Urinary excretion of fatty acid-binding protein reflects stress overload on the proximal tubules
Urinary excretion of fatty acid-binding protein reflects stress overload on the proximal tubules
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DOI：
10.1016/s0002-9440(10)63384-6
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发表时间：
2004-10-01
影响因子：
6
通讯作者：
Kimura, K
中科院分区：
文献类型：
--
作者：
Kamijo, A;Sugaya, T;Kimura, K
人近端肾小管表达的参与游离脂肪酸(FFA)代谢的人五型脂肪酸结合蛋白(hl-FABP)是反映慢性肾脏疾病临床预后的重要指标。在此，我们研究了hl-FABP在蛋白超负荷肾病模型中的病理生理学意义。由于L-FABP基因在野生型小鼠中不表达，因此我们产生了hl-FABP染色体基因转基因(TG)小鼠。给转基因小鼠腹腔注射含有游离脂肪酸的牛血清白蛋白(BSA)(r-BSA组)或去FFA的BSA(d-BSA组)。与d-BSA组相比，r-BSA组大鼠肾小管间质损伤明显加重。重组牛血清白蛋白组大鼠肾脏hl-FABP基因表达上调，尿hl-FABP排泄量明显高于d-BSA组。此外，与注射r-BSA的野生型窝产仔相比，其产仔数明显减少。在第28天，注射它的转基因小鼠巨噬细胞的P值显著降低。在50例肾病患者中，尿hl-FABP与尿蛋白和肾小管间质损伤程度呈正相关。总之，我们的实验模型表明，hl-FABP的尿排出反映了近端小管上的压力，如尿蛋白超载。临床观察支持这一假说。
Urinary excretion of human fiver-type fatty acid-binding protein (hL-FABP), which is expressed in human proximal tubules and engaged in free fatty acid (FFA) metabolism, was reported to reflect the clinical prognosis of chronic kidney disease. Here we have investigated the pathophysiological significance of hL-FABP in a model of protein overload nephropathy. Because L-FABP is not expressed in the wild-type mice, we generated hL-FABP chromosomal gene transgenic (Tg) mice. Tg mice were intraperitoneally injected with bovine serum albumin (BSA) replete with FFAs (r-BSA group) or FFA-depleted BSA (d-BSA group). The r-BSA group developed significantly more severe tubulointerstitial damage than did the d-BSA group. Renal expression of the hL-FABP gene was more up-regulated, and urinary excretion of hL-FABP was significantly higher, in the r-BSA group than in the d-BSA group. Furthermore, compared with their wild-type littermates injected with r-BSA, the number. p of infiltrated macrophages was significantly attenuated in Tg mice injected with it on day 28. In patients with kidney disease (n = 50), urinary hL-FABP was correlated with both urinary protein and the severity of tubulointerstitial injury. In conclusion, our experimental model suggests that urinary excretion of hL-FABP reflects stresses, such as urinary protein overload, on the proximal tubules. The clinical observations support this hypothesis.