基于代谢组学的甘草及其蜜炙品改善顺铂致大鼠急性肾损伤的作用机制研究  

The mechanisms of Glycyrrhizae Radix et Rhizoma and its honeyprocessed products on improving cisplatin-induced acute kidney injury in rats based on metabolomics

作　　者：孙娜 化敏 杨青[2,3] 王变利 梁瑞雪[2,3] 张新军 杨晓庆[4] 周建永 周倩[2,3,5] SUN Na;HUA Min;YANG Qing;WANG Bian-li;LIANG Rui-xue;ZHANG Xin-jun;YANG Xiao-qing;ZHOU Jian-yong;ZHOU Qian(College of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Shandong Academy of Chinese Medicine,Jinan 250014,China;Modern Research and Development of Aromatherapy in Traditional Chinese Medicine Shandong Engineering Research Center,Jinan 250014,China;Department of Pathology,the First Affiliated Hospital of Shandong First Medical University,Jinan 250014,China;The key Unit for Research of technique and principle of Honey-processing and Carbonizing of SATCM,Jinan 250014,China)

机构地区：[1]山东中医药大学药学院,山东济南250355 [2]山东省中医药研究院,山东济南250014 [3]传统中医芳疗的现代化研究与开发山东省工程研究中心,山东济南250014 [4]山东第一医科大学第一附属医院病理科,山东济南250014 [5]国家中医药管理局中药蜜制和制炭炮制技术与原理重点研究室,山东济南250014

出　　处：《药学学报》2023年第7期1761-1769,共9页Acta Pharmaceutica Sinica

基　　金：山东省自然科学基金重点项目(ZR2020KH021);国家自然科学基金资助项目(81603299).

摘　　要：本研究采用代谢组学技术探究生、炙甘草对急性肾损伤(acute kidney injury,AKI)大鼠改善作用。所有动物实验均经过山东省中医药研究院动物伦理委员会批准(批准号:SDZYY20200101001)。随机将SD大鼠分为对照组、模型组、生甘草组(0.9 g·kg-1)、炙甘草组(0.9 g·kg-1),每组6只。采用单次腹腔注射顺铂(cisplatin,CP)构建急性肾损伤模型,给予生、炙甘草治疗,苏木精-伊红染色(hematoxylin and eosin,HE)、PAS染色评估肾组织病理变化,检测血清中肌酐(creatinine,Cr)、尿素氮(blood urea nitrogen,BUN)和超氧化物歧化酶(superoxidedismutase,SOD)含量。UPLC-Q-TOF/MS进行组织代谢组学研究,筛选生、炙甘草干预的生物标志物,并进行代谢通路进行分析。结果表明,与模型组相比,生、炙甘草可改善肾组织病理变化,降低血清中Cr、BUN含量,升高SOD活性,此外炙甘草还可以显著降低肾脏指数。组织代谢组学分析筛选得到45种与AKI相关的生物标志物,生、炙甘草可以同时回调其中的11种差异代谢物,参与调控甘油磷脂代谢,色氨酸代谢,苯丙氨酸、酪氨酸和色氨酸生物合成和谷胱甘肽代谢,此外生甘草还参与调控甘氨酸、丝氨酸和苏氨酸代谢与嘧啶代谢。综上,生甘草和炙甘草可参与调控不同的代谢通路,通过调节氨基酸、脂质代谢、能量代谢及氧化应激发挥对AKI大鼠的改善作用。This study used metabolomics to explore the improvement effect of raw and honey-processed Glycyrrhizae Radix et Rhizoma on acute kidney injury(AKI)in rats.All animal experiments were approved by the Animal Ethics Committee of Shandong Academy of Chinese Medicine(approval No.:SDZYY20200101001).SD rats were randomly divided into normal group,model group,raw Glycyrrhizae Radix et Rhizoma group(0.9 g·kg-1)and honey-processed Glycyrrhizae Radix et Rhizoma group(0.9 g·kg-1),6 rats in each group.The rats model of acute kidney injury was established by single intraperitoneal injection of cisplatin(CP)and treated with raw and honey-processed Glycyrrhizae Radix et Rhizoma.The pathological changes of renal tissue were evaluated by hematoxylin and eosin(HE)and PAS staining,the contents creatinine(Cr),blood urea nitrogen(BUN)and superoxide dismutase(SOD)in serum were detected.UPLC-Q-TOF/MS was used to study tissue metabolomics to screen the biomarkers affected by raw and honey-processed Glycyrrhizae Radix et Rhizoma and analyz the metabolic pathways.The results showed that compared with the model group,raw and honey-processed Glycyrrhizae Radix et Rhizoma can significantly improve the pathological changes of renal tissue and decrease the content of Cr,BUN and increase the activity of SOD.In addition,honey-processed Glycyrrhizae Radix et Rhizoma can also significantly reduce the kidney index.In tissue samples,45 biomarkers were measured in AKI rats.Raw Glycyrrhizae Radix et Rhizoma and honey-processed Glycyrrhizae Radix et Rhizoma could simultaneously call back 11 differential metabolites,which were involved in the regulation of glycerophospholipid metabolism,tryptophan metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,and glutathione metabolism.In addition,raw Glycyrrhizae Radix et Rhizoma is also involved in the regulation of glycine,serine and threonine metabolism and pyrimidine metabolism.In summary,raw and honey-processed Glycyrrhizae Radix et Rhizoma can participate in the regulation of different metabolic

关 键 词：生甘草 炙甘草 急性肾损伤 代谢组学 作用机制 

分 类 号：R917[医药卫生—药物分析学]