Effects of Taohong Siwu Decoction on renal protection and ERK1/2/HIF-1α signaling pathway in rats with mesangial proliferative glomerulonephritis

Objective To explore the therapeutic effect of Taohong Siwu Decoction(ThSwT on mesangial proliferative nephritis(MsPGN) in rats and examine its regulatory effect on extracellular regulated protein kinase 1/2(ERK1/2)/hypoxia inducible factor 1α(HIF-1α) signaling pathway.Methods A total of 72 Sprague-Dawley(SD) rats were randomly divided into six groups of normal control,model,low-dose(4.5 g/kg),medium-dose(9 g/kg),high-dose(18 g/kg) ThSwT and positive control(5 mg/kg of prednisone acetate) (n=12 each). Except for normal control group,another group received a subcutaneous injection of bovine serum albumin(BSA) for establishing a rat model of MsPGN. ThSwTwas delivered via gavage after successful modeling. Each group was dosed once daily for 28 daysand at24 h after the last dose. General behavior changes were observed and 24 h urinary protein was detected;the levels of creatinine(Scr) and blood urea nitrogen(BUN) were detected by enzyme-linked immunosorbent assay and the proliferation of glomerular mesangial area was observed by transmission electron microscope;Periodic acid-leuco fuchsin staining method(PAS) for observing the extracellular matrix proliferation of glomerular mesangial cells;the expressions of immunoglobulin M(IgM) and collagen IV(ColIV) detected by immunofluorescent staining;the expressions of ERK1/2 and HIF-1α by immunohistochemistry;the expressions of ERK1/2,p-ERK1/2,tissue inhibitor of metalloproteinase-1(TIMP-1),matrix metalloproteinase-9(MMP-9),tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) by Western blot.Results Compared with those in normal control group,electronic density deposition of glomerular mesangial area,glomerular epithelial cell foot swelling,glomerular basement membrane thickening and irregular arrangement were serious in model group,24 h urinary protein,Scr,BUN,IgM &Col-IV deposition and positive expressions of ERK1/2,HIF-1α,p-ERK1/2/ERK1/2,MMP-9,TNF-α and IL-6 increased(P<0.05). Compared with those in model group,electronic density deposition of glomerular mesangial area,glomerular epithelial cell foot swelling,glomerular basement membrane thickening and irregular arrangement became alleviated in low/medium/high-dose ThSwT and positive control groups,24 h urinary protein,Scr,BUN,IgM &Col-IV deposition,ERK1/2 &HIF-1α positive expression and protein expressions of p-ERK1/2/ERK1/2,MMP-9,TNF-α and IL-6 declined(P<0.05). With the incremental dose of ThSwT,the above parameters changed more significantly(P<0.05) while no significant difference existed between medium-dose ThSwT and positive control groups(P>0.05).Conclusions ThSwT may inhibit the activation of ERK1/2/HIF-1α pathway,retard the process of renal inflammation and fibrosis and improve the process of renal injury in MsPGN rats.