Transcriptomic and metabolomic analysis of the effects of Zhenwu decoction on kidney yang deficiency pattern in chronic kidney disease

摘要

Objective:To explore the kidney yang deficiency pattern(KYDP)in a chronic kidney disease(CKD)rat model and the mechanisms underlying the effects of Zhenwu decoction(ZWD)by conducting tran-scriptomic and metabolomic analyses.Methods:Adriamycin(ADR)combined with hydrocortisone(HC)was used to induce CKD with KYDP in rats.ADR was injected into the tail vein twice.HC was injected intramuscularly for 8 weeks.ZWD was administered by gavage for 8 weeks.The general condition was observed,24-h urine protein was detected,serum corticosterone,triiodothyronine,thyroxine,TSH,testosterone,cAMP,and cGMP levels were determined,and pathological analysis was conducted.Transcriptomic and metabolomic analyses were conducted to screen differentially expressed genes(DEGs),differentially expressed metabolites(DEMs),and differentially expressed pathways(DEPs).The core DEMs and DEGs were input to Metab-oanalyst 5.0 to identify the pathways affected by ZWD.Results:In the HC group,KYDP symptoms were observed.Compared with control group,the levels of 24-h urine protein,TSH,and cGMP significantly increased(all P<0.01),and corticosterone,triiodothyronine,thyroxine,and cAMP significantly decreased(all P<0.01)in the HC group.After ZWD intervention,the levels of above-mentioned indicators could be reversed to some extent.Pathological analysis in the HC group revealed kidney lesions.DEGs in the ZWD group were mainly associated with pathways such as nucleotide synthesis and endocrine pathways.In the ZWD group,differences in biosynthesis of unsat-urated fatty acids and butanoate metabolism were observed.The following pathways were significantly affected by ZWD:arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.Conclusion:ZWD can be used to treat KYDP in CKD through regulating arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.