Study on mechanism of Huangxue Yishen Formula improving chronic renal failure based on serum metabolomics
Objective:To evaluate the efficacy of Huangxue Yishen Formula in treating rats with chronic renal failure,and preliminarily reveal its metabolic regulatory mechanism through metabolomics.Methods:SD rats were divided into normal group,model group,positive drug(valsartan)group,Huangxue Yishen Formula low-dose group and high-dose groups.Chronic renal failure rat model was induced by the combination of Adriamycin(ADR)and adenine,the normal group and model group were administered with 0.9%NaCl solution daily,and the drug-treated groups were intragastrically administered with valsartan 8.33 mg/kg/d and Huangxue Yishen Formula 12.5 and 25 g/kg/d respectively for 6 consecutive weeks.During the experiment,general condition of rats was monitored,24h urine protein and renal function indexes were detected and hematoxylin-eosin(H-E)staining was performed to observe the renal pathological changes.Serum metabolic changes were analyzed by Ultra Performance Liquid Chromatography-Linear Ion Trap Quadrupole-Orbitrap-Mass Spectrometer/Mass Spectrometer(UPLC-LTQ-Orbitrap-MS/MS)to investigate the metabolic regulation mechanism of Huangxue Yishen Formula improving chronic renal failure in rats.Results:Compared with the normal group,signs of exhaustion such as body mass loss,mental depression and weakness were appeared in the rats of the model group,and 24h urine protein was significantly increased,serum creatinine(Scr)and blood urea nitrogen(BUN)were significantly increased(P<0.01),while serum albumin(Alb)was significantly decreased(P<0.01).After drug intervention,all indicators were improved to varying degrees(P<0.05,P<0.01).The pathological results showed that renal tubular injury,interstitial fibrosis and glomerular atrophy and sclerosis in the rats of the model group were effectively improved by Huangxue Yishen Formula.44 differential metabolites were identified by metabolomic study,mainly enriched in the metabolic pathways of arginine biosynthesis,glycerophospholipid metabolism,arachidonic acid metabolism and sphingolipid metabolism.Conclusion:Huangxue Yishen Formula can significantly reduce the phenomenon of urinary protein in rats with chronic renal failure,and alleviate renal impairment,and the main effect mechanism involves its regulatory effects on lipid metabolism and inflammatory damage.
NETL
NSTL
万方数据
