Department of Anatomy, Physiology, and Biochemistry, Faculty of Medicine, The Hashemite University, Zarqa, Jordan.
Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
PeerJ. 2023 Feb 13;11:e14724. doi: 10.7717/peerj.14724. eCollection 2023.
Acute kidney injury (AKI) is a prevalent medical condition accompanied by mutual affection of other organs, including the liver resulting in complicated multiorgan malfunction. Macrophages play a vital role during tissue injury and healing; they are categorized into "classically activated macrophages" (M1) and "alternatively activated macrophages" (M2). The present study investigated and compared the conventional fluid therapy Dipeptidyl peptidase 4 inhibitor (DPP-4i) vildagliptin on the liver injury induced by AKI and evaluated the possible molecular mechanisms. Thirty rats comprised five groups ( = 6 rats/group): control, AKI, AKI+saline (received 1.5 mL of normal saline subcutaneous injection), AKI+vildagliptin (treated with oral vildagliptin 10 mg/kg), AKI+saline+vildagliptin. AKI was induced by intramuscular (i.m) injection of 50% glycerol (5 ml/kg). At the end of the work, we collected serum and liver samples for measurements of serum creatinine, blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrotic factor-α (TNF-α), and interleukin-10 (IL-10). Liver samples were processed for assessment of inducible nitric oxide synthase (iNOS) as a marker for M1, arginase 1 (Arg-1) as an M2 marker, c-fos, c-Jun, mitogen-activated protein kinase (MAPK), activator protein 1 (AP-1), and high-mobility-group-box1 (HMGB1) protein. The difference was insignificant regarding the relative expression of AP-1, c-Jun, c-fos, MAPK, and HMGB between the AKI+saline group and the AKI+Vildagliptin group. The difference between the same two groups concerning the hepatic content of the M1 marker (iNOS) and the M2 marker Arg-1 was insignificant. However, combined therapy produced more pronounced changes in these markers, as the difference in their relative expression between the AKI+saline+Vildagliptin group and both the AKI+saline group and the AKI+Vildagliptin group was significant. Accordingly, we suggest that the combined saline and vildagliptin hepatoprotective effect involves the downregulation of the MAPK/AP-1 signaling pathway.
急性肾损伤 (AKI) 是一种常见的医学病症，伴有其他器官的相互影响，包括肝脏，导致复杂的多器官功能障碍。巨噬细胞在组织损伤和修复中起着至关重要的作用；它们分为“经典激活的巨噬细胞”（M1）和“替代激活的巨噬细胞”（M2）。本研究调查并比较了传统液体疗法二肽基肽酶 4 抑制剂（DPP-4i）维达格列汀对 AKI 诱导的肝损伤的作用，并评估了可能的分子机制。30 只大鼠分为五组（每组 6 只大鼠）：对照组、AKI 组、AKI+生理盐水组（皮下注射 1.5mL 生理盐水）、AKI+维达格列汀组（口服维达格列汀 10mg/kg）、AKI+生理盐水+维达格列汀组。AKI 通过肌肉内（i.m）注射 50%甘油（5ml/kg）诱导。在工作结束时，我们收集血清和肝组织样本，以测量血清肌酐、血尿素氮（BUN）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、肿瘤坏死因子-α（TNF-α）和白细胞介素-10（IL-10）。处理肝组织样本以评估诱导型一氧化氮合酶（iNOS）作为 M1 的标志物，精氨酸酶 1（Arg-1）作为 M2 的标志物，c-fos、c-Jun、丝裂原活化蛋白激酶（MAPK）、激活蛋白 1（AP-1）和高迁移率族蛋白 1（HMGB1）蛋白。AKI+生理盐水组和 AKI+维达格列汀组之间，AP-1、c-Jun、c-fos、MAPK 和 HMGB1 的相对表达差异无统计学意义。然而，联合治疗在这些标志物上产生了更明显的变化，因为 AKI+生理盐水+维达格列汀组与 AKI+生理盐水组和 AKI+维达格列汀组之间的相对表达差异具有统计学意义。因此，我们认为联合生理盐水和维达格列汀的肝保护作用涉及下调 MAPK/AP-1 信号通路。
