Danggui Shaoyao San Ameliorates Renal Fibrosis via Regulation of Hypoxia and Autophagy.

Meng-Yun Zhang,Ling-Ling Zhu,Jing Tian,Hui-Juan Chen,Pei Zhao,Ting Zhang,Hui-Hua Chen

doi:10.1155/2019/2985270

Abstract

Danggui Shaoyao San (DSS), a traditional Chinese medicinal prescription, was widely used to reinforce earth to activate collaterals in ancient times. Recently, many clinical studies found that DSS had a renoprotection. In this study, we evaluated the effect of DSS on unilateral ureteral obstruction- (UUO-) induced renal fibrosis in rats and investigated the mechanisms underlying the effect. Sprague Dawley (SD) rats were randomized to UUO or Sham operation. After 1 day, the rats that underwent UUO were randomized to treatment for four experimental groups (n=10 each group): Sham, UUO only, UUO+ benazepril (Bena), and UUO+DSS. After 4 weeks, we demonstrated that DSS significantly suppressed UUO-induced renal hypertrophy by gravimetric. In addition, DSS obviously prevented UUO-induced disorder in renal structure and renal function by HE and biochemistry test. We also found that DSS abrogated UUO-induced renal fibrosis by Masson's staining and collagen volume fraction (CVF) analysis; this is consistent with the western blot analysis that showed DSS abrogated the UUO-induced enhanced TGF-β1 and weakened BMP-7. Compared with the UUO only group, rats treated with DSS exhibited significant increase in vascular density, followed by decrease in hypoxia and HIF-1α protein level through western blot and immunofluorescence analysis. Furthermore, we also determined proteins of autophagy and DSS enhanced autophagy to prevent the damage-induced by UUO. Taken together, our findings demonstrated that DSS had a renoprotection effect in ameliorating renal fibrosis possibly via attenuating tissue hypoxia and regulating autophagy.

Highlights

Chronic kidney disease (CKD) is characterized by abnormalities of kidney structure or function, and the prevalence of CKD is rising greatly in recent years and it has become a worldwide heath issue [1]
Renal fibrosis is regarded as the final common pathway in all forms of CKD and its pathological features include accumulation of extracellular matrix (ECM) as well as extension or atrophy of renal tubule [14]
An approved treatment targeted to renal fibrosis is almost nonexistent [15]

Summary

Introduction

Chronic kidney disease (CKD) is characterized by abnormalities of kidney structure or function, and the prevalence of CKD is rising greatly in recent years and it has become a worldwide heath issue [1]. The eventual outcome of CKD may be end-stage kidney disease (ESKD), when patients need dialysis or transplantation to survive. The final common pathology of CKD is renal interstitial fibrosis (RIF). Fibrosis is a pathological state characterized by excess extracellular matrix (ECM) protein production and progressive accumulation. Transforming growth factor-β (TGF-β) has long been well known as potent regulator of ECM production and fibrogenesis, and they are induced during kidney injury. In renal biopsy samples from patients with CKD, some evidences typically suggested loss of peritubular capillaries in areas of tubulointerstitial fibrosis, leading to a reduction in oxygen supply. Hypoxia is a profibrogenic stimulus for tubular cells, interstitial fibroblasts and renal microvascular endothelial cells. Hypoxia has been proposed as an important microenvironmental factor in the development of tissue fibrosis.

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