Kinoshita Hiroyuki, Watanabe Kazushi, Azma Toshiharu, Feng Guo-Gang, Akahori Takahiko, Hayashi Hisaki, Sato Motohiko, Fujiwara Yoshihiro, Wakatsuki Akihiko
Departments of Anesthesiology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi 480-1195, Japan.
Obstetrics and Gynecology, Aichi Medical University School of Medicine, 1-1 Yazako Karimata, Nagakute, Aichi 480-1195, Japan.
Heliyon. 2017 Aug 2;3(8):e00369. doi: 10.1016/j.heliyon.2017.e00369. eCollection 2017 Aug.
The present study to address one of the mechanisms in preeclampsia, examined whether levels of oxidative stress, human serum albumin, and endothelial function correlate in pregnant women and whether human serum albumin reduces levels of superoxide produced by NADPH oxidase activation in the human vascular smooth muscle cells.
Pregnant women with (Preeclampsia group, n = 33) and without preeclampsia (Normal group, n = 37) were recruited to determine levels of reactive oxygen species (serum diacron-reactive oxygen metabolite [d-ROM]), and the flow-mediated dilation (FMD). Human coronary arterial smooth muscle cells or omental arteries were subjected to evaluate isometric force recordings, levels of superoxide, western immunoblotting, and immunohistochemistry. The superoxide scavenging assay was also performed in a cell-free system.
Women in the preeclampsia group demonstrated lower FMD and higher serum d-ROM values than those in the normal group. There were the inverse correlations between serum levels of d-ROM and the degree of FMD and between serum levels of albumin and those of d-ROM. D-glucose reduced the levcromakalim-induced dilation of human omental arteries, and it increased levels of superoxide and the recruitment of the NADPH oxidase subunit p47phox in human coronary arterial smooth muscle cells. Human serum albumin (0.05 to 0.5 g/dL) prevented these alterations whereas it exerted no superoxide scavenging effect.
Serum albumin relates to oxidative stress inversely, but to the endothelial function positively, in pregnant women. Human serum albumin appears to reduce oxidative stress via NADPH oxidase inhibition in the human vascular smooth muscle, indicating that the serum level may be a critical determinant of vascular oxidative stress in some human diseases.
本研究旨在探讨子痫前期的发病机制之一,研究孕妇体内氧化应激水平、人血清白蛋白水平与内皮功能之间是否存在相关性,以及人血清白蛋白是否能降低人血管平滑肌细胞中因烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶激活而产生的超氧化物水平。
招募患有子痫前期的孕妇(子痫前期组,n = 33)和未患子痫前期的孕妇(正常组,n = 37),测定活性氧水平(血清二乙酰反应性氧代谢产物[d-ROM])和血流介导的血管舒张功能(FMD)。对人冠状动脉平滑肌细胞或网膜动脉进行等长力记录、超氧化物水平测定、蛋白质免疫印迹分析和免疫组织化学检测。还在无细胞体系中进行了超氧化物清除试验。
子痫前期组孕妇的FMD低于正常组,血清d-ROM值高于正常组。血清d-ROM水平与FMD程度之间、白蛋白血清水平与d-ROM水平之间呈负相关。D-葡萄糖可降低人网膜动脉中利克溴铵诱导的血管舒张,增加人冠状动脉平滑肌细胞中的超氧化物水平和NADPH氧化酶亚基p47phox的募集。人血清白蛋白(0.05至0.5 g/dL)可预防这些改变,但不具有超氧化物清除作用。
孕妇血清白蛋白与氧化应激呈负相关,但与内皮功能呈正相关。人血清白蛋白似乎通过抑制人血管平滑肌中的NADPH氧化酶来降低氧化应激,这表明血清水平可能是某些人类疾病中血管氧化应激的关键决定因素。