Attenuating Renal Interstitial Fibrosis by Shenqi Pill via Reducing Inflammation Response Regulated by NF-κB Pathway In Vitro and In Vivo

Abstract

Introduction. One of the most significant clinical features of chronic 
kidney disease is renal interstitial fibrosis (RIF). This study aimed 
to investigate the role and mechanism of Shenqi Pill (SQP) on RIF.
Methods. RIF model was established by conducting unilateral 
ureteral obstruction (UUO) surgery on rat or stimulating human 
kidney-2 (HK-2) cell with transforming growth factor β1 (TGFβ1). 
After modeling, the rats in the SQP low dose group (SQP-L), SQP 
middle dose group (SQP-M) and SQP high dose group (SQP-H) 
were treated with SQP at 1.5, 3 or 6 g/kg/d, and the cells in the 
TGFβ1+SQP-L/M/H were treated with 2.5%, 5%, 10% SQP-containing 
serum. In in vivo assays, serum creatinine (SCr) and blood urea 
nitrogen (BUN) content were measured, kidney histopathology 
was evaluated., and α-smooth muscle actin (α‐SMA) expression 
was detected by immunohistochemistry. Interleukin-1β (IL-1β), 
interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) content, 
inhibitor of kappa B alpha (IKBα) and P65 phosphorylation were 
assessed. Meanwhile, cell viability, inflammatory cytokines content, 
α‐SMA expression, IKBα and P65 phosphorylation were detected 
in vitro experiment. 
Results. SQP exhibited reno-protective effect by decreasing SCr 
and BUN content, improving renal interstitial damage, blunting 
fibronectin (FN) and α‐SMA expression in RIF rats. Similarly, after 
the treatment with SQP-containing serum, viability and α‐SMA 
expression were remarkably decreased in TGFβ1-stimulated HK-2 
cell. Furthermore, SQP markedly down-regulated IL-1β, IL-6, and 
TNF-α content, IKBα and RelA (P65) phosphorylation both in vivo
and in vitro. 
Conclusion. SQP has a reno-protective effect against RIF in vivo
and in vitro, and the effect is partly linked to nuclear factor-kappa 
B (NF-κB) pathway related inflammatory response, which indicates 
that SQP may be a candidate drug for RIF.

DOI: 10.52547/ijkd.7546