基于肾毒理论探讨益肾祛风方对阿霉素致小鼠肾损伤的防治作用及肾脏代谢组学研究  

Investigate the preventive and therapeutic effects of Kidney-Tonifying and Wind-Eliminating Prescription on adriamycin-induced kidney injury in mice and its renal metabolomics based on nephrotoxicity theory

作　　者：黄国顺 雍晨 张敏[1,3] 俞涌飞[1,2,3,4] 陈玮 祝一叶 周恩超[1,2,3,4] HUANG Guoshun;YONG Chen;HANG Min;YU Yongfei;CHEN Wei;ZHU Yiye;ZHOU Enchao(Affliated Hospital of Nanjing University of Chinese Medicine(Jiangsu Provincial Hospital of Traditional Chinese Medicine),Nanjing 210029,China;Key Laboratory of Jiangsu Provincial Universities(Nanjing University of Chinese Medicine Key Laboratory of TCM Tonify Kidney Yuan-primordial and Anti-aging Research),Nanjing 210023,China;The First Clinical Medical College of Nanjing University of Chinese Medicine,Nanjing 210046,China;TCM Master ZOU Yanqin's Inheritance Studio,Nanjing 210029,China;Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine(Wuxi Hospital of Traditional Chinese Medicine),Wuxi 210029,China)

机构地区：[1]南京中医药大学附属医院(江苏省中医院),南京210029 [2]南京中医药大学中医补益肾元抗衰老研究江苏省高校重点实验室,南京210023 [3]南京中医药大学第一临床医学院,南京210046 [4]国医大师邹燕勤传承工作室,南京210029 [5]南京中医药大学无锡附属医院(无锡市中医医院),无锡2100291

出　　处：《中华中医药杂志》2024年第9期4938-4945,共8页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：江苏省研究生实践创新计划项目(No.SJCX23_0904);第三批江苏省中医药领军人才项目,江苏省“六大人才高峰”高层次人才项目(No.WSN-012);江苏省科技计划专项资金(重点研发计划社会发展)项目(No.BE2023791);江苏省中医院院级课题面上项目(No.Y22012);无锡市卫生健康委青年科研项目(No.Q202220);南京中医药大学自然科学基金项目(No.XZR2023093);江苏省中医院科技项目(No.Y2022zj07)。

摘　　要：目的:基于肾毒理论探讨益肾祛风方(KWP)对阿霉素致小鼠肾损伤的防治作用及肾脏代谢组学研究。方法:采用单次尾静脉注射阿霉素溶液13.5 mg/kg构建阿霉素致肾损伤动物模型,36只SPF级雄性BALB/c小鼠随机分为空白组、模型组、KWP低剂量组(KWP-L组,26.78 g·kg^(-1)·d^(-1))和KWP高剂量组(KWP-H组,53.56 g·kg^(-1)·d^(-1))。给药干预14 d后,收集血、尿以及肾脏,进行血、尿生化分析以及肾脏病理检测;基于色谱-质谱联用技术(LC-MS)非靶向代谢检测肾脏代谢产物,采用主成分和偏最小二乘判别分析法分析模型组、KWP-H组小鼠肾脏组织代谢产物及其所参与的代谢通路。结果:KWP-H组造模后14 d较模型组小鼠体质量差值显著减少(P<0.01),KWP-L组与KWP-H组较模型组血肌酐、血尿素氮水平以及蛋白尿/肌酐比值均显著降低(P<0.01,P<0.05)。同时,KWP-L组与KWP-H组可以改善肾脏病理,缓解肾脏纤维化。采用LC-MS非靶向代谢组学检测出40个差异代谢产物,富集的通路主要为核苷酸代谢、糖代谢以及脂质过氧化相关代谢途径等代谢通路。结论:KWP可通过干预肾脏组织的代谢产物改善阿霉素致肾损伤。Objective:To investigate the preventive and therapeutic effects of Kidney-Tonifying and Wind-Eliminating Prescription(KWP)on adriamycin-induced kidney injury in mice and its renal metabolomics based on nephrotoxicity theory.Methods:An animal model of renal injury induced by adriamycin was established by a single tail vein injection of adriamycin solution at 13.5 mg/kg.A total of 36 SPF male BALB/c mice were randomly divided into 4 groups:control group,model group,KWP low-dose group(KWP-L group,26.78 g·kg^(-1)·d^(-1))and KWP high-dose group(KWP-H group,53.56 g·kg^(-1)·d^(-1)).After 14 days of intervention,blood,urine and kidney were collected for blood and urine biochemical analysis and renal pathological examination.Kidney metabolites were detected based on non-targeted metabolism by liquid chromatograph-mass spectrometry(LC-MS).Principal component analysis and partial least squares discriminant analysis were used to analyze kidney metabolites and their involved metabolic pathways in model and KPP-H groups.Results:The difference in body mass of mice in KWP-H group was significantly lower than that in model group 14 days after modeling(P<0.01).The blood creatinine,blood urea nitrogen levels and urine protein/creatinine ratio in KWP-L group and KWP-H group were significantly lower than that in model group(P<0.01,P<0.05).At the same time,KWP-L group and KWP-H group can improve renal pathology and relieve renal fibrosis.LC-MS untargeted metabolomics was used to detect 40 differential metabolites,and the enriched pathways were mainly Nucleotide metabolism,glucose metabolism and lipid peroxidation related metabolic pathways.Conclusion:KWP can ameliorate adriamycin-induced renal injury by interfering with renal metabolites.

关 键 词：非靶向代谢组学 益肾祛风方 阿霉素 肾损伤 作用机制 肾毒 肿瘤 癌症 

分 类 号：R285.5[医药卫生—中药学]