驼乳对顺铂诱导小鼠急性肾损伤的预防保护作用  

Protective effect of camel milk on cisplatin induced acute kidney injury in mice

作　　者：李雅菲 郝世奇 明亮[1] 吕浩迪 斯日古楞 吉日木图[1] LI Yafei;HAO Shiqi;MING Liang;LYU Haodi;SI Riguleng;JI Rimutu(Key Laboratory of Dairy Biotechnology and Engineering,Ministry of Education,Inner Mongolia Agricultural University,Hohhot 010018,China;Animal husbandry and fishery workstation in Urad Houqi,Bayan Nur 015500,China)

机构地区：[1]内蒙古农业大学,乳品生物技术与工程教育部重点实验室,内蒙古呼和浩特010018 [2]乌拉特后旗畜牧水产工作站,内蒙古巴彦淖尔015500

出　　处：《食品与发酵工业》2024年第18期16-23,共8页Food and Fermentation Industries

基　　金：国家重点研发计划项目(2020YFE0203300)。

摘　　要：顺铂用于治疗多种癌症,但剂量过高时会在机体内引发急性肾损伤(acute kidney injury,AKI)。为了研究驼乳对顺铂诱导小鼠AKI的预防保护作用及其在Nrf2/HO-1通路中对肾脏的保护机制,该研究建立AKI小鼠模型,检验驼乳的抗氧化、抗炎症和肾保护功能。结果表明,驼乳可显著降低因顺铂诱导而上升的小鼠血尿素氮、血清肌酐、中性粒细胞明胶酶相关载脂蛋白、肾损伤分子-1浓度(P<0.05),可通过清除活性氧降低丙二醛水平(P<0.05),使抗氧化指标超氧化物歧化酶和谷胱甘肽含量上升(P<0.05);驼乳干预亦能显著降低小鼠炎性因子TNF-α、IL-1β、IL-6的含量(P<0.05)。苏木精-伊红染色显示,驼乳可以改善小鼠肾组织切片因顺铂诱导而出现的肾小管扩张、蛋白质沉淀和肾间质有炎性细胞浸润等症状;TUNEL染色结果显示,驼乳干预能改善顺铂导致的细胞凋亡现象。qPCR测定结果表明,驼乳处理显著改善了小鼠肾组织中5个炎症相关基因mRNA表达水平(P<0.05)。驼乳干预可通过增强抗氧化能力来缓解氧化损伤,进而减轻小鼠肾损伤。驼乳还能够抑制肾脏炎症因子的侵入,减少炎症反应,减轻组织病理学损伤与细胞凋亡,这种保护作用可通过调节Nrf2/HO-1通路来实现。Cisplatin is used in the treatment of many types of cancer,but at too high a dose it can cause acute kidney injury(AKI)in the body.To investigate the preventive-protective effect of camel's milk against cisplatin-induced AKI in mice and its renal protective mechanism in the Nrf2/HO-1 pathway,an AKI mouse model was established to test the antioxidant,anti-inflammatory,and renoprotective functions of camel milk.Results showed that camel milk significantly reduced the concentrations of blood urea nitrogen,serum creatinine,neutrophil gelatinase-associated apolipoproteins,and renal injury molecule-1 in mice that were elevated due to the induction of cisplatin(P<0.05),and could reduce malondialdehyde levels by scavenging reactive oxygen species(P<0.05)and increase the content of antioxidant indicators superoxide dismutase and glutathione(P<0.05).Camel milk intervention also significantly reduced the content of inflammatory factors tumour necrosis factor-α,interleukin-1β,and interleukin-6 in mice(P<0.05).HE staining showed that camel milk improved the symptoms of renal tubular dilatation,protein precipitation,and renal interstitium with inflammatory cell infiltration induced by cisplatin in renal tissue sections of mice.TUNEL staining showed that the intervention of camel milk ameliorated the apoptosis phenomenon caused by cisplatin.Real-time fluorescence quantitative PCR(qPCR)measurements of five inflammation-related genes in mouse renal tissues showed that camel milk treatment significantly reduced the expression levels of the above genes(P<0.05).Camel milk intervention mitigates oxidative damage by enhancing antioxidant capacity,which in turn attenuates renal injury in mice.Camel milk also inhibited the invasion of renal inflammatory factors,reduced the inflammatory response,and attenuated histopathological damage and apoptosis,and this protective effect could be achieved by modulating the Nrf2/HO-1 pathway.

关 键 词：急性肾损伤 驼乳 Nrf2/HO-1通路 顺铂 氧化应激 

分 类 号：TS252.1[轻工技术与工程—农产品加工及贮藏工程] R692[轻工技术与工程—食品科学与工程]