Effects of Ziyin Qianyang Formula on Renal Fibrosis through the TGF-1/Smads Signaling Pathway in Spontaneously Hypertensive Rats.

OBJECTIVE

The aim of the study is to explore the effects and mechanisms of action of Ziyin Qianyang Formula (ZYQYF) on renal fibrosis in spontaneously hypertensive rats (SHRs).

METHODS

Forty SHRs were randomly divided into a model group, Ziyin Qianyang Formula regular-dose and high-dose groups (ZYQYF-R, 20 g/kg; ZYQYF-H, 40 g/kg), and a western medicine group (enalapril 10 mg/kg), and 10 Sprague-Dawley rats were selected as the normal group. The rats received continuous gavage administration for 6 weeks and systolic blood pressure (SBP) measurements were obtained every fortnight. The serum levels of urea, serum creatinine (sCr), and uric acid (UA) were measured; the pathological morphology and collagen content of the kidneys were observed by hematoxylin-eosin (HE) and Masson staining; and the serum Ang II level was measured by an enzyme-linked immunosorbent assay (ELISA). Transforming growth factor (TGF)-1, Smad-2, Smad-3, and Smad-7 protein and mRNA expressions in kidney tissues was evaluated by western blotting and reverse transcription-polymerase chain reaction.

RESULTS

The ZYQYF-H group showed significantly a lower renal weight and renal weight/body weight than the model group. The enalapril and ZYQYF-H groups showed significantly lower SBP than other groups after 6 weeks of administration. The ZYQYF-H group showed better improvement than the ZYQYF-R and enalapril groups in glomerular and tubular morphology and better reductions in inflammatory cell infiltration and collagen volumetric fraction. The ZYQYF-H group also showed better reductions in serum UA and Ang II levels; collagen-I, collagen-III, and p-Smad2/Smad-2 protein expression; and Smad-2 mRNA expression and a better increase in Smad-7 protein and mRNA expression than the enalapril group. Besides, the degree of renal function and fibrosis improvement was positively correlated with the dose of ZYQYF.

CONCLUSION

ZYQYF can significantly reduce SHR blood pressure, protect renal function and structure, and improve renal fibrosis by regulating Smad proteins through TGF-1.