Bushen Tongluo recipe improves oxidative stress homeostasis, inhibits transforming growth factor/Notch signaling pathway, and regulates the lncRNA maternally expressed gene 3/miR-145 axis to delay diabetic kidney disease.

Abstract

Objectives: To investigate the effect of Bushen Tongluo recipe (BSTLR, ) on rats with diabetic kidney disease (DKD) and to explore the underlying mechanism of action.

Methods: The rat model of DKD was established, and rats were treated with different doses of BSTLR. Body weight and the levels of urinary protein, α1-microglobulin, glucose, blood urea nitrogen, creatinine, Cystatin C, superoxide dismutase, malondialdehyde, and catalase were analyzed biochemically or by enzyme-linked immunosorbent assay. The pathological damage to renal tissues was assessed by hematoxylin-eosin staining. Immunohistochemical staining was carried out to detect the expression levels of fibronectin, E-cadherin, α-smooth muscle actin, laminin, vimentin, collagen type Ⅳ in kidney tissues. Western blot analysis was conducted to analyze the expression levels of Nephrin, Desmin, Podocin, transforming growth factor-β1, mothers against decapentaplegic homolog 3 (Smad3), Notch1, jagged, hairy and enhancer of split 1 (Hes1) in kidney tissues, and the expression levels of maternally expressed gene 3 (MEG3) and miR-145 were measured by quantitative reverse transcription-polymerase chain reaction. Moreover, dual-luciferase reporter assay was employed to verify the binding of miR-145 to MEG3.

Results: BSTLR increased the body weight of DKD rats, effectively ameliorated the renal function and pathological injury in DKD, regulated the balance of renal oxidative stress, inhibited the TGF/Notch signaling pathway, and affected the variations in the lncRNA MEG3/miR-145 axis.

Conclusion: BSTLR improved oxidative stress homeostasis, inhibited the TGF/Notch signaling pathway, and regulated the lncRNA MEG3/miR-145 axis, effectively delaying the progression of DKD.