顺铂致急性肾损伤肾脏糖酵解和氨基酸代谢改变的研究  

Changes in renal cell glycolysis and amino acid metabolism during cisplatin-induced acute kidney injury

作　　者：徐申 梁楠楠 任亚辉 何奕樟 张涛[1] 于德新[1] Xu Shen;Liang Nannan;Ren Yahui;He Yizhang;Zhang Tao;Yu Dexin(Dept of Urology,The Second Affiliated Hospital of Anhui Medical University,Hefei 230601;School of Public Health,Anhui Medical University,Hefei 230032)

机构地区：[1]安徽医科大学第二附属医院泌尿外科,合肥230601 [2]安徽医科大学公共卫生学院,合肥230032

出　　处：《安徽医科大学学报》2024年第5期747-752,760,共7页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:82204493);安徽省自然科学基金(编号:2208085QH237)。

摘　　要：目的评估顺铂急性肾损伤过程中肾细胞能量代谢变化。方法成年CD-1雄性小鼠经腹腔注射给予单剂量顺铂(20 mg/kg),检测肾功能和肾组织病理学;转录组分析顺铂对人肾小管上皮细胞基因表达的调控作用并富集通路;LC-MS/MS检测肾脏糖酵解和氨基酸代谢物含量。结果处理组小鼠血清尿素氮和肌酐水平明显上升;病理组织学观察到肾小管上皮细胞发生肿胀和脱落;转录组分析显示顺铂处理72 h引起HK-2细胞2632个基因上调和2799个基因下调;GO和KEGG分析显示差异基因富集于肾细胞能量代谢。GSEA分析结果显示:顺铂处理引起HK-2细胞氧化磷酸化通路上调、糖酵解通路下调;KEGG分析结果显示:顺铂处理引起HK-2细胞氨基酸基因表达改变。代谢组结果显示:顺铂处理72 h导致小鼠肾脏糖酵解中间产物和多种氨基酸含量升高。结论顺铂急性肾损伤过程中伴随肾细胞糖酵解和氨基酸代谢变化。Objective To evaluate the change of energy metabolism during cisplatin-induced acute kidney injury.Methods Adult CD-1 male mice were intraperitoneally injected with a single dose of cisplatin(20 mg/kg),and renal function and renal tissue pathology were tested;gene expression was analyzed and signaling pathways were enriched in cisplatin-treated renal tubular epithelial cells using transcriptome;the contents of renal glycolysis and amino acid metabolites were analyzed using liquid chromatography-tandem mass spectrometry(LC-MS/MS).Results Serum urea nitrogen and blood creatinine significantly increased in cisplatin-treated mice.Pathological histology observed swelling and shedding of renal tubular epithelial cells.Transcriptome analysis revealed that 2632 genes were upregulated and 2799 genes were downregulated in cisplatin-treated HK-2 cells.GO and KEGG analysis showed that differential genes were enriched in energy metabolism.The GSEA analysis results showed that cisplatin caused an upregulation of the oxidative phosphorylation pathway and a downregulation of the glycolysis pathway in renal tubular epithelial cells,further KEGG analysis demonstrated that cisplatin caused changes in the expression of amino acid genes in renal cells.Metabolomics showed that the contents of glycolytic intermediates and several amino acids were altered in the kidney of cisplatin-treated mice.Conclusion Cisplatin-induced acute renal injury is accompanied by modification in renal tubular cell glycolysis and amino acid metabolism.

关 键 词：顺铂 急性肾损伤 细胞代谢 糖酵解 氨基酸代谢 

分 类 号：R692.6[医药卫生—泌尿科学]