低蛋白饮食加α-酮酸抑制CRF大鼠肾小管上皮间充质转化的作用及机制探讨

目的 观察低蛋白饮食(low protein diet,LPD)以及LPD+α-酮酸(α-ketoacid,α-KA)对腺嘌呤致慢性肾功能衰竭(chronic renal failure,CRF)大鼠模型肾小管上皮间充质转化(Epithelial-mesenehyrreal transition,EMT)及相关细胞因子...

Effects and Mechanism of Low Protein Diet Supplemented With α-ketoacid on renal tubular epithelial-mesenchymal transition in Adenine-induced Chronic Renal Failure Rats

Objective To observe the effect and mechanism of Low Protein Diet(LPD) supplemented with α-ketoacid (α-KA) on renal tubular epithelial-mesenchymal transition (EMT) in adenine-induced chronic renal failure in rats. Methods Forty-six male Wistar rats were divided into two parts:normal control rats(n=10)and CRF rats(n=36),which were treated with 150mg/(kg·day) adenine intragastrically. Adenine induced CRF rats were divided into three groups:a. NPD group(n=12); b. LPD group(n=12); c. LPD+α-KA group(n=12). All the rats were sacrificed at week 10,14. Expressions of Ecadherin,Transforming growth factorβ1(TGF-β1),Thrombospodin-1(TSP-1) and Vascular endothelial growth factor (VEGF) were detected by immunohistological,western blot and/or RT-PCR. Results At 10 week,E-cadherin expression in LPD and LPD+α-KA rats were significantly stronger than that in NPD rats,and that in LPD+α-KA was more effective than LPD. The expression of TGF-β1 and TSP-1 in LPD+α-KA group were markedly lower than in NPD at 10 week. Meanwhile,the expression of VEGF in LPD+α-KA group was significantly higher than that in NPD or LPD groups. Conclusions LPD and LPD+α-KA ameliorate EMT in adenine-induced CRF rat model,and these effects of LPD+α-KA is more better than LPD. The mechanism of the therapeutic effects of LPD+ α-KA is related to suppressing the overexpression of TGF-β1 and TSP-1 or the downregulation of VEGF. The exact mechanism needs to be studied further.