Kamijo-Ikemori Atsuko, Sugaya Takeshi, Obama Ayako, Hiroi Junya, Miura Hiroshi, Watanabe Minoru, Kumai Toshio, Ohtani-Kaneko Ritsuko, Hirata Kazuaki, Kimura Kenjiro
Internal Medicine, Nephrology and Hypertension, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki 216-8511, Japan.
Am J Pathol. 2006 Oct;169(4):1107-17. doi: 10.2353/ajpath.2006.060131.
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.
肝型脂肪酸结合蛋白(L-FABP)对长链脂肪酸氧化产物具有高亲和力,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,并将Tg小鼠(n = 23)与野生型(WT)小鼠(n = 23)的肾小管间质病理学进行了比较。在UUO后第2、4、5或7天处死小鼠。虽然WT小鼠不表达小鼠L-FABP,但hL-FABP在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Tg小鼠相比,UUO-Tg小鼠肾hL-FABP的表达显著增加。与UUO-WT肾相比,UUO-Tg肾间质中浸润的巨噬细胞(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,肾小管间质损伤程度和I型胶原沉积明显低于UUO-WT肾。在第7天,脂质过氧化产物在UUO-WT肾中积累,但在UUO-Tg肾中未积累。总之,肾L-FABP可能降低UUO模型中的氧化应激,改善肾小管间质损伤。