The Inhibitory Effect of Salidroside on the Inflammatory Response of Diabetic Nephropathy in Mice Through the CCL2/CCR2 Pathway

AN Na; SHAN Wei; WANG Gang

doi:10.3969/j.issn.2096-305X.2025.02.005

Abstract：Objective To investigate the effect of Salidroside on diabetic nephropathy and explore the specific mechanism of rhodiola rosea glycosides in the treatment of diabetic kidney disease.Methods A diabetic mouse model was established by intraperitoneal injection of streptozotocin,and the mice were administered with salidroside at concentrations of 50,100,and 150μmol/L respectively.The blood glucose levels of the mice in each group were detected at the 4th week,8th week,and 12th week respectively;the contents of 24 hour urinary protein,serum creatinine(Cr),blood urea nitrogen(BUN)and the kidney coefficient were detected by biochemical methods;the levels of beta-2 microglobulin(β2-MG),neutrophil gelatinase-associated lipocalin(NGAL),and kidney injury molecule-1(KIM-1)in urine,as well as the contents of inflammatory factors such as interleukin-10(IL-10),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in renal tissues were detected by enzyme-linked immunosorbent assay(ELISA);the levels of chemokine C-C motif ligand 2(CCL2)and chemokine C-C motif receptor 2 messenger ribonucleic acid(CCR2 mRNA)were detected by real-time quantitative polymerase chain reaction(RT-qPCR);the expressions of IL-10,IL-6,CCL2 and CCR2 related proteins were detected by Western Blot.Results Compared with the CON group,the blood glucose concentration of mice in the DM group increased(P＜0.01);the 24-hour urinary protein increased(P＜0.01);the renal function and kidney coefficient increased(P＜0.01);the levels of β2-MG,NGAL,and KIM-1 increased(P＜0.01);the content and protein level of the IL-10 factor decreased(P＜0.01);the contents and protein levels of TNF-α and IL-6 factors increased(P＜0.01);the mRNA and protein levels of CCL2 and CCR2 increased(P＜0.01).However,after the administration of salidroside in the medium and high-dose groups,the above changes were significantly improved,and there was no obvious change in the low-dose group.On the basis of the intervention in the medium-dose group,the activator GW0742 of CCL2/CCR2 was injected into the caudal vein,which reversed the protective effect of salidroside on the kidneys of diabetic mice.Conclusion Salidroside may inhibit the inflammatory response in the kidneys of diabetic mice through the CCL2/CCR2 pathway,attenuate the renal injury caused by the hyperglycemic environment,and participate in and ameliorate the occurrence and development of diabetic kidney disease.