基于蛋白质组学探讨迷迭香酸治疗糖尿病肾病的作用机制OA

Objective To investigate the protective effect of rosmarinic acid(RA)on diabetic nephropathy(DN)and its molecular mechanism.Methods Eighteen db/db mice were used to establish DN models by injection of streptozotocin.After the successful modeling,these mice were randomly divided into model group(Mod group),dapagliflozin group(DAPA group,and RA group.The db/m mice served as control group(Con group).DAPA group received dapagliflozin at a dose of 1.3 mg/(kg·d)by gavage,RA group received RA at a dose of 100 mg/(kg·d)by gavage,while the Con group and Mod group were administered equivalent volume of distilled water by gavage.The administration was performed once daily for 8 weeks.After 8 weeks of intervention,parameters of glucose and lipid metabolism including fasting blood glucose,total cholesterol(TC),triglyceride(TG),high density lipoprotein(HDL)and low density lipoprotein(LDL)were detected;Renal function indexes included serum creatinine(Scr),blood urea nitrogen(BUN),urinary N-acetyl-β-D-glucosaminidase(NAG)and neutrophil gelatinase-associated lipocalin(NGAL)were measured;Masson staining was used to observe renal pathology,and proteomics was used to screen differentially expressed proteins and pathways,and validation was subsequently performed.Results Compared with the Mod group,the RA group had a significant improvement in glucose and lipid metabolism,as shown by a reduction in fasting blood glucose,a reduction in TC,TG,and LDL,and an increase in HDL.Renal function indexes(Scr,BUN,NAG,NGAL)were improved,and renal collagen deposition was decreased.Proteomics analysis showed that ferroptosis pathway was activated in DN model.RA intervention could upregulate the mRNA expression of glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11),downregulate the the mRNA expression of long-chain acyl-CoA synthetase 4(ACSL4),and improve oxidative stress.It was manifested as decreased malondialdehyde(MDA)and increased superoxide dismutase(SOD)activity.Conclusion RA can improve renal injury in DN mice by inhibiting renal ferroptosis.