低蛋白加α酮酸饮食对5/6肾切除大鼠残肾组织炎症因子表达及病理变化的影响

叶菡洋;袁伟杰;张志强;边琪;于建平;傅鹏;梅小斌;郭云珊;崔若兰

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中华肾脏病杂志 ›› 2007, Vol. 23 ›› Issue (6) : 394-399.
基础研究

低蛋白加α酮酸饮食对5/6肾切除大鼠残肾组织炎症因子表达及病理变化的影响

  • 叶菡洋;袁伟杰;张志强;边琪;于建平;傅鹏;梅小斌;郭云珊;崔若兰
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Study on the renoprotective effect of low protein diet supplemented with ketoacid in 5/6 nephrectomized rats

  • YE Han-yang;YUAN Wei-jie;ZHANG Zhi-qiang;BIAN Qi;YU Jian-ping;FU Peng;MEI Xiao-bin;GUO Yun-shan;CUI Ruo-lan
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摘要

目的 观察低蛋白加α酮酸饮食对5/6肾切除大鼠模型的残余肾功能保护作用及对肾组织炎症反应的影响,并探讨其可能的作用机制。 方法 30只SD雄性大鼠随机分为3组后行5/6肾切除,术后给予不同的饮食:低蛋白加酮酸组(4%酪蛋白+2%α酮酸)、低蛋白组(6%酪蛋白)和高蛋白组(20%酪蛋白),同时设10只SD雄性大鼠为假手术对照组(20%酪蛋白)。检测术前及术后第4、8、12周各组尿蛋白、血白蛋白、Scr、BUN等指标。12周后处死大鼠,观察肾组织病理改变;免疫组化方法检测肾组织单核巨噬细胞抗原(ED-1)、单核细胞化学吸引蛋白质1(MCP-1)及RANTES的表达情况。 结果 (1) 术后4周起,3个切除组Scr、BUN及尿蛋白均持续升高,其中以高蛋白组最显著(P < 0.01),而低蛋白加酮酸组升高最为缓慢;第12周时,低蛋白加酮酸组显著低于其余2组[Scr为(125.44±5.50)比(172.00±9.54)、(135.22±5.78) ?滋mol/L;尿蛋白量(24 h)为(28.36±3.69)比(92.32±34.06)、(46.62±6.19) mg,P < 0.01。(2) 与高蛋白组和低蛋白组相比,低蛋白加酮酸组肾组织损害明显减轻,肾小球病理积分为0.38±0.13比0.84±0.28、0.49±0.11,P < 0.01。(3) 低蛋白加酮酸组肾小管间质内MCP-1、RANTES的表达比高蛋白组及低蛋白组显著减少,同时ED-1的阳性细胞数也明显减少[肾小管间质ED-1阳性细胞为(3.59±0.78)个比(13.33±1.20)、(6.50±0.99)个,P < 0.05]。 结论 低蛋白加酮酸饮食可改善5/6肾切除大鼠的血脂及肾功能,并可能通过抑制肾组织的慢性炎症反应,减轻残肾组织肾小球硬化和肾间质的病变程度,减少尿蛋白的排泄,从而延缓大鼠慢性肾衰的进展。

Abstract

Objective To observe the effect of low protein diet supplemented with ketoacid on the protection of remnant kidney and the inhibition of inflammation infiltration in 5/6 nephrectomized rats. Methods Thirty male Sprague-Dawley rats were randomly assigned to following 3 groups and given different diets: low protein supplemented with ketoacid group(4% casein protein+2%ketoacid), low protein group(6% casein protein) and high protein group (20% casein protein). Ten SD rats were uses as sham-operation group(20% casein protein). The former three groups were subjected to 5/6 nephrectomy. Urine and blood samples were collected before operation and 4, 8 and 12 weeks after operation. All rats were killed after 12 weeks and pathologic changes of kidney tissue were investigated by microscope. Immunohistochemistry was also employed to investigate the expression of MCP-1, RANTES, ED-1 within the residual kidney. Results Scr and BUN of operated rats increased gradually. Compared with high protein group and low protein group, Scr and BUN of low protein supplemented with ketoacid group were significantly lower[Scr (125.44±5.50) vs (172.00±9.54), (135.22±9.54) μmol/L, P<0.01]. The urinary albumin excretion (UAE) increased significantly at the 4th week and reached the peak at the 12th week. The UAE (mg/24 h) of low protein supplemented ketoacid group (28.36±3.69)was markedly lower than that of high protein group(92.32±34.06) and low protein group(46.62±6.19). Compared with the latter two groups, pathological lesion of low protein supplemented with ketoacid group was obviously improved (glomerular pathological score 0.38±0.13 vs 0.84±0.28, 0.49±0.11, P<0.01). The expression levels of MCP-1, RANTES, ED-1 in operation groups were significantly higher than those in sham-operation group, and above expression levels in low protein supplemented with ketoacid group were the lowest among three operation groups (positive ED-1 cell 3.59±0.78 vs 13.33±1.20, 6.50±0.99, P<0.01). Conclusion Low protein diet supplemented with ketoacid can attenuate pathological lesion of residual kidney through certain mechanisms such as inhibition of inflammatory infiltration.

关键词

膳食 / 限制蛋白质 / 酮酸类 / 肾切除术 / 单核细胞化学吸引蛋白质1 / 单核巨噬细胞抗原1 / RANTES

Key words

Diet / protein-restricted / Ketoacids / Nephrectomy / Monocyte chemoattractant protein-1 / ED-1 / RANTES

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叶菡洋;袁伟杰;张志强;边琪;于建平;傅鹏;梅小斌;郭云珊;崔若兰. 低蛋白加α酮酸饮食对5/6肾切除大鼠残肾组织炎症因子表达及病理变化的影响[J]. 中华肾脏病杂志, 2007, 23(6): 394-399.
YE Han-yang;YUAN Wei-jie;ZHANG Zhi-qiang;BIAN Qi;YU Jian-ping;FU Peng;MEI Xiao-bin;GUO Yun-shan;CUI Ruo-lan. Study on the renoprotective effect of low protein diet supplemented with ketoacid in 5/6 nephrectomized rats[J]. Chinese Journal of Nephrology, 2007, 23(6): 394-399.
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