Uremic toxins adsorbed by AST-120 promote tubular hypertrophy and interstitial fibrosis in nephrectomized rats

Uremic toxins adsorbed by AST-120 promote tubular hypertrophy and interstitial fibrosis in nephrectomized rats
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DOI:
10.1159/000080935
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发表时间:
2005-01-01
影响因子:
2.8
通讯作者:
Takahashi, S
Takahashi, S
中科院分区:
医学4区
文献类型:
--
作者:
Okada, K;Matsumoto, K;Takahashi, S

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背景:尿毒症毒素可促进肾小球肥大。本研究旨在阐明尿毒症毒素与肾小管间质改变之间的关系。方法:雄性SD大鼠60只,行2/3肾切除术(Nx,n = 30)和4/5肾切除术(Nx,n = 30)。实验在手术后2周开始,并在8周的时间内进行。每组的一半(Nx-A)被给予1g/天的口服含碳吸附剂AST-120,成对喂养,另一半(Nx-C)作为对照。清除研究后第8周处死所有大鼠。结果如下:与2/3 Nx-C大鼠相比,2/3 Nx-A大鼠第8周的近端小管最短直径(PTD)和间质纤维化面积(IFA)显著降低(体重、收缩压、肾小球滤过率和尿蛋白排泄水平相似)。与4/5只体重和收缩压相似的Nx-C大鼠相比,4/5只Nx-A大鼠的PTD和IFA值、肾小球滤过率和尿蛋白排泄量在8周时显著降低。结论:AST-120给药可最大限度地减少近端肾小管肥大和间质纤维化的出现,随后可预防蛋白尿和肾功能下降的发生。本研究表明,AST-120吸附的尿毒症毒素促进肾切除大鼠肾小管肥大和间质纤维化。版权所有(C)2005 S. Karger AG,巴塞尔。
Background: Uremic toxins have been shown to promote glomerular hypertrophy. The present study was performed to elucidate the relation between uremic toxins and tubulointerstitial changes. Methods: Sixty male Sprague-Dawley rats underwent 2/3 nephrectomy (Nx; n = 30) and 4/5 Nx (n = 30). Experiments were initiated 2 weeks after surgery, and were performed over an 8-week period. Half of each group (Nx-A) was administered 1 g/day of an oral carbonaceous adsorbent, AST-120, with pair-feeding, and the other half (Nx-C) served as controls. All rats were sacrificed at week 8 after a clearance study. Results: The shortest diameter of proximal tubules (PTD) and interstitial fibrosis area (IFA) at week 8 in 2/3 Nx-A rats was significantly decreased compared to that in 2/3 Nx-C rats (similar body weights, systolic blood pressures, glomerular filtration rates, and urinary protein excretion levels). The values of PTD and IFA, glomerular filtration rate and urinary protein excretion level at week 8 in 4/5 Nx-A rats were significantly decreased compared to those in 4/5 Nx-C rats (similar body weights and systolic blood pressures). Conclusion: Administration of AST-120 minimized the appearance of proximal tubular hypertrophy and interstitial fibrosis, and subsequently prevented the occurrence of proteinuria and decreased renal function. The present study indicates that uremic toxins adsorbed by AST-120 promote tubular hypertrophy and interstitial fibrosis in nephrectomized rats. Copyright (C) 2005 S. Karger AG, Basel.