mechanism. METHODS: To explore the role of the PI3K-Akt pathway in the hepatoprotection of HCH, C57BL/6 mice were randomly divided into five groups: Sham, I/R, I/R+HCH, LY294002 (PI3K inhibitor)+I/R+HCH, and LY+I/R groups. Mice received inhalation of 66.7% hydrogen and 33.3% oxygen for 1h immediately after surgery. LY294002 was intravenously injected at 10mol/kg. To explore whether PI3K-Akt pathway activation was mediated by the A2A receptor, additional four groups were included: ZM241385 (A2A receptor antagonist)+I/R+HCH, ZM241385+I/R, bpv(HOpic) (PTEN inhibitor)+I/R, and ZM241385+bpv+I/R+HCH. Six hours after I/R, serum biochemistry, histological examination, Western blotting, and immunohistochemistry were performed to evaluate the hepatoprotection of HCH and the role of the PI3K-Akt pathway and A2A receptor in this protection. RESULTS: Liver dysfunction, hepatic pathological injury, infiltration of inflammatory cytokines, and hepatocyte apoptosis were observed after hepatic I/R, accompanied by inhibition of the PI3K-Akt pathway. HCH significantly improved liver function, reduced serum inflammatory cytokines, and inhibited hepatocyte apoptosis, and also induced the PI3K-Akt pathway activation. In the presence of LY294002 or ZM241385, the protective effects of HCH were markedly attenuated, but the effects of ZM241385 were reversed by bpv(HOpic). CONCLUSION: Our findings indicate that HCH may protect the liver against I/R injury through the A2A dependent PI3K-Akt pathway.
BACKGROUND AND AIMS: This study explored the hepatoprotection of high concentrations of hydrogen (HCH) inhalation in a mousehepatic ischemia/reperfusion (I/R) injury model and the potential mechanism. METHODS: To explore the role of the PI3K-Akt pathway in the hepatoprotection of HCH, C57BL/6 mice were randomly divided into five groups: Sham, I/R, I/R+HCH, LY294002 (PI3K inhibitor)+I/R+HCH, and LY+I/R groups. Mice received inhalation of 66.7% hydrogen and 33.3% oxygen for 1h immediately after surgery. LY294002 was intravenously injected at 10mol/kg. To explore whether PI3K-Akt pathway activation was mediated by the A2A receptor, additional four groups were included: ZM241385 (A2A receptor antagonist)+I/R+HCH, ZM241385+I/R, bpv(HOpic) (PTEN inhibitor)+I/R, and ZM241385+bpv+I/R+HCH. Six hours after I/R, serum biochemistry, histological examination, Western blotting, and immunohistochemistry were performed to evaluate the hepatoprotection of HCH and the role of the PI3K-Akt pathway and A2A receptor in this protection. RESULTS:Liver dysfunction, hepatic pathological injury, infiltration of inflammatory cytokines, and hepatocyte apoptosis were observed after hepatic I/R, accompanied by inhibition of the PI3K-Akt pathway. HCH significantly improved liver function, reduced serum inflammatory cytokines, and inhibited hepatocyte apoptosis, and also induced the PI3K-Akt pathway activation. In the presence of LY294002 or ZM241385, the protective effects of HCH were markedly attenuated, but the effects of ZM241385 were reversed by bpv(HOpic). CONCLUSION: Our findings indicate that HCH may protect the liver against I/R injury through the A2A dependent PI3K-Akt pathway.
Authors: Lei Huang; Richard L Applegate Ii; Patricia M Applegate; Lei Gong; Umut Ocak; Warren Boling; John H Zhang Journal: Med Gas Res Date: 2019 Jul-Sep