Liver-type fatty acid-binding protein attenuates renal injury induced by unilateral ureteral obstruction
Liver-type fatty acid-binding protein attenuates renal injury induced by unilateral ureteral obstruction
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DOI：
10.2353/ajpath.2006.060131
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发表时间：
2006-10-01
影响因子：
6
通讯作者：
Kimura, Kenjiro
中科院分区：
文献类型：
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作者：
Kamijo-Ikemori, Atsuko;Sugaya, Takeshi;Kimura, Kenjiro
肝型脂肪酸结合蛋白（L-FABP）对长链脂肪酸氧化产物具有高度亲和力，可能是一种有效的内源性抗氧化剂。为了研究L-FABP在肾小管间质损伤中的作用，我们使用了单侧输尿管梗阻（UUO）模型。我们建立了人L-FABP（hL-FABP）基因转基因（Tg）小鼠，并比较了Tg小鼠（n = 23）和野生型（WT）小鼠（n = 23）的肾小管间质病理。在UUO后第2、4、5或7天处死小鼠。虽然小鼠L-FABP在WT小鼠中不表达，但hL-FABP在具有UUO的Tg小鼠（UUO-Tg）和假手术Tg小鼠的近端小管中表达。与假手术组相比，UUO-Tg组小鼠肾脏hL-FABP的表达明显增加。与UUO-WT肾相比，UUO-Tg肾中浸润肾小管的巨噬细胞（F4/80）数量以及MCP-1和MCP-3的表达水平显著降低。在UUO-Tg肾中，肾小管间质损伤的程度和I型胶原的沉积显著低于UUO-WT肾。第7天，脂质过氧化产物在UUO-WT肾脏中蓄积，但在UUO-Tg肾脏中未蓄积。总之，肾脏L-FABP可以降低UUO模型中的氧化应激，改善肾小管间质损伤。
Liver-type fatty-acid-binding protein (L-FABP), which has high affinity for long-chain fatty acid oxidation products, may be an effective endogenous antioxidant. To examine the role of L-FABP in tubulointerstitial damage, we used a unilateral ureteral obstruction (UUO) model. We established human L-FABP (hL-FABP) gene transgenic (Tg) mice and compared the tubulointerstitial pathology of the Tg mice (n = 23) with that of the wild-type (WT) mice (n = 23). Mice were sacrificed on days 2, 4, 5, or 7 after UUO. Although mouse L-FABP was not expressed in WT mice, hL-FABP was expressed in the proximal tubules of the Tg mice with UUO (UUO-Tg) and in sham-operated Tg mice. The expression of renal hL-FABP was significantly increased in UUO-Tg compared with sham-operated Tg mice. The number of macrophages (F4/80) infiltrating the interstitium and the level of expression of MCP-1 and MCP-3 were significantly lower in UUO-Tg kidneys compared with UUO-WT kidneys. In UUO-Tg kidneys, the degree of the tubulointerstitial injury and the deposition of type I collagen were significantly lower than that of UUO-WT kidneys. On day 7, lipid peroxidation product accumulated in the UUO-WT kidneys but not in that of UUO-Tg kidneys. In conclusion, renal L-FABP may reduce the oxidative stress in the UUO model, ameliorating tubulointerstitial damage.