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Effects of Shen'an granules on Wnt signaling pathway in mouse models of diabetic nephropathy
Xin-Rong Zou1, Xiao-Qin Wang1, Ying-Lin Hu1
1Department of Nephrology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430061, P.R. China.
Abstract:
The effect of Shen'an granules on the Wnt signaling pathway in renal tissues of mouse models of streptozotocin (STZ)-induced diabetic nephropathy was investigated in the present study. A total of 62 BALB/c mice were randomly divided into the normal control (A group), model (B group), losartan (C group), low-dose Shen'an granules (D group), and high-dose Shen'an granules (E group) groups. The mouse model of diabetic nephropathy was established by a single intraperitoneal injection of STZ (150 mg/kg). The animals were treated with drugs for 8 weeks, and blood creatinine, blood urea nitrogen, triglycerides (TG), and total cholesterol (CHOL) were measured prior to and after treatment. PAS staining was performed for observation of glomerular microstructure by light microscope, and western blot analysis was performed to detect Wnt1 protein and β-catenin protein. The results indicated that the quantification of 24-h microalbuminuria, and levels of blood creatinine, urea nitrogen, TG, and CHOL were significantly lower in the high- and low-dose Shen'an granules groups than those in the model group (p<0.05). The expression levels of Wnt1 protein and β-catenin protein in the high- and low-dose Shen'an granules groups were significantly lower than those in the model group (p<0.05). In conclusion, proteinuria, renal dysfunction, and dyslipidemias are closely associated with the abnormal activation of the Wnt signaling pathway in the mouse model of diabetic nephropathy. The mechanism by which Shen'an granules regulate proteinuria, renal function, and blood lipids may be associated with inhibition of the abnormally activated Wnt signaling pathway.
Insights
Shen'an granules significantly reduced proteinuria, renal dysfunction, and blood lipid levels in a mouse model of diabetic nephropathy. These benefits are linked to the inhibition of the Wnt signaling pathway, a key factor in kidney disease progression.
Area of Science:
- Nephrology
- Pharmacology
- Molecular Biology
Background:
- Diabetic nephropathy is a significant complication of diabetes, characterized by progressive kidney damage.
- The Wnt signaling pathway is implicated in the pathogenesis of diabetic nephropathy, contributing to renal dysfunction and proteinuria.
- Shen'an granules are a traditional Chinese medicine formulation with potential therapeutic effects in kidney diseases.
Purpose of the Study:
- To investigate the effects of Shen'an granules on the Wnt signaling pathway in a mouse model of streptozotocin (STZ)-induced diabetic nephropathy.
- To evaluate the impact of Shen'an granules on renal function, proteinuria, and lipid profiles in this model.
- To elucidate the potential mechanism of action of Shen'an granules in managing diabetic nephropathy.
Main Methods:
- Establishment of a diabetic nephropathy mouse model using streptozotocin (STZ).
- Administration of varying doses of Shen'an granules and losartan for 8 weeks.
- Assessment of renal function markers (creatinine, blood urea nitrogen), lipid profiles (TG, CHOL), and proteinuria (microalbuminuria).
- Histopathological examination of glomerular microstructure using PAS staining.
- Western blot analysis to quantify Wnt1 and β-catenin protein expression.
Main Results:
- Shen'an granules (both low and high doses) significantly reduced 24-h microalbuminuria, blood creatinine, blood urea nitrogen, triglycerides, and total cholesterol compared to the model group (p<0.05).
- The expression of Wnt1 and β-catenin proteins in renal tissues was significantly downregulated in the Shen'an granules groups compared to the model group (p<0.05).
- These findings suggest a protective effect of Shen'an granules against STZ-induced diabetic nephropathy.
Conclusions:
- Abnormal activation of the Wnt signaling pathway is closely associated with proteinuria, renal dysfunction, and dyslipidemias in diabetic nephropathy.
- Shen'an granules demonstrate a therapeutic effect by inhibiting the overactivated Wnt signaling pathway.
- The mechanism underlying the beneficial effects of Shen'an granules on renal function and lipid metabolism may involve the modulation of the Wnt signaling pathway.
