Exploring the therapeutic potential of Danggui Shaoyao San in nephrotic syndrome: Impact on skin sodium content and renal function

The purpose of this study was to explore the mechanism of sodium transport in the skin of rats with nephrotic syndrome (NS) and the intervention effect of Danggui Shaoyao San (DSS). NS model was established by tail vein injection of adriamycin (ADR), and different doses of DSS, vascular endothelial growth factor receptor-3 (VEGFR-3) inhibitor Levatinib and diuretic amiloride were given for intervention. We analysed serum biochemical parameters, urine sodium, skin sodium and glycosaminoglycan (GAG), lymphatic vessel density, and the expression and mRNA levels of key proteins involved in lymphangiogenesis. The results showed that DSS treatment not only significantly reduced the content of sodium ions in the skin of NS rats, but also effectively alleviated the pathological damage of the kidney, improved proteinuria and promoted the excretion of sodium in urine. At the same time, Levatinib can reduce the content of sodium ions in the skin of NS rats by inhibiting lymphangiogenesis, while amiloride can improve the state of sodium retention in the body and reduce the level of sodium ions in the skin by promoting the excretion of sodium ions in the urine of NS rats. Especially important, DSS can effectively inhibit the proliferation of renal cortical lymphatic vessels, down-regulate the expression of lymphangiogenesis related proteins and mRNA, promote urinary sodium excretion, and inhibit the transport of sodium ions from kidney to skin. In summary, this study reveals that during sodium retention in NS rats, sodium ions can be further transported to the skin for storage through increased lymph in the kidney, and DSS can inhibit renal lymphangiogenesis, promote urinary sodium excretion, and reduce the content of sodium ions in the skin, which provides a novel and potential strategy for the treatment of NS edema.