Effects and mechanisms of Qifu decoction ameliorating renal tubulointerstitial fibrosis through inhibiting ERK1/2 signaling pathway in unilateral ureteral obstruction rats with yang deficiency / 中国中药杂志

<p><b>OBJECTIVE</b>To demonstrate the effects and mechanisms of Qifu decoction( QFD) on renal interstitial fibrosis (RIF) in model rats with yang-deficiency syndrome.</p><p><b>METHOD</b>The rats were randomly divided into 3 groups, the Sham group (Group A), the Model group (Group B), the Qifu decoction group (Group C) and the Enalapril group (Group D). The RIF model was established by adenine administrated and unilateral ureteral obstruction (UUO) of the left ureter. After the model was successfully established, the rats in Group C and D were administrated with QFD or the Enalapril suspension,while the rats in Group A and B were administrated with distilled water. All rats were administrated for 3 weeks. Before administration and at the end of week 1, 2 and 3, the rats were weighted, and 24 h urinary protein excretion (Upro), urinary β2-microglobulin (Uβ2-MG) and urinary N-acetyl-D-glucosaminidase (NAG) were examined, respectively. All rats were killed after administration for 3 weeks. Blood and renal tissues were collected, renal morphology and tubulointerstitial morphology were evaluated, respectively. Serum cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), blood urea nitrogen (BUN), serum creatinine (Scr) and uric acid (UA) were detected, respectively. The protein expressions of E-cadherin, α-smooth muscle actin(α-SMA), transforming growth factor-β1 (TGF-β1), onnective tissue growth factor (CTGF) extracellular signal-regulated protein kinase 1/2(ERK1/2) and phosphorylated-ERK1/2 (p-ERK1/2) in kidney were evaluated, respectively.</p><p><b>RESULT</b>QFD ameliorated serum cAMP level and the rate of cAMP/cGMP, attenuated urinary β2-MG level, NAG level and renal tubulointerstitial fibrosis, increased E-cadherin protein expression, and reduced α-SMA, TGF-β1, CTGF and p-ERK1/2 protein expressions in the kidney. However, QFD had no influence on renal function in vivo. In addition, these effects were better than those of the model rats treated by Enalapril.</p><p><b>CONCLUSION</b>QFD could alleviate yang-deficiency parameters, as well as urinary β2-MG level and NAG level in model rats induced by adenine administration and UUO. Moreover, QFD could improve EMT and RIF by up-regulating E-cadherin protein expression, and down-regulating α-SMA, TGF-β1, CTGF and p-ERK1/2 protein expressions, the key molecular in ERK1/2 signaling pathway.</p>

Regulative mechanisms of tubular epithelial to mesenchymal transition and interventional effects of Chinese herbal medicine / 中国中药杂志

Epithelial to mesenchymal transition (EMT) has been proposed as a key role leading to the progressive tubulo-interstitial fibrosis (TIF). The tubular EMT is an highly regulated process involving four key steps including: loss of epithelial cell adhesion, de novo smooth muscle actin expression and actin reorganization, disruption of tubular basement membrane,and enhanced cell migration and invasion. These crucial processes are closely connected to the relative actions on many signaling pathways in EMT. Additionally, increasing evidences suggest that some Chinese herbal medicines and their extracts, such as Astragali Radix, Cordyceps, Salvia miltiorrhiza, as well as Chinese. herbal prescriptions including Astragalus Angelica mixture and Supplementing Qi and activating blood circulation decoction, could intervene the related events controlling EMT both in vitro and in vivo. Chinese herbal medicines could ameliorate TIF by intervening the course of EMT.