Abstract
This study was aimed at investigating the synergistical protective effects of Astragalus membranaceus (AG) and Panax notoginseng (NG) on podocyte injury in diabetic rats. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin at 55 mg/kg. Diabetic rats were then orally administrated with losartan, AG, NG, and AG plus NG (2 : 1) for 12 weeks. Albuminuria, biochemical markers, renal histopathology, and podocyte number per glomerulus were measured. Podocyte apoptosis was determined by triple immunofluorescence labeling including TUNEL assay, WT1, and DAPI. Renal expression of nephrin, α-dystroglycan, Bax, Bcl-xl, and Nox4 was evaluated by immunohistochemistry, western blot, and RT-PCR. AG plus NG ameliorated albuminuria, renal histopathology, and podocyte foot process effacement to a greater degree than did AG or NG alone. The number of podocytes per glomerulus, as well as renal expression of nephrin, α-dystroglycan, and Bcl-xl, was decreased, while podocyte apoptosis, as well as renal expression of Bax and Nox4, was increased in diabetic rats. All of these abnormalities were partially restored by AG plus NG to a greater degree than did AG or NG alone. In conclusion, AG and NG synergistically ameliorated diabetic podocyte injury partly through upregulation of nephrin, α-dystroglycan, and Bcl-xl, as well as downregulation of Bax and Nox4. These findings might provide a novel treatment combination for DN.
Highlights
Diabetic nephrology (DN) is one of the most frequent complications of diabetes, and end-stage renal disease (ESRD) in almost 50% of patients was attributed to diabetes in developed countries [1]
No significant differences in the level of serum creatinine (Figure 1(d)) and ALT (Figure 1(e)) were observed between each group, which indicated that Astragalus membranaceus (AG), NG, and AG plus NG did not cause apparent toxicity to the liver and kidney
AG plus NG, rather than AG or NG alone, decreased the kidney weight per body weight ratio in diabetic rats (Figure 1(f)). These results demonstrated that AG and NG synergistically attenuated albuminuria in diabetic rats
Summary
Diabetic nephrology (DN) is one of the most frequent complications of diabetes, and end-stage renal disease (ESRD) in almost 50% of patients was attributed to diabetes in developed countries [1]. Diabetes has become the leading cause of chronic kidney disease in urban Chinese patients since 2011 [2]. Recent studies indicated that podocyte detachment promoted kidney disease in type 2 DN [6]. Our previous study indicated that Astragaloside IV, one of the active components of AG, prevented podocyte apoptosis in vivo and in vitro [13]. Our previous study demonstrated that Notoginsenoside R1, one of the active components of NG, ameliorated podocyte adhesion in vivo and in vitro [15].
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