Reactive oxygen species/oxidative stress contributes to progression of kidney fibrosis following transient ischemic injury in mice
Reactive oxygen species/oxidative stress contributes to progression of kidney fibrosis following transient ischemic injury in mice
复制标题
活性氧/氧化应激导致小鼠短暂缺血损伤后肾脏纤维化恶化
DOI：
10.1152/ajprenal.90735.2008
复制
发表时间：
2009-08-01
影响因子：
4.2
通讯作者：
Park, Kwon Moo
中科院分区：
文献类型：
--
作者：
Kim, Jinu;Seok, Young Mi;Park, Kwon Moo
金J，徐YM，郑K - J，朴KM。活性氧/氧化应激促进小鼠短暂性缺血损伤后肾纤维化的进展。《美国生理学杂志 - 肾脏生理学》297卷：F461 - F470，2009年。首次发表于2009年5月20日；doi:10.1152/ajprenal.90735.2008。 - 近期，移植后的肾纤维化已被认为是慢性移植肾肾病的主要病因。在移植过程中，短暂性缺血是不可避免的事件。活性氧（ROS）在缺血再灌注（I/R）诱导的急性肾损伤以及高血压、糖尿病和输尿管梗阻等多种疾病的纤维化进展中起关键作用。然而，ROS/氧化应激在I/R损伤后的慢性肾纤维化中的作用仍有待明确。在本研究中，我们探讨了ROS/氧化应激在小鼠肾I/R后肾纤维化中的作用。小鼠在第0天接受双侧肾缺血30分钟，随后再灌注，并在I/R后48小时开始，连续14天分别给予四（1 - 甲基 - 4 - 吡啶基）锰（III）卟啉（MnTMPyP，5mg/kg体重，腹腔注射），一种细胞可透性超氧化物歧化酶（SOD）模拟物，或0.9%生理盐水（对照）。I/R显著增加了术后16天肾脏的间质扩展、胶原沉积、肾小管上皮细胞凋亡、硝基酪氨酸表达、过氧化氢产生和脂质过氧化，并降低了铜 - 锌SOD、锰SOD和葡萄糖 - 6 - 磷酸脱氢酶的活性。给予MnTMPyP可使这些缺血后的变化最小化。此外，给予MnTMPyP显著减轻了I/R后α - 平滑肌肌动蛋白、增殖细胞核抗原（PCNA）、S100A4、CD68和热休克蛋白47表达的增加。我们得出结论，肾纤维化在I/R损伤后慢性发展，并且这一过程与ROS/氧化应激的增加有关。
Kim J, Seok YM, Jung K-J, Park KM. Reactive oxygen species/oxidative stress contributes to progression of kidney fibrosis following transient ischemic injury in mice. Am J Physiol Renal Physiol 297: F461-F470, 2009. First published May 20, 2009; doi:10.1152/ajprenal.90735.2008.-Recently, kidney fibrosis following transplantation has become recognized as a main contributor of chronic allograft nephropathy. In transplantation, transient ischemia is an inescapable event. Reactive oxygen species (ROS) play a critical role in ischemia and reperfusion (I/R)-induced acute kidney injury, as well as progression of fibrosis in various diseases such as hypertension, diabetes, and ureteral obstruction. However, a role of ROS/oxidative stress in chronic kidney fibrosis following I/R injury remains to be defined. In this study, we investigated the involvement of ROS/oxidative stress in kidney fibrosis following kidney I/R in mice. Mice were subjected to 30 min of bilateral kidney ischemia followed by reperfusion on day 0 and then administered with either manganese (III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP, 5 mg/kg body wt ip), a cell permeable superoxide dismutase (SOD) mimetic, or 0.9% saline (vehicle) beginning at 48 h after I/R for 14 days. I/R significantly increased interstitial extension, collagen deposition, apoptosis of tubular epithelial cells, nitrotyrosine expression, hydrogen peroxide production, and lipid peroxidation and decreased copper-zinc SOD, manganese SOD, and glucose 6-phosphate dehydrogenase activities in the kidneys 16 days after the procedure. MnTMPyP administration minimized these postischemic changes. In addition, MnTMPyP administration significantly attenuated the increases of alpha-smooth muscle actin, PCNA, S100A4, CD68, and heat shock protein 47 expression following I/R. We concluded that kidney fibrosis develops chronically following I/R injury, and this process is associated with the increase of ROS/oxidative stress.