Background Increased proliferating cell nuclear antigen (PCNA) expression, a marker of cellcycle progression, was recently documented in the remnant kidney (RK) model of progressive renal failure. Astragalin Icariine ...Background Increased proliferating cell nuclear antigen (PCNA) expression, a marker of cellcycle progression, was recently documented in the remnant kidney (RK) model of progressive renal failure. Astragalin Icariine and Anthraquinone derivatives were respectively extracted from Radix Astragali, Herba Epimedii and Radix Et Rhizoma Rhei which have been traditionally used for treatment of progressive renal diseases for a long time in China. In the present study, it was examined whether the combination of Astragalin Icariine and Anthraquinone (cAIA) could reduce PCNA expression and stabilize renal function in the remnant kidney model more effectively than NiaoDuQing Granula (Ndq) which is a combined Chinese medicine especial for chronic renal insufficiency(CRI). Methods Male Wistar rats were divided into 7 groups. Group 1 was normal control,group 2 sham operation control, Group 3 model control and 4 to 7 treated groups. Group 2 underwent a sham operation by decapsulation of the kidney and groups 3 to 7 underwent a right subeapsular nephreetomy with surgical resection of the upper and lower thirds of the left kidney. Groups 1 to 3 received 0.9% NaC1 10 ml/kg body weight,Groups 4 to 6 received cAIA 2 g/kg,4 g/kg,8 g/kg body weight,and group 7 received Ndq 3.6 g/kg body weight once daily for 8 weeks at the end of three months after surgery respectively. At the start of the protocol and half a month, one month and two months after administration, body weights and livability were determined, blood samples were obtained for biochemical evaluation, and the RK was collected for histological evaluation at the time of sacrifice. Results It was found that both of cAIA and Ndq resulted in improved blood urea nitrogen(BUN), serum cretinine(Scr), albumin(ALB), red blood cell counts(RBC), hemoglobin (Hb), calcium (Ca), phosphorus (P), superoxide dismutase (SOD),nitric oxidate (NO),body weights and livability compared with group 3 (cAIA and Ndq versus model,P <0.05,P <0.01) and higher doses of cAIA treatment could get better results. The livabihty and Hb were higher in cAIA 8 g/kg body weight than Ndq (P < 0.01). Renal histological integration confirmed an evident decrease in glomerular and interstitial fibrosis in cAIA 4 g/kg and 8 g/kg groups versus model(P < 0.05,P <0.01). Immunohistochemical staining and semiquantitative analyses showed a significant decrease in collagen Ⅳ (CoⅣ), total glomerular cells and PCNA positive cells in cAIA 4 g/kg and 8 g/kg groups versus model( P < 0.05, P < 0.01 ), and total glomerular cells in cAIA 8 g/kg versus Ndq group (P < 0.05). A comparable results in TP in cAIA and Ndq treated groups versus model was also noted. Conclusion There was a positive relationship between the PCNA expression and renal fibrosis, cAIA and Ndq administration could reduce PCNA expression, inhibit fibrosis and stabilize renal function in the RK model and higher doses of cAIA treatment could get better results than Ndq, especially in livability, Hb and total glomerular cells. With respect to potential therapeutic implications of the finding, it is of crucial importance to further investigate the effective mechanisms of Chinese Herbal extracts on progressive renal disease.展开更多
文摘Background Increased proliferating cell nuclear antigen (PCNA) expression, a marker of cellcycle progression, was recently documented in the remnant kidney (RK) model of progressive renal failure. Astragalin Icariine and Anthraquinone derivatives were respectively extracted from Radix Astragali, Herba Epimedii and Radix Et Rhizoma Rhei which have been traditionally used for treatment of progressive renal diseases for a long time in China. In the present study, it was examined whether the combination of Astragalin Icariine and Anthraquinone (cAIA) could reduce PCNA expression and stabilize renal function in the remnant kidney model more effectively than NiaoDuQing Granula (Ndq) which is a combined Chinese medicine especial for chronic renal insufficiency(CRI). Methods Male Wistar rats were divided into 7 groups. Group 1 was normal control,group 2 sham operation control, Group 3 model control and 4 to 7 treated groups. Group 2 underwent a sham operation by decapsulation of the kidney and groups 3 to 7 underwent a right subeapsular nephreetomy with surgical resection of the upper and lower thirds of the left kidney. Groups 1 to 3 received 0.9% NaC1 10 ml/kg body weight,Groups 4 to 6 received cAIA 2 g/kg,4 g/kg,8 g/kg body weight,and group 7 received Ndq 3.6 g/kg body weight once daily for 8 weeks at the end of three months after surgery respectively. At the start of the protocol and half a month, one month and two months after administration, body weights and livability were determined, blood samples were obtained for biochemical evaluation, and the RK was collected for histological evaluation at the time of sacrifice. Results It was found that both of cAIA and Ndq resulted in improved blood urea nitrogen(BUN), serum cretinine(Scr), albumin(ALB), red blood cell counts(RBC), hemoglobin (Hb), calcium (Ca), phosphorus (P), superoxide dismutase (SOD),nitric oxidate (NO),body weights and livability compared with group 3 (cAIA and Ndq versus model,P <0.05,P <0.01) and higher doses of cAIA treatment could get better results. The livabihty and Hb were higher in cAIA 8 g/kg body weight than Ndq (P < 0.01). Renal histological integration confirmed an evident decrease in glomerular and interstitial fibrosis in cAIA 4 g/kg and 8 g/kg groups versus model(P < 0.05,P <0.01). Immunohistochemical staining and semiquantitative analyses showed a significant decrease in collagen Ⅳ (CoⅣ), total glomerular cells and PCNA positive cells in cAIA 4 g/kg and 8 g/kg groups versus model( P < 0.05, P < 0.01 ), and total glomerular cells in cAIA 8 g/kg versus Ndq group (P < 0.05). A comparable results in TP in cAIA and Ndq treated groups versus model was also noted. Conclusion There was a positive relationship between the PCNA expression and renal fibrosis, cAIA and Ndq administration could reduce PCNA expression, inhibit fibrosis and stabilize renal function in the RK model and higher doses of cAIA treatment could get better results than Ndq, especially in livability, Hb and total glomerular cells. With respect to potential therapeutic implications of the finding, it is of crucial importance to further investigate the effective mechanisms of Chinese Herbal extracts on progressive renal disease.
