PDF(Pubmed)
Abstract：
The central exacerbating factor in the pathophysiology of ischemic-reperfusion acute kidney injury (AKI) is oxidative stress. Lipid peroxidation and DNA damage in ischemia are accompanied by the formation of 3-nitrotyrosine, a biomarker for oxidative damage. DNA double-strand breaks (DSBs) may also be a result of postischemic AKI. γH2AX(S139) histone has been identified as a potentially useful biomarker of DNA DSBs. On the other hand, hypoxia-inducible factor (HIF) is the \"master switch\" for hypoxic adaptation in cells and tissues. The aim of this research was to evaluate the influence of hyperbaric oxygen (HBO) preconditioning on antioxidant capacity estimated by FRAP (ferric reducing antioxidant power) and ABTS (2,2\'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assay, as well as on oxidative stress parameter 3-nitrotyrosine, and to assess its effects on γH2AX(S139), HIF-1α, and nuclear factor-κB (NF-κB) expression, in an experimental model of postischemic AKI induced in spontaneously hypertensive rats. The animals were divided randomly into three experimental groups: sham-operated rats (SHAM, n = 6), rats with induced postischemic AKI (AKI, n = 6), and group exposed to HBO preconditioning before AKI induction (AKI + HBO, n = 6). A significant improvement in the estimated glomerular filtration rate, eGFR, in AKI + HBO group (p < 0.05 vs. AKI group) was accompanied with a significant increase in plasma antioxidant capacity estimated by FRAP (p < 0.05 vs. SHAM group) and a reduced immunohistochemical expression of 3-nitrotyrosine and γH2AX(S139). Also, HBO pretreatment significantly increased HIF-1α expression (p < 0.001 vs. AKI group), estimated by Western blot and immunohistochemical analysis in kidney tissue, and decreased immunohistochemical NF-κB renal expression (p < 0.01). Taking all of these results together, we may conclude that HBO preconditioning has beneficial effects on acute kidney injury induced in spontaneously hypertensive rats.
摘要：
在缺血再灌注急性肾损伤（AKI）的病理生理学中，主要的恶化因素是氧化应激。缺血中的脂质过氧化和DNA损伤伴随着3-硝基酪氨酸的形成，氧化损伤的生物标志物。DNA双链断裂(DSB)也可能是缺血后AKI的结果。γH2AX（S139）组蛋白已被鉴定为DNADSB的潜在有用生物标志物。另一方面,缺氧诱导因子（HIF）是细胞和组织缺氧适应的“主开关”。这项研究的目的是评估高压氧（HBO）预处理对FRAP（铁还原抗氧化能力）和ABTS（2,2'-偶氮-双（3-乙基苯并噻唑啉-6-磺酸）测定估计的抗氧化能力的影响，以及氧化应激参数3-硝基酪氨酸，并评估其对γH2AX（S139）的影响，HIF-1α,核因子-κB（NF-κB）的表达，在自发性高血压大鼠诱发缺血后AKI的实验模型中。将动物随机分为三个实验组：假手术大鼠（SHAM，n=6),诱发缺血后AKI的大鼠(AKI，n=6),和在AKI诱导前暴露于HBO预处理的组(AKI+HBO，n=6)。估计的肾小球滤过率显著改善，eGFR,AKI+HBO组（p<0.05vs.AKI组）伴随FRAP估计的血浆抗氧化能力显着增加（p<0.05vs.SHAM组）和3-硝基酪氨酸和γH2AX（S139）的免疫组织化学表达降低。此外，HBO预处理显著增加HIF-1α表达（p<0.001vs.AKI组)，通过Westernblot和免疫组织化学分析在肾组织中估计，免疫组化NF-κB肾组织表达降低(p<0.01)。把所有这些结果放在一起，我们可以得出结论，HBO预处理对自发性高血压大鼠急性肾损伤具有有益作用。
