Duan Chenyang, Chen Ken, Yang Guangming, Li Tao, Liu Liangming
State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University Chongqing 400042, China.
Am J Transl Res. 2017 Mar 15;9(3):1277-1286. eCollection 2017.
HIF-1α plays an essential role in hemorrhagic shock-induced vasoconstriction. However, the underlying mechanisms remain poorly understood. Here, we studied both the role of HIF-1α in regulating vasodilatation, and the involvement of Cx40 in this process. We found that endothelium-dependent vasodilatation exhibited an overall decline after hemorrhagic shock: at the beginning of shock vasodilatation reactivity significantly decreased, followed by a slight increase from 0.5 h to 2 h after shock. After 2 h vasodilatation dropped again. Throughout this process, protein levels of HIF-1α gradually increased. In the late period of shock, vasodilatation reactivity was enhanced by oligomycin, an HIF-1α inhibitor, suggesting that HIF-1α may promote vasoconstriction. Moreover, in the late period of shock Cx40 levels gradually increased and exhibited a negative correlation with endothelium-dependent vasoconstriction reactivity. Furthermore, Cx40 AODN significantly improved vasoconstriction reactivity and could be regulated by either an HIF-1α inhibitor or an agonist. Together, these data suggest that HIF-1α may inhibit endothelium-dependent vasodilatation reactivity following hemorrhagic shock by up-regulating Cx40, especially in the late period of shock.
缺氧诱导因子-1α（HIF-1α）在失血性休克诱导的血管收缩中起重要作用。然而，其潜在机制仍知之甚少。在此，我们研究了HIF-1α在调节血管舒张中的作用以及Cx40在此过程中的参与情况。我们发现失血性休克后内皮依赖性血管舒张总体下降：休克开始时血管舒张反应性显著降低，随后在休克后0.5小时至2小时略有增加。2小时后血管舒张再次下降。在整个过程中，HIF-1α的蛋白水平逐渐升高。在休克后期，HIF-1α抑制剂寡霉素可增强血管舒张反应性，提示HIF-1α可能促进血管收缩。此外，在休克后期Cx40水平逐渐升高，且与内皮依赖性血管收缩反应性呈负相关。此外，Cx40反义寡脱氧核苷酸（AODN）可显著改善血管收缩反应性，且其可受HIF-1α抑制剂或激动剂调节。总之，这些数据表明，HIF-1α可能通过上调Cx40抑制失血性休克后内皮依赖性血管舒张反应性，尤其是在休克后期。
