Protective Effect and Mechanism of Modified Dahuang Zhechong Wan on Renal Interstitial Fibrosis in Rats with Obstructive Nephropathy / 中国实验方剂学杂志

ABSTRACT

Objective: To explore the protective effect and mechanism of modified Dahuang Zhechong Wan on renal interstitial fibrosis in rats with obstructive nephropathy. Method: The unilateral ureteral ligation (UUO)-induced renal interstitial fibrosis model was adopted, 50 SD rats were randomly divided into 5 groupssham operation group, model group, enalapril group (0.001 g·kg-1), and high and low-dose modified Dahuang Zhechong Wan group (19, 9.5 g·kg-1). Rats in each group were put to death on the 15th day after operation. The serum levels of serum creatinine (SCr) and urea nitrogen (BUN) were collected by enzyme method. The 24-hour urine was collected for 24-hour urinary protein quantity(24 h-Upro) by pyrogallol red molybdenum end point. The kidney tissue was removed from the ligated side. Hematoxylin-eosin (HE) staining and Masson staining were performed; the expressions of transforming growth factor-β1 (TGF-β1), fibronectin (FN) and α-smooth actin (α-SMA) were determined by immunohistochemistry (IHC). Expressions of TGF-β1, p38 mitogen-activated protein kinase (p38 MAPK) and phosphorylated p38 MAPK (p-p38 MAPK) were detected by Western blot. Result: Compared with Sham group, UUO group showed a significant increase in 24 h-Upro, SCr, and BUN (Pβ1, FN, and α-SMA were increased obviously (Pβ1, p38 MAPK, and p-p38 MAPK were increased obviously (PPβ1, FN and α-SMA decreased obviously (Pβ1 and p-p38 decreased obviously (PConclusion: Modified Dahuang Zhechong Wan may improve renal interstitial fibrosis by reducing the high expressions of FN and α-SMA, down-regulating the expressions of p-p38 MAPK and TGF-β1 in p38 MAPK signaling pathway, and decreasing extracellular matrix over deposition and renal cell damage.