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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-mesenchymal transition,EMT)及相关细胞因子表达变化的影响。方法 46只雄性Wistar大鼠分为对照组(n=10),CRF模型组(n=36)。CRF模型组予150mg/(kg·day)腺嘌呤灌胃,造模成功后随机分入NPD组(n=12)、LPD组(n=12)和LPD+α-KA组(n=12),分别于第10、14周末留取肾组织。免疫组化方法测定肾组织中E-钙粘蛋白(E-cadherin)、转化生长因子β1(TGF-β1)、血小板反应蛋白-1(TSP-1)及血管内皮生长因子(VEGF)的表达,Western blot方法测定VEGF的表达,RT-PCR方法测定TSP-1及VEGF mRNA表达。结果 10周、14周时LPD、LPD+α-KA组E-cadherin表达比NPD组显著增强,LPD+α-KA这一作用更显著。10周时,LPD+α-KA组TGF-β1、TSP-1表达显著低于NPD组,LPD+α-KA组VEGF表达水平比NPD组及LPD组显著增强。结论在本实验条件下,LPD+α-KA及LPD均显示减缓腺嘌呤CRF大鼠肾间质EMT的作用,LPD+α-KA的作用更强。两种限蛋白饮食对CRF模型肾组织EMT的抑制作用可能与其下调TGF-β1、TSP-1的表达及上调VEGF的表达相关,但确切机制有待进一步研究。
Objective To observe the effects of low protein diet (LPD) and LPD α-ketoacid (α-KA) on the expression of interleukin-1β in the rat model of chronic renal failure (CRF) Epithelial-mesenchymal transition (EMT) and related cytokine expression changes. Methods 46 male Wistar rats were divided into control group (n = 10) and CRF model group (n = 36). CRF model group was given adenine 150mg / (kg · day) gavage, after successful modeling were randomly divided into NPD group (n = 12), LPD group (n = 12) and LPD + α-KA group (n = 12) , Respectively, at the end of the first 10, 14 to take kidney tissue. The expression of E-cadherin, transforming growth factor β1 (TGF-β1), TSP-1 and vascular endothelial growth factor (VEGF) The expression of VEGF was detected by Western blot and the mRNA expression of TSP-1 and VEGF was detected by RT-PCR. Results The expression of E-cadherin in LPD and LPD + α-KA group was significantly increased than that in NPD group at 10 weeks and 14 weeks, and the effect of LPD + α-KA was more significant. At 10 weeks, the expression of TGF-β1 and TSP-1 in LPD + α-KA group was significantly lower than that in NPD group. The expression of VEGF in LPD + α-KA group was significantly higher than that in NPD group and LPD group. Conclusions Both LPD + α-KA and LPD show an effect of attenuating EMT of renal interstitium in adenine-CRF rats under the experimental conditions, and the effect of LPD + α-KA is stronger. The inhibitory effects of two protein-limited diets on EMT in CRF model rats may be related to the downregulation of TGF-β1, TSP-1 and up-regulation of VEGF expression, but the exact mechanism remains to be further studied.