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急性肾损伤的精准医学:黄芩素纳米药物递送系统对抗氧化应激并修复线粒体功能障碍。

Precision medicine for acute kidney injury: Baicalein-nanodrug delivery system combat oxidative stress and repair mitochondrial dysfunction.

作者信息

Zhou Xue, Wang Ning, Zhao Bin, Liu Ziquan, Yu Pei

机构信息

Department of Nephrology, Haihe Hospital, Tianjin University, Tianjin 300350, China; Department of Nephrology, Tianjin Haihe Hospital, Tianjin 300350, China; Haihe Clinical School, Tianjin Medical University, Tianjin 300350, China.

Department of Gastroenterology and Hepatology, Central Hospital, Tianjin University, Tianjin 300170, China; Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China.

出版信息

Int J Pharm. 2025 Jun 10;678:125694. doi: 10.1016/j.ijpharm.2025.125694. Epub 2025 May 6.

Abstract

Acute kidney injury (AKI) is characterized by high morbidity and mortality globally and serves as an independent risk factor for chronic kidney disease. Oxidative stress is the main pathogenic mechanism leading to acute kidney injury (AKI) and subsequent renal failure, which is characterized by excessive reactive oxygen species (ROS) and mitochondrial dysfunction. Treatment options for AKI remain supportive care, it is urgent to develop more viable therapeutic strategies. In this study, we engineered a nanodrug delivery system aiming to achieve precise treatment of AKI. The nanocarriers (Apt-NS) exhibited excellent serum stability and biocompatibility and were capable of specifically recognizing AKI renal tubular cells. Apt-NS were loaded with baicalein (BAI) to form a nanodrug delivery system (Apt-NS-BAI). In comparison to the BAI, Apt-NS-BAI demonstrated more pronounced effects in improving cell viability, scavenging ROS and anti-apoptosis. Simultaneously, in vivo animal experiments also confirmed that Apt-NS-BAI could recognize the injury site and exert biological functions of anti-apoptosis and alleviating renal damage. Overall, this study successfully constructed a nanodrug delivery system with the ability to target AKI renal tubular cells, enabling accurate and efficient delivery of baicalein to injury site and exerting protective functions against oxidative stress. This research offers novel insights into the precision treatment of AKI and contributes to the acceleration of the application of nanotechnology in kidney diseases.

摘要

急性肾损伤(AKI)在全球范围内具有高发病率和死亡率,并作为慢性肾脏病的独立危险因素。氧化应激是导致急性肾损伤(AKI)及随后肾衰竭的主要致病机制,其特征为活性氧(ROS)过量和线粒体功能障碍。急性肾损伤的治疗选择仍然是支持性护理,因此迫切需要开发更可行的治疗策略。在本研究中,我们设计了一种纳米药物递送系统,旨在实现对急性肾损伤的精准治疗。纳米载体(Apt-NS)表现出优异的血清稳定性和生物相容性,并且能够特异性识别急性肾损伤的肾小管细胞。Apt-NS负载黄芩苷(BAI)以形成纳米药物递送系统(Apt-NS-BAI)。与黄芩苷相比,Apt-NS-BAI在提高细胞活力、清除ROS和抗凋亡方面表现出更显著的效果。同时,体内动物实验也证实Apt-NS-BAI能够识别损伤部位并发挥抗凋亡和减轻肾损伤的生物学功能。总体而言,本研究成功构建了一种能够靶向急性肾损伤肾小管细胞的纳米药物递送系统,实现了黄芩苷向损伤部位的精确高效递送,并发挥抗氧化应激的保护作用。本研究为急性肾损伤的精准治疗提供了新的见解,并有助于加速纳米技术在肾脏疾病中的应用。

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