Effects of Shenkangling intervention on the MAPK pathway in rats with doxorubicin-induced nephropathy.

ABSTRACT

Shenkangling plays a role of Yishenhuoxue effect for the treatment of children with nephrotic syndrome. The aim of this study was to investigate the effects of Shenkangling intervention on the mitogen-activated protein kinase (MAPK) pathway in rats with Adriamycin-induced nephropathy (AN) and its underlying mechanism of action. Nephrosis was induced in healthy Sprague-Dawley rats by doxorubicin and the rats were untreated or treated with prednisone, simvastatin, Shenkangling, or a combination thereof. Using real-time PCR, the mRNA expression levels of Chemokine (C-X-C motif) ligand 16 (CXCL16), A Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), and ADAM17 in the renal tissues of these rats were found to be decreased by the various treatments compared to those in the untreated doxorubicin-induced nephrosis rats. To quantify the activation of the MAPK pathway, western blotting was used to detect the phosphorylation levels of MAPK pathway-associated proteins (p38, ERK1/2, SAPK/JNK) and nuclear factor (NF)-κB p65, which were reduced by the various treatments compared to those in the untreated doxorubicin-induced rats. Serum levels of transforming growth factor (TGF)-ß1, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6, quantified by ELISA, were decreased by the various treatments compared to the levels in the untreated doxorubicin-induced nephrosis rats. The rats treated with prednisone, simvastatin, and Shenkangling showed the best outcome. The Chinese medicine Shenkangling that is known for nourishing the kidney and promoting blood circulation reduced urinary protein levels, increased serum albumin levels, and reduced cholesterol levels by reducing the release of CXCL16, ADAM10, ADAM17, TGF-ß1, TNF-α, IL-1ß, IL- 6, and other inflammatory mediators and inhibiting the activation of the MAPK signaling pathway, thereby effectively improving the state of nephropathy in AN rats. These results indicate that Shenkangling can be used clinically to treat nephropathy.