Área Farmacología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, CONICET, Rosario, Argentina.
Clin Exp Pharmacol Physiol. 2021 Jul;48(7):987-995. doi: 10.1111/1440-1681.13499. Epub 2021 Apr 8.
Obstructive renal diseases affect renal function and kidney integrity. Nevertheless, little is known about its systemic or extra-renal effects. The organic anion transporting polypeptide 1 (Oatp1) is a carrier expressed in liver and kidneys. In this study, the hepatic and renal expression of Oatp1 was evaluated in rats with obstructive nephropathy. Moreover, the urinary excretion of Oatp1 (Oatp1 ) was evaluated as a potential biomarker for this pathology. Male Wistar rats with bilateral ureteral obstruction for 5 hours (BUO5), 24 hours (BUO24) or sham operated were used. After 24 hours of ureteral releasing, liver and kidney functional parameters, histopathology, Oatp1 tissular expression and Oatp1 were evaluated. For Oatp1 evaluation two groups were added; BUO1 and BUO2 (1 and 2 hours of ureteral obstruction, respectively). Both liver and kidney functional parameters and histopathological studies showed alterations in BUO5 and BUO24. In hepatic homogenates, Oatp1 significantly decreased in BUO groups and in total liver membranes no modifications were observed. In renal homogenates, Oatp1 significantly decreased in BUO groups, but in apical kidney membranes, its expression was increased. Oatp1 was only detected in BUO groups, even in those (BUO1, BUO2) in which no alterations in the traditional parameters of renal function were observed. Modulations in liver and renal expression of Oatp1 could be an organism strategy to attenuate the effects of the disease and an attempt to maintain the complex organ cross-talk between liver and kidneys. Oatp1 could be a new, early and specific biomarker of obstructive nephropathy.
梗阻性肾病影响肾功能和肾脏完整性。然而，人们对其全身或肾脏外的影响知之甚少。有机阴离子转运多肽 1（Oatp1）是一种在肝脏和肾脏中表达的载体。在这项研究中，评估了梗阻性肾病大鼠中 Oatp1 的肝和肾表达。此外，还评估了 Oatp1（Oatp1）的尿排泄作为该病理学的潜在生物标志物。使用双侧输尿管梗阻 5 小时（BUO5）、24 小时（BUO24）或假手术的雄性 Wistar 大鼠。在输尿管释放 24 小时后，评估了肝和肾功能参数、组织病理学、Oatp1 组织表达和 Oatp1。为了评估 Oatp1，还增加了两组；BUO1 和 BUO2（分别为 1 和 2 小时的输尿管梗阻）。BUO5 和 BUO24 均改变了肝和肾功能参数及组织病理学研究。在肝匀浆中，Oatp1 在 BUO 组中显著降低，而在总肝膜中未观察到变化。在肾匀浆中，Oatp1 在 BUO 组中显著降低，但在肾脏顶膜中其表达增加。Oatp1 仅在 BUO 组中检测到，即使在那些（BUO1、BUO2）中观察到肾功能的传统参数没有改变。Oatp1 肝和肾表达的调节可能是机体减轻疾病影响的一种策略，也是试图维持肝脏和肾脏之间复杂的器官交叉对话的一种尝试。Oatp1 可能是梗阻性肾病的一种新的、早期和特异性生物标志物。
