Department of Biochemistry, Faculty of Pharmacy, Deraya University, Minia 61519, Egypt.
Department of Biochemistry, Faculty of Medicine, Assiut University, Assiut 71515, Egypt.
Cells. 2023 Jan 2;12(1):185. doi: 10.3390/cells12010185.
Renal ischemia/reperfusion (IR) injury is characterized by an unexpected impairment of blood flow to the kidney. Azilsartan is an angiotensin receptor blocker that is approved for the management of hypertension. The present study aimed to investigate, on molecular basics, the nephroprotective activity of azilsartan on renal IR injury in rats. Rats were assigned into four groups: (1) Sham group, (2) Azilsartan group, (3) IR group, and (4) IR/Azilsartan-treated group. Histological examination and renal function were evaluated. Levels of KIM-1, HMGB1, caspase 3, GPX, SOD, NF-κB, and p53 proteins were investigated using ELISA. mRNA levels of , , , , , , and were assessed by qRT-PCR. Expression of p38, JNK, and ERK1/2 proteins was investigated by Western blotting. IR injury resulted in tissue damage, elevation of creatinine, BUN, KIM-1, HMGB1, caspase 3, NF-κB, and p53 levels, decreasing GPX and SOD activities, and up-regulation of , , , , , genes. Furthermore, it up-regulated the expression of phosphorylated/total ratio of p38, ERK1/2, and JNK proteins. Interestingly, treatment of the injured rats with azilsartan significantly alleviated IR injury-induced histopathological and biochemical changes. It reduced the creatinine, BUN, KIM-1, HMGB1, caspase-3, NF-κB, and p53 levels, elevated GPX and SOD activities, down-regulated the expression of , , , , , genes, and up-regulated gene expression. Furthermore, it decreased the phosphorylated/total ratio of p38, ERK1/2, and JNK proteins. Azilsartan exhibited nephroprotective activity in IR-injured rats via its antioxidant effect, suppression of inflammation, attenuation of apoptosis, and inhibition of HMGB1/NF-κB/p38/ERK1/2/JNK signaling pathway.
肾缺血/再灌注 (IR) 损伤的特征是肾脏血流意外受损。阿齐沙坦是一种血管紧张素受体阻断剂，已被批准用于治疗高血压。本研究旨在从分子基础上探讨阿齐沙坦对大鼠肾 IR 损伤的肾保护作用。将大鼠分为四组：（1）假手术组，（2）阿齐沙坦组，（3）IR 组，（4）IR/阿齐沙坦治疗组。评估组织学检查和肾功能。采用 ELISA 法检测肾损伤标志物 Kim-1、高迁移率族蛋白 B1（HMGB1）、半胱氨酸天冬氨酸蛋白酶 3（caspase 3）、谷胱甘肽过氧化物酶（GPX）、超氧化物歧化酶（SOD）、核因子-κB（NF-κB）和 p53 蛋白水平。采用 qRT-PCR 法检测 、 、 、 、 、 和 mRNA 水平。采用 Western blot 法检测 p38、JNK 和 ERK1/2 蛋白的表达。IR 损伤导致组织损伤，肌酐、BUN、Kim-1、HMGB1、caspase 3、NF-κB 和 p53 水平升高，GPX 和 SOD 活性降低， 、 、 、 、 、 和 基因上调。此外，它还上调了磷酸化/总比 p38、ERK1/2 和 JNK 蛋白的表达。有趣的是，用阿齐沙坦治疗受伤大鼠可显著减轻 IR 损伤引起的组织病理学和生化变化。它降低了肌酐、BUN、Kim-1、HMGB1、caspase-3、NF-κB 和 p53 水平，提高了 GPX 和 SOD 活性，下调了 、 、 、 、 、 和 基因的表达，上调了 基因的表达。此外，它降低了磷酸化/总比 p38、ERK1/2 和 JNK 蛋白的表达。阿齐沙坦通过抗氧化作用、抑制炎症、减轻细胞凋亡以及抑制 HMGB1/NF-κB/p38/ERK1/2/JNK 信号通路发挥对 IR 损伤大鼠的肾保护作用。
