吡哆醇缓解顺铂诱导急性肾毒性的作用及机制  

Effect and Mechanism of Pyridoxine in Alleviating Cisplatin-induced Acute Nephrotoxicity

作　　者：唐冰冰 王海畅 洪玲 王佳佳 翁勤洁 TANG Bingbing;WANG Haichang;HONG Ling;WANG Jiajia;WENG Qinjie(College of Pharmaceutical Sciences,Center for Drug Safety Evaluation and Research,Zhejiang University,Hangzhou 310058,China)

机构地区：[1]浙江大学药学院,药物安全评价研究中心,杭州310058

出　　处：《中国现代应用药学》2024年第1期1-8,共8页Chinese Journal of Modern Applied Pharmacy

摘　　要：目的探究吡哆醇是否能够缓解顺铂诱导的急性肾损伤并分析其具体作用机制。方法建立顺铂诱导的HK-2细胞损伤的体外模型后,给予不同浓度的吡哆醇,利用SRB检测细胞存活率,Western blotting检测细胞凋亡和抗氧化蛋白表达,试剂盒检测活性氧分子(reactive oxygen species,ROS)和超氧化物歧化酶(superoxide dismutase,SOD)的含量。进一步建立顺铂诱导的体内肾损伤小鼠模型,给予40 mg·kg^(–1)吡哆醇治疗后检测血清尿素氮水平,分析肾组织的苏木素-伊红染色结果,通过Western blotting检测NRF2的表达。结果吡哆醇在HK-2细胞和小鼠体内均具有保护顺铂诱导的急性肾损伤的作用,在HK-2细胞中吡哆醇下调了ROS水平、上调了SOD酶活力、促进了NRF2及其下游抗氧化相关基因HO-1的表达;在肾损伤小鼠体内,吡哆醇显著降低血清尿素氮水平、修复肾脏组织损伤、上调NRF2表达。结论吡哆醇通过抗氧化应激作用保护了顺铂诱导的急性肾损伤。OBJECTIVE To explore whether pyridoxine can protect acute kidney injury caused by cisplatin and to analyze its specific mechanism.METHODS After establishing an in vitro model of cisplatin-induced damage in HK-2 cells,different concentrations of pyridoxine were administered and cell survival was detected using SRB,the expression of apoptosis-related and antioxidant proteins were detected by Western blotting,and the activity of reactive oxygen species(ROS) and superoxide dismutase(SOD) were detected by kits.A cisplatin-induced mouse kidney injury model was further established,and the serum urea nitrogen level was detected after the administration of 40 mg·kg^(–1) pyridoxine treatment,the results of hematoxylin-eosin staining in renal tissue were analyzed,and the expression of NRF2 was detected by Western blotting.RESULTS Pyridoxine could protect kidney injury caused by cisplatin in HK-2 cells and mouse in vivo.In HK-2 cells,pyridoxine down-regulated ROS level,upregulated SOD enzyme activity,and up-regulated the expression of NRF2 and its downstream antioxidant-related gene HO-1.Pyridoxine significantly reduced the level of serum urea nitrogen,repaired kidney tissue damage,and up-regulated the expression of NRF2 in kidney injury mice.CONCLUSION Pyridoxine protects against cisplatin-induced kidney injury through enhancing the level of anti-oxidative stress.

关 键 词：吡哆醇 顺铂 急性肾脏损伤 氧化应激 

分 类 号：R965.1[医药卫生—药理学]