真武汤调节Wnt/β-catenin信号通路对糖尿病肾病大鼠肾脏损伤的影响OA

Objective:To investigate the protective effect of Zhenwu Decoction on renal injury in rats with diabetic nephropathy(DN)and its underlying mechanism.Methods:A DN rat model was established by intraperitoneal injection of streptozotocin(STZ).The successfully modeled rats were randomly divided into a model group,an empagliflozin group(10mg/kg empagliflozin suspension by gavage),a Zhenwu decoction group(25.20g/kg Zhenwu decoction by gavage)and a Zhenwu decoction+pathway activator group(25.20g/kg Zhenwu decoction+10mg/kg SKL2001 solution by gavage),and another 15 normal rats served as the con-trol group.Blood glucose levels were measured with a glucometer.Urinary protein over 24 hours,serum creat-inine(SCR),and blood urea nitrogen(BUN)were detected using an automatic biochemical analyzer.Renal histopathological changes were assessed by hematoxylin-eosin(HE)staining,periodic acid-Schiff(PAS)staining,and Masson's trichrome staining.mRNA levels of monocyte chemoattractant protein-1(MCP-1),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and nuclear factor-κB inhibitor α(IκBα)in renal tissue were measured by RT-qPCR.Protein expression levels of components of the Wnt/β-catenin sig-naling pathway were detected by Western blotting.Results:The kidney tissue of the model group rats showed significant pathological injury and increased glycogen deposition.The levels of blood glucose,24-hour urinary protein,SCR(serum creatinine),BUN(blood urea nitrogen),MCP-1(monocyte chemoattractant protein-1),TNF-α(tumor necrosis factor-alpha),IL-1β mRNA,blue collagen deposition,FN(fibronectin),Col I(collagen type I),Wnt4,p-GSK3β(phosphorylated glycogen synthase kinase-3 beta),β-catenin,and α-SMA(alpha-smooth muscle actin)were significantly upregulated compared to the control group(P<0.05),while the level of IκBα mRNA was significantly lower(P<0.05).The empagliflozin,Zhenwu Decoction,and Zhenwu Decoction+pathway activator groups all exhibited alleviated renal pathological injury,with signifi-cantly lower levels of the above parameters and higher IκBα mRNA levels compared with the model group(P<0.05).Compared with the empagliflozin group,the Zhenwu Decoction and Zhenwu Decoction+pathway ac-tivator groups showed further reductions in the above parameters and a greater increase in IκBα mRNA(P<0.05).Compared with the Zhenwu Decoction group,the Zhenwu Decoction+pathway activator group had sig-nificantly higher levels of blood glucose,24-hour urinary protein,SCR,BUN,MCP-1,TNF-α,IL-1β mRNA,collagen deposition area,FN,Col I,Wnt4,p-GSK3β,β-catenin,and α-SMA,and lower IκBα mRNA(P<0.05).Conclusion:Zhenwu Decoction alleviates renal injury,inhibits inflammatory response,improves renal function and renal fibrosis in DN rats,and its mechanism may be related to inhibiting Wnt/β-catenin signaling pathway.