Danshensu attenuates cisplatin-induced nephrotoxicity through activation of Nrf2 pathway and inhibition of NF-kappa B
Danshensu attenuates cisplatin-induced nephrotoxicity through activation of Nrf2 pathway and inhibition of NF-kappa B
复制标题
丹参素通过激活 Nrf2 通路和抑制 NF-κ B 减轻顺铂诱导的肾毒性
DOI：
10.1016/j.biopha.2021.111995
复制
发表时间：
2021
影响因子：
7.5
通讯作者：
Li Jia-Zhu
中科院分区：
文献类型：
--
作者：
Yu Chen;Dong Hua;Wang Qingchen;Bai Junzhe;Li Yan-Ni;Zhao Juan-Juan;Li Jia-Zhu
顺铂的临床应用主要受到严重的肾毒性的限制。丹参素是从丹参根部提取的主要药理活性二萜类化合物。本研究旨在探讨丹参素对顺铂所致肾毒性的保护作用及其可能机制。禁食12h后，除对照组外，其余各组小鼠均一次性腹腔注射顺铂25 mg/kg。1h后，顺铂(25 mg/kg)+丹参素(15 mg/kg、30 mg/kg、60 mg/kg)组给予相应剂量的丹参素，1次/d，连续7d。测定血尿素氮(BUN)、肌酐(Scr)、活性氧(ROS)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)、过氧化氢酶(CAT)和丙二醛(MDA)。用酶联免疫吸附试验检测炎性细胞因子肿瘤坏死因子-α、白介素6、白介素1β的表达。结果表明，丹参素能改善肾损害，降低血清尿素氮、肌酐、细胞因子和氧化应激指标。进一步研究表明，丹参素可诱导Nrf2/HO-1活化，抑制NF-κB通路。结论：丹参素对顺铂所致肾毒性具有保护作用，其机制可能与激活NRF2/HO-1，抑制NF-ĸB途径有关。
The clinical application of cisplatin was mainly limited by severe nephrotoxicity. Danshensu was the main pharmacological active diterpenoids which extracted from the roots ofSalvia milthiorriza Bunge. This study is aimed to investigate the protective effects and potential mechanisms of Danshensu against cisplatin-induced nephrotoxicity. After fasting for 12 h, all mice groups except the control group were administered a single intraperitoneal injection of 25 mg/kg cisplatin. 1 h later, cisplatin (25 mg/kg) + Danshensu (15 mg/kg, 30 mg/kg, 60 mg/kg) groups were treated with corresponding doses of Danshensu once a day for 7 consecutive days. Blood urea nitrogen (BUN), creatinine, reactive oxygen species (ROS), superoxide dismutase (SOD), Glutathione peroxidase (GPx), Catalase (CAT) and malondialdehyde (MDA) were assayed in this study. The expression of inflammatory cytokines TNF-α, IL-6 and IL-1β were examined by ELISA. The results showed that Danshensu could improve kidney damage, attenuate serum BUN, creatinine, cytokines and oxidative stress markers. Further studies showed that Danshensu can induce Nrf2/HO-1 activation and inhibition of NF-κB pathway. In conclusion, Danshensu exerts the protective effects on cisplatin-induced nephrotoxicity, which may be related to the activation of Nrf2/HO-1 and inhibition of NF-ĸB pathway.