作 者：
朱彦彬;林红英;曾慧;李颖;吴学良;马文澳;陈志宝
关键词：
香叶木素;顺铂;氧化应激;炎症;细胞凋亡;肾损伤
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Bc12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.
译 名：
Mechanism of diosmetin on cisplatin-induced kidney injury in mice
关键词：
diosmetin%cisplatin%oxidative stress%inflammation%apoptosis%nephrotoxicity
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 mod-els,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-ex-posed mRTECs were significantly reduced by diosmetin,and apoptosis-related immunofluorescence showed its significant protective effects against acute kidney injury.At the same time,diosmetin ac-tivated the Nrf2 signaling pathway,including HO-1 and NQO1.In addition,it suppressed the in-flammation-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 su-peroxide 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 Bc12 and 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.
