Mechanism of Yishen Xiezhuo Decoction in Treatment of Chronic Renal Failure by Inhibiting NKD2 Activity

  OBJECTIVE  To observe the effect of Yishen Xiezhuo Decoction on various renal function indexes by establishing a mouse model of chronic renal failure (CRF) and explore the mechanism by taking naked stratum corneum homolog 2 (NKD2) as the breakthrough point.

  METHODS  The CRF model of mice was established by unilateral ureteral obstruction (UUO). After the last administration, the mice were killed. The morphology and weight of the mouse kidneys were observed and measured. The renal pathology was observed by Hematoxylin-Eosin and Masson staining. The degree of renal failure was evaluated by renal tubular injury score and renal fibrosis area measurement. Serum IL-1β, IL-6 and TNF-α were determined by enzyme-linked immunosorbent assay (ELISA). The levels of BUN and SCr were detected by kits. Western blot was used to detect the protein expression of Collagen α1, FN1, α-SMA and NKD2.

  RESULTS  Compared with the control group, the kidneys of the model group showed edema, reduced color and enlarged volume; renal mass index, renal tubular injury score, renal fibrosis area and Collagen α1 immunohistochemical expression increased significantly (P < 0.01). Serum levels of BUN, SCr, IL-6, IL-1β and TNF-α were increased significantly (P < 0.01), and the expression of kidney Collagen α1, FN1, α-SMA and NKD2 protein increased, too (P < 0.01). Compared with the model group, no significant difference was found on the scores of renal tubular injury in the low-dose group, but the renal weight index (P < 0.01), the level of renal fibrosis (P < 0.05) and the immunohistochemical expression of Collagen α1 (P < 0.05) decreased significantly. The levels of BUN, SCr, IL-6, IL-1β and TNF-α decreased significantly (P < 0.01), the protein expression of Collagen α1, FN1, α-SMA and NKD2 also decreased significantly (P < 0.01). Compared with the model group, the renal weight index, renal tubular injury scores and renal fibrosis area in the high-dose group were significantly reduced (P < 0.01); The levels of BUN, SCr, IL-6, IL-1β and TNF-α decreased significantly; the protein expression of kidney Collagen α1, FN1, α-SMA and NKD2 decreased significantly, too (P < 0.01).

  CONCLUSION  Yishen Xiezhuo Decoction can down regulate the expression of NKD2, reduce the deposition of renal ECM, inhibit inflammatory responses, and delay the progress of CRF.