玉米须对糖尿病肾病大鼠肾组织和尿液代谢组学研究

Metabolomics study of corn silk on renal tissue and urine of diabetic nephropathy rats

目的运用代谢组学技术探讨玉米须水煎液对糖尿病肾病(diabetic nephropathy,DN)大鼠的作用机制。方法采用高糖高脂饲料喂养,并多次腹腔注射小剂量链脲佐菌素诱导,建立DN大鼠模型。通过测定肾脏脏器指数、空腹血糖、尿微量白蛋白/尿肌酐、血肌酐、尿素氮、甘油三脂、总胆固醇、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇指标含量,并观察肾组织病理变化,初步评价玉米须对DN模型大鼠的干预作用。进一步采用UPLC/Q-TOF-MS技术,结合主成分分析(principal component analysis,PCA)和正交偏最小二乘法-判别分析(orthogonal partial least squares discriminant analysis,OPLS-DA)方法,筛选出肾组织和尿液中潜在生物标志物,通过HMDB、KEGG数据库鉴定后,导入MetaboAnalyst网站进行代谢通路分析。结果玉米须不同剂量组对上述各项指标及肾脏的病理性损伤均有不同程度的改善,说明玉米须对DN具有较好的干预作用。代谢组学分析表明,玉米须可显著回调18种生物标志物,涉及18条代谢通路,主要有苯丙氨酸和酪氨酸的合成、代谢、核黄素代谢、花生四烯酸代谢等。结论玉米须水煎液干预DN的作用机制可能与氨基酸代谢,核黄素代谢,花生四烯酸代谢有关。

Aim To investigate the mechanism of corn silk decoction on diabetic nephropathy(DN)rats using metabolomics technology.Methods DN rat model was established by feeding with high-sugar and high-fat diet,combined with intraperitoneal injection of low dose streptozotocin.Renal organ index,fasting blood glucose,albumin creatinine ratio,serum creatinine,blood urea nitrogen,triglyceride,total cholesterol,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol indexes were measured,and the pathological changes of renal tissues were also observed to evaluate the intervention effect of corn silk on DN model rats.Further,UPLC/Q-TOF-MS technology was used to screen potential biomarkers in renal tissues and urine,combined with principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA).After identification by HMDB and KEGG database,the biomarkers were imported into MetaboAnalyst for metabolic pathway analysis.Results All indexes and pathological damage of kidneys were improved in groups with different doses of corn silk,indicating that corn silk had a good intervention effect on DN.Metabolomic analysis showed that 18 biomarkers could be significantly called back by corn silk,and it involved 18 metabolic pathways mainly including phenylalanine,tyrosine and tryptophan biosynthesis,riboflavin metabolism,arachidonic acid metabolism,and tyrosine metabolism.Conclusions The mechanism of corn silk decoction intervention on DN may be related to amino acid metabolism,riboflavin metabolism,and arachidonic acid metabolism.