Abstract
Diabetic nephropathy (DN) is a chronic kidney disease that develops in patients with diabetes mellitus (DM). Renal dysfunction and persistent proteinuria are the main clinical features of DN. Podocyte injury is an important cause of persistent proteinuria and diabetic kidney disease (DKD) progression. Traditional Chinese patent medicines can improve renal function by enhancing autophagy and promoting apoptosis. Keluoxin is a Chinese patent medicine that has the effect of invigorating qi and nourishing yin, activating blood, and eliminating blood stasis. Therefore, we hypothesized that Keluoxin may have a protective effect against diabetic nephropathy in rats with type 2 DM. Rats induced with diabetes through streptozocin (STZ) injection and a high-fat and high-sugar diet were treated with Keluoxin (0.63 g/kg/day) for 8 weeks, and renal function, biochemical indicators, and histopathological changes in renal tissues were observed. Immunofluorescence staining and western blot analysis were used to detect the expression of autophagy-related proteins. The results showed that Keluoxin reduced blood glucose and lipid levels, improved renal function, and alleviated renal histopathological changes in rats with DN. The therapeutic effect was similar to that of Irbesartan (15.6 mg/kg/day). It is inferred that the mechanism works through reducing the obstruction of downstream pathways of autophagy by improving the lysosomal degradation function and alleviating podocyte injury. This study demonstrates that Keluoxin could regulate autophagy in podocytes, alleviate kidney injury in rats with DN, and have a protective effect on renal function; its mechanism can thus be a potential therapy for DN.
Highlights
Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetes mellitus (DM); it has become the main cause of chronic kidney disease (CKD) in developed countries and is an important cause of endstage nephropathy in China [1, 2]. e study found that the prevalence of diabetic kidney disease (DKD) in the Chinese diabetic population is approximately 20–40%, which seriously affects the quality of life of patients [3]. e causes of DN are complicated; a study has shown that podocyte injury is an important cause of proteinuria persistence and DKD progression [4]
Protein 1 light chain 3B (LC3) and p62 are autophagy-related proteins, and studies have shown that persistent high glucose (HG) in DN leads to increased activation of renal epidermal growth factor receptor (EGFR) signals, inhibits autophagy-associated protein expression, and decreases autophagy activity [10, 15]
Keluoxin can alleviate renal histopathological changes and delay DN progression, and it has a protective effect against DN in a model of type 2 DM. is effect may be achieved by regulating autophagy in podocytes; the mechanism may be a potential therapy for DN which needs further investigation
Summary
Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetes mellitus (DM); it has become the main cause of chronic kidney disease (CKD) in developed countries and is an important cause of endstage nephropathy in China [1, 2]. e study found that the prevalence of diabetic kidney disease (DKD) in the Chinese diabetic population is approximately 20–40%, which seriously affects the quality of life of patients [3]. e causes of DN are complicated; a study has shown that podocyte injury is an important cause of proteinuria persistence and DKD progression [4]. E causes of DN are complicated; a study has shown that podocyte injury is an important cause of proteinuria persistence and DKD progression [4]. Recent studies have established that glomerular podocytes are damaged in the early stage of diabetes; podocyte injury is closely related to the occurrence and development of DKD and is the core factor in DKD progression [6]. Autophagy plays a key role in maintaining the structure and function of podocytes, and its excessive activation or inhibition is the cause of podocyte damage [4]. Studies have shown that autophagy imbalance alters podocyte structure and function in patients with DM, and Evidence-Based Complementary and Alternative Medicine impaired autophagy, damaged podocytes, and massive proteinuria were observed in diabetic patients or rats induced with diabetes [10, 11]. Impaired autophagy activity contributes to the pathogenesis of DN. erefore, recovery of autophagy activity may be a promising therapy for DN [16, 17]
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