探讨益智仁调节脂质代谢对糖尿病肾病小鼠的保护作用

Study on the protective mechanism of Yizhiren regulating lipid metabolism in mice with diabetic nephropathy

目的:应用网络药理学和代谢组学技术探讨益智仁对糖尿病肾病(diabetic nephropathy,DN)小鼠模型的保护机制。方法:检测各组小鼠尿素氮、尿肌酐、尿白蛋白及观察小鼠肾脏病理切片。借助TCMSP数据库与GeneCards数据库分别查找益智仁成分、作用靶点及DN相关基因,构建药物⁃成分⁃靶点⁃疾病网络及KEGG信号通路富集分析。收集益智仁组与生理盐水组小鼠粪便,利用代谢组学技术筛选差异代谢产物,并运用KEGG数据库分析潜在代谢途径。结果:与模型组相比,益智仁显著减轻DN小鼠尿素氮、尿肌酐与尿白蛋白水平(P<0.05或P<0.01),改善小鼠肾脏病理情况。预测益智仁有4种有效成分,且潜在治疗DN的靶点28个。KEGG富集相关信号通路43条,主要代谢途径为脂质代谢。两组粪便共筛选出584个差异代谢物(P<0.05),主要代谢途径为脂质代谢,分别是鞘脂代谢与甘油磷脂代谢,其中包含的代谢产物主要是鞘磷脂、磷脂酰胆碱、溶血磷脂酰胆碱及磷脂酰乙醇胺,且与生理盐水组相比,这4种代谢产物在益智仁组中均显著下降(P<0.01或P<0.001)。结论:益智仁保护糖尿病肾病小鼠的作用机制可能与调节鞘脂代谢、甘油磷脂代谢及其代谢产物紊乱有关。

Objective:To study the protective mechanism of Yizhiren on the diabetic nephropathy(DN)mouse model based on network pharmacology and metabolomics.Methods:Urea nitrogen,urinary creatinine,urinary albumin were detected in each group of mice,and pathological sections of mice kidney were observed.TCMSP database was used to search for the compo⁃nents and targets of Yizhiren,GeneCards database was used to search for DN⁃related genes,and drug⁃component⁃target⁃disease network and KEGG signaling pathway were constructed.The fecal samples of mice in the Yizhiren group and the Saline group were collected,metabolomics techniques were used to screen different metabolites,and potential metabolic pathways were ana⁃lyzed using KEGG database.Results:Compared with the model group,Yizhiren significantly reduced the levels of urea nitrogen,urinary creatinine and urinary albumin in DN mice(P<0.05 or P<0.01),and improved the renal pathology of mice.It was pre⁃dicted that Yizhiren had 4 effective components and 28 potential targets for treating DN.The KEGG enriched 43 signal pathways,and the main metabolic pathway was lipid metabolism.A total of 584 different metabolites were screened from feces of the two groups(P<0.05).The main metabolic pathways were lipid metabolism,namely sphingolipid metabolism and glycerol phospholip⁃id metabolism,among which the metabolites contained mainly sphingolipin,phosphatidylcholine,lysophosphatidylcholine and phosphatidylethanolamine.Compared with the normal saline group,these four metabolites in Yizhiren decreased significantly(P<0.01 or P<0.001).Conclusion:The protective mechanism of Yizhiren in DN mice may be related to the regulation of sphingolipid metabolism,glycerol phospholipid metabolism and the disorder of its metabolites.