低蛋白加α-酮酸饮食对5/6肾大部切除大鼠营养物质代谢及残肾组织硬化的影响  

Effects of low protein diet with α-ketoacids supplement on metabolism and residual kidney fibrosis in 5/6 nephrectomized rats

作　　者：龙泉[1] 李海明[1] 张力胤[1] 邱君思[1] 顾勇[1] 林善锬[1] 陈靖[1] 

机构地区：[1]复旦大学附属华山医院肾脏科,复旦大学肾脏病研究所,上海200040

出　　处：《上海医学》2009年第3期240-245,I0006,共7页Shanghai Medical Journal

基　　金：教育部新世纪优秀人才基金;德国费森尤斯公司2007年科研奖励基金资助项目

摘　　要：目的观察低蛋白加α-酮酸饮食对5/6肾大部切除大鼠营养物质代谢及残肾组织硬化的影响。方法30只雄性SD大鼠行5/6肾大部切除术建立慢性肾衰竭模型,1周后予不同饲料喂养,根据喂养方式分组如下:正常蛋白组(NPD组)予18%酪蛋白,低蛋白组(LPD组)予6%酪蛋白,低蛋白+α-酮酸组(LK组)予5%酪蛋白+1%α-酮酸,每组10只。另取10只雄性SD大鼠行假手术后予正常蛋白(18%酪蛋白)饲料喂养作对照组(Sham组)。12周后麻醉处死大鼠,留取血、尿标本,应用糖原染色法(过碘酸雪夫反应)观察残肾组织病理改变,应用免疫组织化学和Western印迹法检测残肾组织中转化生长因子(TGF)-β1的表达。结果建模3个月后,各组大鼠血压、体重、血白蛋白和总蛋白水平的差异均无统计学意义(P值均>0.05)。NPD、LPD、LK组大鼠血磷、iPTH、稳态模型评估胰岛素抵抗指数(HOMA-IR)和三酰甘油水平均较Sham组显著升高(P值均<0.05),而LK组大鼠各项指标均较LPD和NPD组显著降低(P值均<0.05)。NPD、LPD、LK组血CO2结合力显著低于Sham组(P值均<0.05),LK组又显著高于NPD和LPD组(P值均<0.05)。NPD、LPD、LK组大鼠血肌酐水平较Sham组显著升高(P值均<0.05),但前3组间的差异均无统计学意义(P值均>0.05)。NPD、LPD、LK组大鼠尿蛋白水平较Sham组显著增高(P值均<0.05),其中LK组尿蛋白总量较NPD和LPD组显著降低(P值均<0.05)。NPD、LPD、LK组大鼠的肾小球病理硬化积分(GSI)和肾小球细胞外基质/肾小球面积之比均显著高于Sham组(P值均<0.05),LK、LPD组又显著低于NPD组(P值均<0.05)。iPTH(r=0.704)、三酰甘油(r=0.455)、胆固醇(r=0.348)与血肌酐水平呈正相关(P值均<0.05),CO2结合力(r=-0.848)与血肌酐水平呈负正相关(P<0.05)。iPTH(r=0.685)、三酰甘油(r=0.506)与TGF-β1呈正相关(P值均<0.05),CO2结合力(r=-0.779)与TGF-β1呈负相关(P<0.05)。结论在5/6肾大部切除大鼠中,低蛋白加α-酮酸饮食在保证全身�Objective To observe the influence of low protein diet with α-ketoacids supplement on metabolism and residual kidney fibrosis in 5/6 nephrectomized rats. Methods Chronic renal failure model was established by 5/6 nephrectomy in 30 male Sprague-Dawley rats, then the animals were randomly assigned to the following diet groups： normal protein group （NPD： 18% casein protein）, low protein group（LPD, 6% casein protein） and supplemented low protein group （LK：5% casein protein ＋ 1% α-keto acids）. Ten male Sprague- Dawley sham-operated rats giving 18% casein protein served as control group（Sham）. All rats were killed at the end of the 12^th week and the blood and urine samples were collected. Pathologic changes of the residual kidney tisses were investigated using PAS staining. Immunohistochemistry and Western blotting were employed to detect the expression of transforming growth factor （TGF）-β1 in the residual kidney. Results Blood pressure, weight, serum albumin and total protein were not significantly different among the four groups. The phosphrous, iPTH, HOMA-IR and triglyceride levels in Nx groups were significantly higher than in the sham group, but those in the LK group were significantly lower than in LPD and NPD groups （ P〈 0.05）. CO2-CP was obviously lower in Nx groups, but higher in LK group than in NPD and LPD groups （P〈0.05）. Serum creatine of Nx groups was significantly higher compared to the sham group （P〈0.05）, but without significance among the Nx groups. Proteinuria level of Nx groups was markedly higher than that of the sham group （P〈0.05）, and that of the LK group was lower than those of NPD and LPD groups （P〈 0.05）. Pathological results suggested glomerular sclerosis index （GSI） and excelluar matrix score of Nx group were significantly higher than those of the sham group （P〈0.05）. by Both immunohistochemistry and Western blotting showed that TGF-131 expression was remarkably elevated in NPD group （P〈0.05）, and was significant

关 键 词：低蛋白饮食 Α-酮酸 肾大部切除 慢性肾衰竭 

分 类 号：R692.9[医药卫生—泌尿科学]