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华艾多糖通过降低氧化应激和凋亡减轻顺铂肾毒性的作用机制研究。

A polysaccharide from Huaier ameliorates cisplatin nephrotoxicity by decreasing oxidative stress and apoptosis via PI3K/AKT signaling.

机构信息

Department of Urology, Qilu Hospital, Shandong University, Jinan 250012, China.

The second people's Hospital of Huangdao District, Qingdao 266400, China.

出版信息

Int J Biol Macromol. 2019 Oct 15;139:932-943. doi: 10.1016/j.ijbiomac.2019.07.219. Epub 2019 Aug 1.

Abstract

Cisplatin (CP), a common chemotherapy drug used in treatment of malignant tumors. Due to various side effects such as nephrotoxicity (kidney damage), it's efficiency and therapeutic application are limited. This study focuses on finding a suitable drug that would attenuate the side effects like kidney damage, caused by CP. Huaier polysaccharide (HP-1), an extraction of Trametes robiniophila Murr, with a molecular weight of 3 × 10 Da. Previous studies have shown that HP-1, exhibits anti-tumor potential and immunomodulatory effects. We hypothesized that HP-1 has the effect of attenuating the nephrotoxicity caused by CP chemotherapy and protecting renal function. Through our experiments, we observed that HP-1 can attenuate the level of oxidative stress, inflammation and mitochondrial dysfunction, thereby reducing kidney damage. In vitro, we observed that HP-1 significantly inhibits CP-induced renal tubular cell apoptosis and cell cycle arrest. In addition, HP-1 also affects the expression level of the protein by regulating the PI3K/Akt/mTOR signaling pathway and thus attenuates the side effects induced by cisplatin. Therefore, HP-1 may be a potential drug for preventing CP-induced renal damage.

摘要

顺铂(CP)是一种常用于治疗恶性肿瘤的化疗药物。由于其具有肾毒性(肾脏损伤)等各种副作用,其效率和治疗应用受到限制。本研究旨在寻找一种合适的药物,以减轻 CP 引起的肾损伤等副作用。槐耳多糖(HP-1)是从槐栓菌 Trametes robiniophila Murr 中提取的,分子量为 3×10 Da。先前的研究表明,HP-1 具有抗肿瘤潜力和免疫调节作用。我们假设 HP-1 具有减轻 CP 化疗引起的肾毒性和保护肾功能的作用。通过实验,我们观察到 HP-1 可以减轻氧化应激、炎症和线粒体功能障碍的水平,从而减少肾损伤。在体外,我们观察到 HP-1 可显著抑制 CP 诱导的肾小管细胞凋亡和细胞周期阻滞。此外,HP-1 还通过调节 PI3K/Akt/mTOR 信号通路影响蛋白表达水平,从而减轻顺铂引起的副作用。因此,HP-1 可能是预防 CP 引起的肾损伤的一种潜在药物。

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