文献类型：期刊文献

中文题名：香叶木素对顺铂诱导小鼠肾损伤的作用机制

英文题名：Mechanism of diosmetin on cisplatin-induced kidney injury in mice

作者：朱彦彬[1];林红英[1];曾慧[1];李颖[1];吴学良[1];马文澳[1];陈志宝[1]

机构：[1]广东海洋大学滨海农业学院,广东湛江524088

年份：2023

卷号：43

期号：11

起止页码：2336

中文期刊名：中国兽医学报

外文期刊名：Chinese Journal of Veterinary Science

收录：CSTPCD、、CSCD_E2023_2024、北大核心、CSCD、北大核心2020

基金：广东省普通高校重点领域专项资助项目(2020ZDZX1043);广东海洋大学科研启动经费资助项目(R20061)。

语种：中文

中文关键词：香叶木素;顺铂;氧化应激;炎症;细胞凋亡;肾损伤

外文关键词：diosmetin;cisplatin;oxidative stress;inflammation;apoptosis;nephrotoxicity

中文摘要：利用小鼠肾小管上皮细胞(mRTECs)和C57BL/6小鼠建立体外和体内模型,探究香叶木素对顺铂致肾损伤的保护作用。体外试验结果显示,香叶木素能显著降低顺铂诱导的mRTECs细胞内活性氧水平;细胞凋亡结果显示,其对细胞凋亡有明显的抑制作用。同时,香叶木素能激活Nrf2信号通路,提高HO-1和NQO1的表达水平,抑制炎症相关MAPK通路,减少mRTECs的凋亡。通过检测小鼠体内血液中尿素氮(BUN)和血清肌酐(SCr)水平,发现香叶木素可明显缓解顺铂诱导的肾损伤。此外,香叶木素通过提高超氧化物歧化酶(SOD)和谷胱甘肽(GSH)水平,降低丙二醛(MDA)和髓过氧化物酶(MPO)水平,抑制顺铂诱导的氧化应激。肾组织病理组织学分析结果显示,香叶木素能明显减轻顺铂所致的小鼠肾损伤。肾脏组织Western blot结果显示,香叶木素以剂量依赖的方式激活Nrf2通路,通过抑制MAPK信号通路,提升Bcl2的表达及降低Bax的表达,进而抑制细胞凋亡,以保护肾脏免受顺铂诱导的肾损伤。结果提示,香叶木素可能成为防治顺铂诱导肾损伤的一种有效药物。

外文摘要：Cisplatin is a prominent anti-cancer agent,however a series of adverse effects such as nephrotoxicity limits its use.This study aims to determine the protective effects of diosmetin,a natural flavonoid,on cisplatin-induced renal injury and its possible mechanisms.Both mouse renal tubular epithelial cells(mRTECs) and C57BL/6 mice were employed as in vitro and in vivo models,respectively,to examine the protective effects of diosmetin on cisplatin-induced acute kidney injury.In the in vitro experiments,the increased levels of reactive oxygen species in cisplatin-exposed mRTECs were significantly reduced by diosmetin,and apoptosis-related immunofluorescence showed its significant protective effects against acute kidney injury.At the same time,diosmetin activated the Nrf2 signaling pathway,including HO-1 and NQO1.In addition,it suppressed the inflammation-associated MAPK pathway and reduced mRTEC apoptosis.In the in vivo experiments,diosmetin markedly attenuated cisplatin-induced kidney injury.This was revealed by detecting blood urea nitrogen and serum creatinine levels,which represented important indicators of kidney damage.Moreover,cisplatin-induced oxidative stress was inhibited by diosmetin via increasing superoxide dismutase and glutathione levels and decreasing malondialdehyde and myeloperoxidase levels.Furthermore,the histopathological evaluation of kidney tissues showed that diosmetin markedly alleviated cisplatin-induced acute kidney injury.Additionally,the Western blot analysis revealed that diosmetin activated the Nrf2 pathway in a dose-dependent manner,suppressed inflammation via the MAPK signaling pathway,and increase the expression of Bcl2and reduce the expression of Bax,thereby inhibiting apoptosis and protecting the kidney from cisplatin-induced kidney injury.In short,these findings implied that diosmetin might serve as a promising protective agent for cisplatin-induced acute kidney injury.