BACKGROUND Ischemia/reperfusion (I/R) injury is a common cause of acute kidney injury (AKI), which occurs clinically during renal organ transplantation and major cardiac surgeries. Previously, it was demonstrated that angiotensin II type 1 receptor (AT1) receptor antagonism is beneficial in the resolution of AKI episodes in young rats by reducing inflammation and oxidative stress. However, studies have shown that aged kidneys are refractory to surgical ischemic pre-conditioning due to increased oxidative stress, mitochondrial dysfunction, inflammation and apoptosis. Therefore, the present study was designed to evaluate the effects of pharmacologically induced pre-conditioning on I/R induced AKI in aged kidneys. METHODS AKI was induced by clamping both renal pedicels for 45 min followed by 24 h of reperfusion. The AT1 receptor antagonist, losartan was administered for three days prior to I/R injury induction in both aged and young rats. Renal outcomes were assessed by serum creatinine, creatinine clearance and proteinuria, renal antioxidant enzyme assays, membrane Na+K+ATPase activity, inflammatory biomarkers, and histological studies. RESULTS AKI developed 24 h post ischemia, as indicated by elevated serum creatinine levels, proteinuria, oxidative stress, reduced membrane Na+K+ATPase activity, increased inflammatory biomarkers levels and histological damage including cellular infiltration, tubular thickening, tubular dilation and necrosis. Losartan pre-treatment significantly improved renal dysfunction and histological alterations in young rats subjected to I/R injury. However, this treatment did not prevent various AKI manifestations in aged rats due to elevated oxidative and inflammatory stress mediated via tubular dysfunction and damage. CONCLUSION We conclude that AT1 receptor antagonism is not beneficial against renal I/R induced AKI in aged rats.

中文翻译：

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衰老通过诱导氧化应激和炎症应激，降低了缺血性肾脏中血管紧张素II 1型受体的拮抗介导的预处理作用。

背景技术缺血/再灌注（I / R）损伤是急性肾损伤（AKI）的常见原因，急性肾损伤（AKI）在临床上发生在肾器官移植和重大心脏手术期间。以前，已证明血管紧张素II 1型受体（AT1）受体拮抗作用通过减少炎症和氧化应激，有助于解决幼年大鼠的AKI发作。然而，研究表明，老年肾脏由于氧化应激增加，线粒体功能障碍，炎症和细胞凋亡而无法进行手术缺血预处理。因此，本研究旨在评估药理学诱导的预处理对I / R诱导的老年肾脏AKI的影响。方法钳住两个肾梗45分钟，然后再灌注24小时，诱发AKI。AT1受体拮抗剂 在诱导I / R损伤之前，在成年和幼年大鼠中都使用了氯沙坦三天。通过血清肌酐，肌酐清除率和蛋白尿，肾脏抗氧化酶测定，膜Na + K + ATPase活性，炎性生物标志物和组织学研究评估肾脏预后。结果AKI在缺血后24小时发展，表现为血清肌酐水平升高，蛋白尿，氧化应激，膜Na + K + ATPase活性降低，炎性生物标志物水平升高和组织学损害，包括细胞浸润，肾小管增厚，肾小管扩张和坏死。氯沙坦预处理可显着改善遭受I / R损伤的幼鼠的肾功能不全和组织学改变。然而，由于肾小管功能障碍和损伤所介导的氧化和炎性应激升高，这种治疗不能预防老年大鼠的各种AKI表现。结论我们得出结论，AT1受体拮抗作用对衰老大鼠的肾脏I / R诱导的AKI无益。