Effects of a Self-Designed Yiqi Qingre Jiedu Huayu Formula on Membranous Nephropathy and the Wnt1/β-catenin Signaling Pathway
LU Yongxia1*, WANG Ning2, LIU Xiaojiang3
This study aims to investigate the renal protective effects and potential mechanisms of the SDYF (self-designed Yiqi Qingre Jiedu Huayu formula) on membranous nephropathy. In the clinical study, 80 patients with membranous nephropathy were enrolled and randomly divided into a control group and an observation group, with 40 patients in each group. The control group received basic treatment combined with benazepril hydrochloride, and the observation group received SDYF on the basis of the control group’s treatment. Both groups were treated continuously for 6 months. Clinical data were collected from both groups. Renal function parameters [24 h UTP (24-hour urine protein quantification), serum ALB (albumin), BUN (blood urea nitrogen), Scr (serum creatinine)], serum lipid profile [TC (total cholesterol), TG (triglycerides)], and anti-PLA2R (phospholipase A2 receptor) antibody levels were measured before and after treatment in both groups. TCM (traditional Chinese medicine) syndrome scores and clinical efficacy were also compared between the two groups. In the animal study, a rat model of membranous nephropathy was successfully established by the method of injecting CBSA (cationized bovine serum albumin) via the tail vein. Rats with successful modeling were randomly divided into five groups: a normal control group (without modeling or drug administration), a model group, a western medicine group (treated with benazepril hydrochloride at 10 mg/kg), a low-dose SDYF group (administered at 11.65 g/kg), and a high-dose SDYF group (administered at 23.31 g/kg), with 10 rats in each group. After 4 weeks of continuous drug administration, renal function parameters and lipid parameters were determined in each group. Renal tissue pathology was observed through HE (hematoxylin and eosin), Masson staining, and PAS (periodic acid-Schiff) staining. Immunohistochemistry was used to detect the expression levels of α-SMA (α-smooth muscle actin), Col-I (type I collagen), and fibronectin in rat kidney tissue. Immunofluorescence staining was used to observe IgG and C5b-9 deposition. TEM (transmission electron microscopy) was used to observe the podocyte structure. Western blot analysis was performed to detect the expression of podocyte injury-related proteins [WT-1 (Wilms’ tumor protein 1), nephrin, and podocin] as well as Wnt1/β-catenin signaling pathway-related proteins [Wnt1, β-catenin, c-Myc, and MMP-7 (matrix metalloproteinase 7)] in renal tissue. The results showed that after treatment, both groups exhibited significantly reduced levels of 24 h UTP, TC, TG, BUN, Scr, and anti-PLA2R antibody, as well as significantly decreased TCM syndrome scores (P<0.05). Concurrently, ALB levels demonstrated a significant increase (P<0.05). Furthermore, the observation group achieved a higher overall response rate than the control group (P<0.05). In animal experiments, compared with the control group, the rats in the model group exhibited significant pathological damage to the renal tissue, increased deposition of IgG and C5b-9, and aggravated podocyte injury; the levels of 24 h UTP, TC, and TG, as well as the positive expression levels of α-SMA, Col-I, fibronectin, and the expression levels of Wnt1/β-catenin pathway-related proteins in the renal tissue, were significantly elevated (P<0.05). Additionally, serum ALB levels and the expression levels of podocyte injury-related proteins were significantly reduced (P<0.05). Compared with the model group, the renal tissue pathological damage in the western medicine control group, low-dose SDYF group, and high-dose SDYF group was significantly reduced, with decreased deposition of IgG and C5b-9 and reduced podocyte injury; the levels of 24 h UTP, serum TC, and TG, as well as the positive expression levels of α-SMA, Col-I, and fibronectin in the renal tissue, and the expression levels of Wnt1/β-catenin pathway-related proteins, were significantly decreased (P<0.05), while serum ALB levels and the expression levels of podocyte injury-related proteins were significantly increased (P<0.05). Among them, the high-dose SDYF group showed the best improvement. In summary, SDYF alleviates renal injury caused by membranous nephropathy, and its mechanism of action may be related to inhibiting the Wnt1/β-catenin signaling pathway.
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