研究报告

驼乳对顺铂诱导小鼠急性肾损伤的预防保护作用

  • 李雅菲 ,
  • 郝世奇 ,
  • 明亮 ,
  • 吕浩迪 ,
  • 斯日古楞 ,
  • 吉日木图
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  • 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)
第一作者:硕士研究生(吉日木图教授为通信作者,E-mail:yeluotuo1999@vip.163.com)

收稿日期: 2023-09-06

  修回日期: 2023-10-19

  网络出版日期: 2024-10-14

基金资助

国家重点研发计划项目(2020YFE0203300)

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

  • LI Yafei ,
  • HAO Shiqi ,
  • MING Liang ,
  • LYU Haodi ,
  • SI Riguleng ,
  • JI Rimutu
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  • 1(Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot 010018, China)
    2(Animal husbandry and fishery workstation in Urad Houqi, Bayan Nur 015500, China)

Received date: 2023-09-06

  Revised date: 2023-10-19

  Online published: 2024-10-14

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。

本文引用格式

李雅菲 , 郝世奇 , 明亮 , 吕浩迪 , 斯日古楞 , 吉日木图 . 驼乳对顺铂诱导小鼠急性肾损伤的预防保护作用[J]. 食品与发酵工业, 2024 , 50(18) : 16 -23 . DOI: 10.13995/j.cnki.11-1802/ts.037281

Abstract

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.

