Dendrobium mixture attenuates renal damage in rats with diabetic nephropathy by inhibiting the PI3K/Akt/mTOR pathway

Dendrobium mixture (DMix) is a Traditional Chinese Medicine widely used for preventing and treating diabetic nephropathy (DN). Autophagy contributes to DN development and progression. The present study aimed to investigate the mechanism underlying the protective effects of DMix on the kidneys of rats with DN and to determine whether this involves autophagy. Herein, a high-sugar and high-fat diet, combined with the intra-abdominal injection of low-dose streptozocin, was used to induce DN in 40 Sprague-Dawley male rats. In total, 10 additional rats were used as controls. The rats with DN were then randomly divided into three groups and treated with DMix, gliquidone or saline via gastric administration for 8 weeks. Body weight, kidney weight, kidney index, fasting blood glucose (FBG), blood lipid, hemoglobin A1c (HbA1c), insulin, blood urea nitrogen and serum creatinine levels, as well as the 24-h urinary albumin excretion rate (UAER) were measured. H&E, Periodic Acid-Schiff and Masson staining were used to examine the renal pathology. The mRNA and protein expression levels of LC3 and Beclin-1 in renal tissues were measured using reverse transcription-quantitative PCR and immunohistochemistry, respectively. Western blotting was conducted to measure the protein expression levels of PI3K, phosphorylated (p)-PI3K, Akt, p-Akt, mTOR, p-mTOR, LC3 and Beclin-1 in renal tissues. It was found that DMix significantly reduced the FBG, blood lipids, HbA1c and insulin levels, kidney weight, kidney index and UAER in rats with DN, as well as improved renal function. Rats with DN showed notable glomerular hypertrophy, an increase in mesangial matrix content and renal interstitial fibrosis. Moreover, DMix notably reduced kidney damage. The results demonstrated that DMix inhibited the phosphorylation of PI3K, Akt and mTOR in the kidney tissues of rats with DN, and increased the protein and mRNA expression levels of LC3 and Beclin-1. Therefore, it was suggested that DMix has protective effects on the kidney of rats with DN, which may be associated with the inhibition of the PI3K/Akt/mTOR signaling pathway and activation of renal autophagy by this traditional medicine.