Abstract：
Cisplatin (DDP) is widely used in the treatment of cancer as a chemotherapeutic drug. However, its severe nephrotoxicity limits the extensive application of cisplatin, which is characterized by injury and apoptosis of renal tubular epithelial cells. This study aimed to reveal the protective effect and its underlying mechanism of Indole-3-carboxaldehyde (IC) against DDP-induced AKI in mice and NRK-52E cells pretreated with PKA antagonist (H-89). Here, we reported that IC improved renal artery blood flow velocity and renal function related indicators, attenuated renal pathological changes, which were confirmed by the results of HE staining and PASM staining. Meanwhile, IC inhibited the levels of inflammatory factors, oxidative stress, CTR1, OCT2, and the levels of autophagy and apoptosis. Mitochondrial dysfunction was significantly improved as observed by TEM. To clarify the potential mechanism, NRK-52E cells induced by DDP was used and the results proved that H-89 could blocked the improvement with IC effectively in vitro. Our findings showed that IC has the potential to treat cisplatin-induced AKI, and its role in protecting the kidney was closely related to activating PKA, inhibiting autophagy and apoptosis, improving mitochondrial function, which could provide a theoretical basis for the development of new clinical drugs.
摘要：
顺铂(DDP)作为化疗药物广泛用于癌症的治疗。然而,严重的肾毒性限制了顺铂的广泛应用,以肾小管上皮细胞损伤和凋亡为特征。本研究旨在揭示吲哚-3-甲醛（IC）对DDP诱导的小鼠和PKA拮抗剂（H-89）预处理的NRK-52E细胞AKI的保护作用及其机制。这里,据报道，IC改善肾动脉血流速度和肾功能相关指标，肾脏病理变化减弱，HE染色和PASM染色结果证实了这一点。同时,IC抑制炎症因子水平,氧化应激，CTR1、OCT2与自噬和凋亡的水平有关。通过TEM观察到线粒体功能障碍显着改善。为了阐明潜在的机制，使用DDP诱导的NRK-52E细胞，结果证明H-89可以在体外有效阻断IC的改善。我们的研究结果表明，IC具有治疗顺铂诱导的AKI的潜力，其对肾脏的保护作用与激活PKA密切相关,抑制自噬和凋亡，改善线粒体功能，为临床新药的开发提供理论依据。