参考文献

[1] LAMEIRE N, VAN BIESEN W, VANHOLDER R.Acute kidney injury[J].The Lancet, 2008, 372(9653):1863-1865.
[2] 庞浩文, 安宁, 杨陈, 等.Th17细胞及IL-17在急性肾损伤中作用的研究进展[J].临床肾脏病杂志, 2021, 21(11):944-950.
PANG H W, AN N, YANG C, et al.Research advances in functional roles of Th17 and IL-17 in acute kidney injury [J].Journal of Clinical Nephrology, 2021, 21(11):944-950.
[3] HAMED H, GARGOURI M, BOULILA S, et al.Fermented camel milk prevents carbon tetrachloride induced acute injury in kidney of mice[J].The Journal of Dairy Research, 2018, 85(2):251-256.
[4] 于冬冬, 王永欣, 庄语, 等.基于Nrf2-HO-1信号通路的针灸改善顺铂肾损伤小鼠的作用机制研究[J].时珍国医国药, 2022, 33(11):2794-2797.
YU D D, WANG Y X, ZHUANG Y, et al.Mechanism of acupuncture based on Nrf2/HO-1 signaling pathway in improving cisplatin induced renal injury in mice[J].Lishizhen Medicine and Materia Medica Research, 2022, 33(11):2794-2797.
[5] BAKRY I A, YANG L, FARAG M A, et al.A comprehensive review of the composition, nutritional value, and functional properties of camel milk fat[J].Foods, 2021, 10(9):2158.
[6] 蔡树东, 黄浩, 阿里甫·努肉力, 等.骆驼乳对疾病辅助治疗作用研究进展[J].中国草食动物科学, 2019, 39(6):52-55.
CAI S D, HUANG H, ALIFU·N R L, et al.Research progress of camel milk in adjuvant treatment of diseases[J].China Herbivore Science, 2019, 39(6):52-55.
[7] AQIB A I, FAKHAR-E-ALAM KULYAR M, ASHFAQ K, et al.Camel milk insuline:Pathophysiological and molecular repository[J].Trends in Food Science & Technology, 2019, 88:497-504.
[8] JILO K, TEGEGNE D.Chemical composition and medicinal values of camel milk[J].International Journal of Research Studies in Biosciences, 2016, 4(4):13-25.
[9] KORISH A A, ARAFAH M M.Camel milk ameliorates steatohepatitis, insulin resistance and lipid peroxidation in experimental non-alcoholic fatty liver disease[J].BMC Complementary and Alternative Medicine, 2013, 13:264.
[10] ZHU W W, KONG G Q, MA M M, et al.Short communication:Camel milk ameliorates inflammatory responses and oxidative stress and downregulates mitogen-activated protein kinase signaling pathways in lipopolysaccharide-induced acute respiratory distress syndrome in rats[J].Journal of Dairy Science, 2016, 99(1):53-56.
[11] 冯梦雅, 崔莉, 刘健康, 等.骆驼乳的营养价值及在预防疾病中的应用与作用机制研究进展[J].食品科学, 2022, 43(11):392-401.
FENG M Y, CUI LL, LIU J K, et al.Progress in understanding the nutritional value of camel milk and its application and mechanism of action in preventing diseases [J].Food Science, 2022, 43(11):392-401.
[12] ESLAMI O, SHIDFAR F.Dairy products and chronic kidney disease:protective or harmful? A systematic review of prospective cohort studies[J].Nutrition, 2018, 55:21-28.
[13] ZHAO W, LI J, LI Y, et al.Preventive Effect of collagen peptides from Acaudina molpadioides on acute kidney injury through attenuation of oxidative stress and inflammation[J].Oxidative Medicine and Cellular Longevity, 2022, 2022:10.
[14] 刘晓云. 精氨酸对绵羊小肠上皮细胞氧化损伤、凋亡和屏障功能的影响机制研究[D].扬州:扬州大学, 2023.
LIU X Y.Effects of arginine on oxidative injury, apoptosis and barrier function of ovine intestinal epithelial cells[D].Yangzhou:Yangzhou University, 2023.
[15] 马威, 李小全, 王跃玲, 等.NGAL和KIM-1检测对脓毒症所致急性肾损伤的诊断价值[J].湖北民族大学学报(医学版), 2021, 38(3):91-93.
MA W, LI X Q, WANG Y L, et al.Diagnostic value of NGAL and KIM-1 in sepsis induced acute kidney injury[J].Journal of Hubei University (Medical Edition), 2021, 38(3):91-93.
[16] 毕海燕, 刘静, 侯衍豹, 等.肾毒性生物标志物的研究进展及其意义[J].药物评价研究, 2019, 42(1):204-211.
BI H Y, LIU J, HOU Y B, et al.Research progress and significance of biomarkers of nephrotoxicity[J].Drug Evaluation Research, 2019, 42(1):204-211.
[17] PRASAD J R.Acute kidney injury:Diagnosis and management[J].Indian journal of pediatrics, 2020, 87(8):600-607.
[18] ZHANG J, LUAN Z L, HUO X K, et al.Direct targeting of sEH with alisol B alleviated the apoptosis, inflammation, and oxidative stress in cisplatin-induced acute kidney injury[J].International Journal of Biological Sciences, 2023, 19(1):294-310.
[19] MA P, ZHANG S, SU X L, et al.Protective effects of icariin on cisplatin-induced acute renal injury in mice[J].American Journal of Translational Research, 2015, 7(10):2105-2014.
[20] YU C, DONG H, WANG Q, et al.Danshensu attenuates cisplatin-induced nephrotoxicity through activation of Nrf2 pathway and inhibition of NF-κB[J].Biomedicine & Pharmacotherapy, 2021, 142:111995.
[21] 符贻武, 吴志凯, 李佩璇, 等.β-胡萝卜素对脂多糖诱导小鼠急性肾损伤的保护作用及机制[J].中国药学杂志, 2023, 58(4):331-337.
FU Y W, WU Z K, LI P X, et al.Effects and mechanism of β-carotene on LPS-induced acute kidney injury of mice [J].Chinese Pharmaceutical Journal, 2023, 58(4):331-337.
[22] YUAN L, YANG J C, LI Y, et al.Matrine alleviates cisplatin-induced acute kidney injury by inhibiting mitochondrial dysfunction and inflammation via SIRT3/OPA1 pathway[J].Journal of Cellular and Molecular Medicine, 2022, 26(13):3702-3715.
[23] HAMED H, GARGOURI M, BOULILA S, et al.Fermented camel milk prevents carbon tetrachloride induced acute injury in kidney of mice[J].Journal of Dairy Research, 2018, 85(2):251-256.
[24] ARAB H H, EID A H, GAD A M, et al.Inhibition of oxidative stress and apoptosis by camel milk mitigates cyclosporine-induced nephrotoxicity:Targeting Nrf2/HO-1 and AKT/eNOS/NO pathways[J].Food Science & Nutrition, 2021, 9(6):3177-3190.
[25] ARAB H H, ASHOUR A M, ALQARNI A M, et al.Camel milk mitigates cyclosporine-induced renal damage in rats:Targeting p38/ERK/JNK MAPKs, NF-κB, and matrix metalloproteinases[J].Biology, 2021, 10(5):442.
[26] ARAB H H, SALAMA S A, MAGHRABI I A.Camel milk ameliorates 5-fluorouracil-induced renal injury in rats:Targeting MAPKs, NF-κB and PI3K/Akt/eNOS pathways[J].Cellular Physiology and Biochemistry, 2018, 46(4):1628-1642.
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