Department of Pharmacy, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Redox Rep. 2009;14(6):243-50. doi: 10.1179/135100009X12525712409896.
Previous studies have reported that selenite, a known antioxidant, protects brain against ischemia/reperfusion injury, which is mediated by oxidative stress. The aim of this study was to investigate whether selenite can protect kidney against ischemic injury by reducing activation of the apoptosis signal regulating kinase 1 (ASK1)/mitogen-activated protein kinase kinase 3 (MKK3)/p38 mitogen-activated protein kinase signaling pathway. The activation and expression of ASK1, MKK3, p38, caspase 3 and cleaved PARP were analyzed by Western blot. Apoptosis of renal tubular epithelial cells was assessed by the terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling method. Malondialdehyde (MDA) levels were measured by the thiobarbituric acid reaction. Blood serum creatinine and blood urea nitrogen level were measured with an Olympus automatic multi-analyzer. We found that selenite attenuated significantly ASK1, MKK3, and p38 phosphorylation at 3 h after renal ischemia. Furthermore, selenite decreased significantly renal epithelial tubular cell apoptosis. In addition, selenite reduced the MDA level. These findings suggest that the protective action of selenite on ischemia renal injury is associated closely with reducing activation of the ASK1-MKK3-p38 signal pathway.
先前的研究表明，亚硒酸盐作为一种已知的抗氧化剂，通过氧化应激途径来保护大脑免受缺血/再灌注损伤。本研究旨在探讨亚硒酸盐是否可以通过减少凋亡信号调节激酶 1（ASK1）/丝裂原活化蛋白激酶激酶 3（MKK3）/p38 丝裂原活化蛋白激酶信号通路的激活来保护肾脏免受缺血性损伤。通过 Western blot 分析 ASK1、MKK3、p38、caspase 3 和裂解的 PARP 的激活和表达。通过末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记法评估肾小管上皮细胞的凋亡。通过硫代巴比妥酸反应测量丙二醛（MDA）水平。使用 Olympus 自动多分析仪测量血清肌酐和血尿素氮水平。我们发现，亚硒酸盐可显著减弱缺血后 3 小时的 ASK1、MKK3 和 p38 的磷酸化。此外，亚硒酸盐可显著减少肾小管上皮细胞凋亡。此外，亚硒酸盐降低了 MDA 水平。这些发现表明，亚硒酸盐对缺血性肾损伤的保护作用与减少 ASK1-MKK3-p38 信号通路的激活密切相关。
