Study on the renal protective mechanism of Micromeria biflora (Buch. -Ham. exD. Don) Benth. in focal segmental glomerulosclerosis rats based on the Wnt/DKK1 signaling pathway

Investigating the mechanism by which Micromeria biflora (Buch.-Ham.exD.Don) Benth. inhibits renal injury in rats with focal segmental glomerulosclerosis (FSGS) by regulating the Wnt/Dickkopf-1 (DKK1) signaling pathway.

Sixty male SD rats were classified by body weight into a normal group (n=10) and a modeling group (n=50). The modeling group underwent left nephrectomy followed by two tail vein injections of doxorubicin (3 mg/kg) to establish the FSGS model. Following successful modeling, rats were randomly assigned using a random number table to the model group, prednisolone group, and low-dose Micromeria biflora (Buch.-Ham.exD.Don) Benth.groups, medium-dose Micromeria biflora (Buch. -Ham. exD. Don) Benth. groups, high-dose Micromeria biflora (Buch.-Ham.exD.Don) Benth.groups, with 10 rats per group. The prednisolone group (7.5 mg/kg), Micromeria biflora (Buch. -Ham. exD. Don) Benth. group (150 mg/kg), medium-dose group (300 mg/kg), and high-dose group (450 mg/kg) received corresponding concentrations of the drug via oral gavage. The normal group and model group received an equal volume of ultrapure water via oral gavage, once daily for 6 consecutive weeks. The following parameters were measured using an automated biochemical analyzer after treatment: 24 hour urinary protein (24 h-UP), urinary protein/creatinine ratio (UACR), serum creatinine (SCR), blood urea nitrogen (BUN), albumin (ALB), total cholesterol (CHOL), and triglycerides (TG). Serum interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and transforming growth factor-β1 (TGF-β1) were measured by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescent PCR and Western blotting for renal tissue expression of DKK1, Wingless-type MMTV integration site family member 3A (Wnt3a), β-catenin, and glycogen synthase kinase (GSK3β).

Compared with the normal group, rats in the model group exhibited elevated levels of 24 h-UP, UACR, serum SCR, BUN, CHOL, TG, IL-6, MCP-1, and TGF-β1 (P < 0.05), decreased ALB (P < 0.05), and increased expression of DKK1, Wnt3a, β-catenin, GSK3β mRNA and protein expression in renal tissue also increased (P < 0.05). Compared with the model group, rats in the prednisolone group and low-, medium-, and high-dose Micromeria biflora (Buch. -Ham. exD. Don) Benth. groups showed decreased 24h-UP, UACR, serum SCR, BUN, CHOL, TG, IL-6, MCP-1, TGF-β1 (P < 0.05), and increased ALB (P < 0.05). Renal tissue expression of DKK1, Wnt3a, β-catenin, and GSK3β mRNA and proteins was reduced (P < 0.05).

Micromeria biflora (Buch. -Ham. exD. Don) Benth. may improve FSGS kidney injury by suppressing excessive activation of the Wnt/DKK1 signaling pathway, thereby reducing inflammatory responses and podocyte damage.