Abstract

Chronic kidney disease (CKD) is a global public health problem. Renin–angiotensin system (RAS) blockade is the mainstay of CKD therapy with limitations. Jian-Pi-Yi-Shen formula (JPYSF) is a traditional herbal decoction and has been used for treating CKD for decades. The purpose of the present study was to investigate the intervention effects of combined used of perindopril erbumine (PE) and JPYSF on CKD progression and explore their underlying mechanisms. CKD rat model was induced by feeding a diet containing 0.75% w/w adenine for 3 weeks. CKD rats were treated with PE or JPYSF or PE+JPYSF from the induction of CKD and lasted 4 weeks. Renal function was evaluated by serum creatinine (Scr) and blood urea nitrogen (BUN). Pathological lesions were observed by Periodic acid–Schiff (PAS) and Masson’s trichrome staining. The protein expression was tested by Western blot and immunohistochemistry analysis. The morphology of mitochondria was observed by transmission electron microscope. The results showed that combined used of PE and JPYSF could better improve renal function and pathological lesions and ameliorate renal fibrosis in CKD rats. Administration of PE and JPYSF enhanced sirtuin 3 (SIRT3) expression, inhibited mitochondrial fission, promoted mitochondrial fusion, and suppressed oxidative stress in the kidney of CKD rats. In conclusion, combined use of PE and JPYSF protected against CKD more effectively than either alone. The underlying mechanism may be associated with activation of SIRT3, modulation of mitochondrial dynamics, and antioxidant effects.

Highlights

  • Chronic kidney disease (CKD) is a common non-communicable disease that has become a significant public health concern

  • Either perindopril erbumine (PE) or Jian-Pi-Yi-Shen formula (JPYSF) could significantly mitigate the increases in serum creatinine (Scr) and blood urea nitrogen (BUN) in CKD rats (P

  • The combination of PE and JPYSF further reduced the levels of Scr and BUN compared with the CKD+PE or the CKD+JPYSF group (P

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Summary

Introduction

Chronic kidney disease (CKD) is a common non-communicable disease that has become a significant public health concern. CKD has a high global prevalence with a consistent estimated global CKD prevalence of between 11 and 13% with the majority stage 3 [1]. CKD is an irreversible disease, and it is always associated with cardiovascular comorbidities and premature death. As CKD progresses to end-stage kidney disease (ESKD), patients need renal replacement therapy in the form of dialysis or kidney transplantation to maintain their lives. It is estimated that more than 3 million ESKD patients are receiving dialysis therapy [2,3]. Despite the global burden and costs of CKD are immense, current therapeutic approaches for CKD are still limited. There is an urgent need to explore the optimal treatment strategies to retard CKD progression

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