| [Objective] The method of warming yang and replenishing qi is widely concerned and used in treating renal interstitial fibrosis (RIF). QiFu Decoction (QFD)(Wei Shi Jia Cang), an ancient prescription, using this method, has been used to treat RIF in China for many years. Nevertheless, the mechanisms in vivo remain unclear. Epithelial-mesenchymal transition (EMT) is an important mechanism in RIF. In the process of EMT, it is characterized by E-cadherin down-regulating, alpha-smooth muscle actin (alpha-SMA) high expression, along with many signaling pathway activated by fibrogenesis, inducing RIF eventually. Among them, extracellular signal-regulated protein kinase1/2(ERK1/2) signaling pathway is a classical one. Blocking the expression of the key molecular phosphorylated-ERK1/2(p-ERK1/2) in vivo could attenuate EMT, reduce fibrogenesis expression and improve RIF. Hence, the aim of this study was to investigate the effects of QFD in RIF model rats, established by adenine and unilateral ureteral obstruction (UUO), and explain the mechanisms of ameliorating RIF by regulating ERK1/2signaling pathway and following improving EMT in vivo.[Methods] Sprague Dawley (SD) rats were randomly divided into the Sham group with5rats (Group A), the Model group with10rats (Group B), the Qifu Decoction group with10rats (Group C) and the Enalapril group with10rats (Group D). Firstly, the rat in Group B, C and D were administrated with adenine (150mg/kg/day) for14days, and were operated with UUO on day21. The rats in Group A were opened the abdominal cavity and freed the left ureter. After the model was successfully established, the rats in Group C and D were administrated with Qifu Decoction (5g/kg-d), and the Enalapril suspension (20mg/kg-d), while the rats in Group A and B were administrated with distilled water. All rats were administrated for3weeks. Before administration and at the end of week1,2and3, the rats were weighted, and24h urinary protein excretion (Upro), urinary beta2-microglobulin (beta2-MG) and urinary N-acetyl-D-glucosaminidase (NAG) were examined, respectively. All rats were killed after administration for3weeks. Blood and renal tissues were collected, renal morphology, tubulointerstitial morphology, the expression of E-cadherin and alpha-smooth muscle actin (alpha-SMA), and the expression of transforming growth factor-betal (TGF-β1) and connective tissue growth factor (CTGF) and p-ERK1/2were evaluated. Meanwhile, serum creatinine (Scr), blood urea nitrogen (BUN) and uric acid (UA) were detected.[Results] We established the model rat successfully, which was characterized by renal pelvis effusion, ischemic appearance, renal dysfunction, low-molecular weight proteinuria, and extracellular matrix deposition in tubulointerstitial district. Qifu Decoction attenuated urinary β2-MG, NAG, and renal tubulointerstitial fibrosis, increased E-cadherin protein expression, and reduced a-SMA, TGF-β1, CTGF, and p-ERK1/2protein expression in kidney, however, it had no influence on renal function in vivo. In addition, these effects were better than those of the model rats treated by Enalapril.[Conclusion] Qifu Decoction could improve EMT and ameliorate RIF in model rats by up-regulating E-cadherin protein expression, down-regulating alpha-SMA, TGF-betal, and CTGF protein expression in kidney, as well as inhibiting p-ERK1/2protein expression, the key molecular in ERK1/2signaling pathway. |
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