Molecular Mechanism Of Shen Yan Kang Fu Tablet For Ameliorating Renal Inflammatory Injury In Rat With Adriamycin-induced Nephropathy

[Background/Aims] In this article, the first, we reviewed the progression in the treatment of chronic kidney disease (CKD) with Shen yan kang fu tablet. Shen yan kang fu tablet, a Chinese herbal compound preparation, has the function of invigorating spleen and kidney, clearing dampness-heat, promoting blood circulation for removing blood stasis, and so on. In kidney disease, the clinical trials of Shen yan kang fu tablet in pharmacodynamics are mainly about chronic glomerulonephritis, nephrotic syndrome, IgA nephropathy, diabetic nephropathy, chronic renal insufficiency, and other primary and secondum CKD. It could improve some clinical symptoms, reduce proteinuria and hematuria, ameliorate renal function, and so on. The pharmacological effects of Shen yan kang fu tablet include immunosuppression, anti-inflammation, renal fibrosis amelioration, podocyte and renal tubular epithelial cell protection, etc. The second, we discussed the mechanisms of p38MAPK signaling pathway on renal inflammatory injury in CKD and the interventional effects of Chinese herbal medicine. It is reported, renal inflammation and its relational tissue injury such as glomerularsclerosis and renal interstitial fibrosis play a key role in the progression of CKD to end-stage of renal disease. In which, p38MAPK signaling pathway has a critical function in renal inflammatory injury by controlling many kinds of nuclear factors and their bioactivity, regulating the production of downstream inflammatory mediators, and activating inflammatory cell. The previous studies showed that some Chinese herbs and their extracts, as well as some Chinese herbal prescriptions could ameliorate renal inflammation by regulating p38MAPK signaling pathway. The third, as a focal point in this article, it is reported that the molecular mechanism of Shen yan kang fu tablet for ameliorating renal inflammatory injury in rat with adriamycin-induced nephropathy(ADRN). ADRN model was induced by extirpating one kidney of rats and intravenous injection of adriamycin (ADR) two times. Then, we observed the regulative effects of Shen yan kang fu tablet on p38MAPK signaling pathway, with a purpose to explore the potential molecular mechanisms of Shen yan kang fu tablet for ameliorating renal inflammatory injury through reducing transforming growth factor (TGF)-β1 expression and macrophage infiltration in glomeruli.[Methods] Nineteen Sprague-Dawley (SD) rats were randomly subdivided into 3 groups, the sham-operated group, the vehicle given group, and Shen yan kang fu tablet treated group, and sacrificed at weeks 4 after induction of ADRN induced by 2 consecutive injections of ADR (4 or 2mg-kg-1) with an interval of 2 weeks following unilateral nephrectomy. Daily oral administration of Shen yan kang fu tablet(1.2g·kg-1·d-1) and vehicle as a control was started after the second injection of ADR until the day of sacrifice. Proteinuria and body weight were determined at the end of every week after operation. From blood and kidneys taken at sacrifice, kidney weight, blood biochemical parameters, glomerular morphological changes, podocyte and filter membrane ultrastructure, the infiltration of macrophage ED1+and ED3+, a-smooth muscle actin (a-SMA) and collagen type I were examined, respectively. Furthermore, the protein expressions of TGF-β1 and phosphorylated-p38MAPK(p-p38MAPK)in glomeruli were detected by Western blotting.[Results] Shen yan kang fu tablet not only significantly decreased the infiltration of macrophage ED1+and ED3+, but also markedly down-regulated the protein expressions of TGF-β1 and p-p38MAPK. In addition, it ameliorated proteinuria and serum albumin, but had no effects on blood urea nitrogen (BUN) or serum creatinine (Scr).At the same time, mesangial cell (MC) proliferation, extracellular matrix (ECM), collagen deposition, and the fluorescence stain of a-SMA and collagen type I were attenuated as well.[Conclusion] Shen yan kang fu tablet had effects on ameliorating renal inflammatory injury in vivo by way of intervening the transduction of p38MAPK signaling pathway and improving TGF-β1 expression and macrophage infiltration in glomeruli, through down-regulating the protein expression of the key signal molecule such as p-p38MAPK.