Abstract
Background Diabetic nephropathy (DN) is one of the leading causes of end-stage kidney disease. Recently, there is no specific drug available to block the kidney damage. Astragaloside IV (AS-IV) is a major active component of Astragalus membranaceus (Fisch) Bge and has been demonstrated to benefit the kidney functions. This study explores the potential pharmacological action of AS-IV in DN of rats. Methods Male Sprague-Dawley rats were fed with high-fat diet and injected with streptozotocin to induce diabetes. The diabetic rats were randomized and treated with vehicle or AS-IV (80 mg/kg) daily by gavage for 12 weeks as the DN or AS-IV group, respectively. The normal control rats were fed with normal chow and injected with vehicles (n = 8 per group). These rats were monitored for diabetes- and kidney function-related measures. The expression profiles of gene mRNA transcripts in the kidney tissues were analyzed by RNA-seq and quantitative RT-PCR. The levels of advanced glycation end products (AGEs), IL-1β, and IL-18 in the serum samples and kidney tissues were quantified by ELISA. The levels of collagen IV (COL-4) and fibronectin (FN) expression in kidney tissues were examined by immunohistochemistry and Western blot. Results In comparison with the DN group, AS-IV treatment significantly reduced blood glucose levels, food and water consumption, 24 h urine, renal index values, 24 h urine total proteins, blood urea nitrogen (BUN) levels, and creatinine clearance rates (CCR), accompanied by minimizing the DN-induced early kidney damages, fibrosis, and microstructural changes. Furthermore, AS-IV treatment significantly modulated the DN-altered gene transcription profiles in the kidney of rats, particularly for inflammation-related genes, including the nucleotide-binding oligomerization domain-like receptor signaling, which was validated by quantitative RT-PCR. AS-IV treatment significantly decreased the levels of serum and kidney AGEs, IL-1β, and IL-18 expression and fibrosis indexes in the kidney of rats. Conclusion AS-IV treatment ameliorated the severity of DN by inhibiting inflammation-related gene expression in the kidney of rats.
Highlights
Diabetic nephropathy (DN) is one of the most common and primary chronic complications of diabetes and is the most common cause of end-stage kidney disease [1, 2]
We found that the levels of 24-hour urine proteins in DN rats were >30 mg/24 h at least 8-10 weeks post hyperglycemia
The longitudinal measurements indicated that in comparison with that in the normal control (NC) group, the DN group of rats displayed significantly reduced body weights regardless of Astragaloside IV (AS-IV) treatment (p < 0:05 for both) and there was no significant difference in the body weights between the DN and AS-IV groups (Figure 1(a))
Summary
Diabetic nephropathy (DN) is one of the most common and primary chronic complications of diabetes and is the most common cause of end-stage kidney disease [1, 2]. Diabetic nephropathy (DN) is one of the leading causes of end-stage kidney disease. The normal control rats were fed with normal chow and injected with vehicles (n = 8 per group). These rats were monitored for diabetes- and kidney function-related measures. In comparison with the DN group, AS-IV treatment significantly reduced blood glucose levels, food and water consumption, 24 h urine, renal index values, 24 h urine total proteins, blood urea nitrogen (BUN) levels, and creatinine clearance rates (CCR), accompanied by minimizing the DN-induced early kidney damages, fibrosis, and microstructural changes. AS-IV treatment significantly modulated the DN-altered gene transcription profiles in the kidney of rats, for inflammation-related genes, including the nucleotide-binding oligomerization domain-like receptor signaling, which was validated by quantitative RT-PCR. AS-IV treatment ameliorated the severity of DN by inhibiting inflammation-related gene expression in the kidney of rats
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