Tanaka Tamami, Doi Kent, Maeda-Mamiya Rui, Negishi Kousuke, Portilla Didier, Sugaya Takeshi, Fujita Toshiro, Noiri Eisei
Department of Nephrology and Endocrinology, University Hospital, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
Am J Pathol. 2009 Apr;174(4):1203-11. doi: 10.2353/ajpath.2009.080511. Epub 2009 Mar 5.
This study aimed to elucidate the role of L-type fatty acid-binding protein (L-FABP) in renal tubulointerstitial injury using a mouse adenine-induced renal injury model. C57BL/6 mice fed excess dietary adenine for 6 weeks showed a gradual increase in levels of blood urea nitrogen (BUN). They also showed severe tubulointerstitial pathological findings, such as fibrosis and macrophage infiltration without glomerular damage, which were attenuated by treatment with either allopurinol or Y-700, a new xanthine dehydroxygenase inhibitor. Because renal expression of L-FABP is defective in C57BL/6 mice, human L-FABP transgenic mice were fed an adenine-containing diet. Transgenic mice showed lower BUN levels and lower levels of pathological injury compared with wild-type mice. On the other hand, urinary levels and renal expression of L-FABP in the adenine group was significantly increased and attenuated by treatment with either allopurinol or Y-700. Urinary L-FABP was positively correlated with BUN levels and pathological damages in the tubulointerstitium. No increases in urinary protein, albumin, or N-acetyl-beta-D-glucosaminidase levels were found for 6 weeks in any group. In conclusion, we demonstrated that urinary L-FABP levels can be used to monitor both dynamics and drug responses in a mouse adenine-induced tubulointerstitial injury model.
本研究旨在利用小鼠腺嘌呤诱导的肾损伤模型阐明L型脂肪酸结合蛋白(L-FABP)在肾小管间质损伤中的作用。喂食过量腺嘌呤6周的C57BL/6小鼠血尿素氮(BUN)水平逐渐升高。它们还表现出严重的肾小管间质病理表现,如纤维化和巨噬细胞浸润,但无肾小球损伤,用别嘌呤醇或新型黄嘌呤脱氢酶抑制剂Y-700治疗可减轻这些表现。由于C57BL/6小鼠的L-FABP肾表达存在缺陷,因此给人L-FABP转基因小鼠喂食含腺嘌呤的饮食。与野生型小鼠相比,转基因小鼠的BUN水平和病理损伤水平较低。另一方面,腺嘌呤组中L-FABP的尿水平和肾表达显著增加,用别嘌呤醇或Y-700治疗可使其降低。尿L-FABP与BUN水平和肾小管间质病理损伤呈正相关。6周内任何组均未发现尿蛋白、白蛋白或N-乙酰-β-D-氨基葡萄糖苷酶水平升高。总之,我们证明尿L-FABP水平可用于监测小鼠腺嘌呤诱导的肾小管间质损伤模型中的动态变化和药物反应。