Abstract
Diabetic nephropathy (DN) is a major microvascular complication of diabetes. In addition to moderating hyperglycemia, Shenqi Jiangtang Granule (SJG) had a beneficial effect on kidney function in a clinical trial. However, the mechanism involved remains unclear. This study was conducted to identify the underlying molecular mechanisms. A diabetic rat model was generated by using a high-fat diet and streptozotocin (STZ) injection. Then, rats were given SJG at dosages of 400 mg/kg/d or 800 mg/kg/d by gavage for 8 weeks. After 8 weeks of treatment, blood glucose, serum creatinine, blood urea nitrogen (BUN), and 24-h urinary albumin were measured. Histochemical staining and TdT-mediated dUTP nick-end labeling (TUNEL) assays were performed in kidney. Kidney genomic expression in the SJG-treated group and diabetic group was detected by using a genome expression microarray. We found that SJG treatment reduced blood glucose, serum creatinine, BUN, and 24-h urinary albumin and affected kidney histology. The gene array revealed that the expression of 99 genes increased and the expression of 91 genes decreased in the HSJG group, compared with those of in the diabetic group. Pathway and gene ontology analysis of the differentially expressed genes showed an enrichment of the apoptosis pathway. SJG treatment reduced TUNEL- and caspase-3-positive cells in diabetic kidneys. SJG upregulated Bcl-2 and regucalcin expressions and reduced casp3 and Apaf1 expressions in diabetic rats. Our results suggest that SJG exerts a renal protective effect through the inhibition of cell apoptosis in a diabetic rodent model.
Highlights
E pathological character of diabetic nephropathy (DN) includes abnormal accumulation of extracellular matrix (ECM), thickening and hypertrophy of the glomerular basement membrane, and loss of glomerular and tubular cells, which leads to kidney fibrosis [4]. ese structural changes cause increased proteinuria and albumin excretion and reduced glomerular filtration rate (GFR)
Numerous pathways contribute to the development of DN, including oxidative stress [5], proinflammatory molecules [6], enhanced reactive oxygen species (ROS) [7], activation of protein kinase C [8], increased formation of advanced glycation end products (AGEs) [9], and the renin-angiotensin system (RAS)
A meta-analysis showed that Shenqi Jiangtang Granule (SJG) combination therapy has a better effect than traditional therapy alone, including reducing urinary albumin excretion rate (UAER), serum blood urea nitrogen (BUN), serum creatinine, and 24 h urea albumin in diabetic patients [11]. e mechanism driving this may be involved in inducing HIF-1α and HO-1 expression [12]
Summary
1. Introduction e number of patients with diabetes is dramatically increasing worldwide [1]. DN is a major cause of morbidity and mortality in patients with kidney disease worldwide. A clinical trial indicates that single drug treatment with SJG has an antidiabetic effect in type 2 diabetic patients, compared with that of exercise or dietary intervention [10]. A meta-analysis showed that SJG combination therapy has a better effect than traditional therapy alone, including reducing urinary albumin excretion rate (UAER), serum blood urea nitrogen (BUN), serum creatinine, and 24 h urea albumin in diabetic patients [11]. The exact mechanism underlying the beneficial effect of SJG on kidney function is still unknown. We hypothesized that SJG has multiple targets in the kidney, moderating the kidney fibrosis in diabetic rats.
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