氦气预适应通过A2aR/Src/PI3k/Akt通路保护肝脏缺血再灌注损伤的研究

Helium preconditioning (HPC) can protect against ischemic stress in myocardia and neuronal tissues. However, the question of whether HPC can decrease ischemia and reperfusion (I/R) injury to other organs and the mechanisms of HPC remain unclear. We demonstrated: 1) HPC reduces severity of I/R induced liver injury in mice; 2) the PI3k/Akt pathways plays an essential role in the protective effects of HPC in hepatic I/R injury; 3) most of HPC-induced pAkt positive cells are hepatocytes but not Kupffer cells; 4) A2aR plays an important role in mediating HPC-induced PI3k/Akt activation and liver protection. Accordingly, we propose the following: HPC may attenuate hepatic I/R injury via the activation of A2aR/Src/PI3k/Akt pathway in hepatocytes. To prove the hypothesis, the project intends to conduct the following studies: 1) to complete the animal studies on the expression of A2aR/Src after HPC; 2) to clarify the protective effect of HPC via PI3k/Akt pathways on ODG/R model; 3) to demonstrate HPC-induced activation of A2aR/Src channel on ODG/R model. The aim of this study is to reveal the protective effect of HPC on I/R-induced liver injury and the role of A2aR/Src/PI3k/Akt pathway in the protection in vivo and in vitro.

氦气预适应（HPC）可以对心脏和大脑的缺血再灌注（I/R）损伤具有保护作用，但是其对肝脏的I/R损伤和机制尚无报道。我们发现：1）HPC可以保护小鼠的肝脏I/R损伤；2）HPC对肝脏的保护是通过激活PI3k/Akt通路；3）HPC激活的pAkt主要表达在肝细胞而非库否氏细胞上；4）A2aR参与HPC对pAkt的激活和肝脏的保护作用。据此，我们设想：HPC通过激活肝细胞的A2aR/Src/PI3k/Akt通路保护肝脏的I/R损伤。我们拟进行如下研究：1）在小鼠肝I/R模型中，证明HPC可激活A2aR/Scr通路；2）在体外肝细胞OGD/R模型中，证明HPC可以激活PI3k/Akt提高肝细胞缺氧耐受能力；3）在肝细胞OGD/R模型中，证明HPC可激活A2aR/Src调控PI3k/Akt通路。最终从体内外实验证实HPC通过激活肝细胞A2aR/Src/PI3k/Akt保护肝脏I/R损伤

氦气预适应（HPC）可以对心脏和大脑的缺血再灌注损伤（I/R）具有保护作用，但是其对肝脏I/R损伤和机制尚无报道。我们发现：1、在体内实验，HPC可以通过A2aR/Src/Pi3k/Akt通路保护小鼠肝脏I/R损伤；2、在体外实验，HPC同样通过A2aR/Src/Pi3k/Akt通路保护肝细胞糖氧剥夺（OGD/R）损伤。我们实验证明HPC可以激活肝脏中的A2aR/Src/Pi3k/Akt通路从而免受I/R损伤。此外，我们额外进行了HPC对减压病（DCS）的初步研究，发现HPC对DCS也具有一定的保护作用，拓展了HPC其他军事医学领域应用的可能性。