Division of Nephrology and Hypertension, Department of Internal Medicine, St Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki 216-8511, Japan.
Hypertension. 2012 Oct;60(4):973-80. doi: 10.1161/HYPERTENSIONAHA.112.199828. Epub 2012 Aug 27.
To investigate the role of human liver-type fatty acid binding protein (hL-FABP) in angiotensin (Ang) II-induced renal injury, Ang II was infused systemically into hL-FABP chromosomal transgenic (Tg) and wild-type (WT) mice (Tg-Ang II and WT-Ang II) for 28 days. Control mice were injected with saline only (Tg-control and WT-control). hL-FABP was expressed in proximal tubules of Tg mice. After a high-dose injection of Ang II, renal gene and protein expressions of hL-FABP in Tg-Ang II mice increased significantly compared with Tg-control mice. Urinary excretion of L-FABP was significantly greater in Tg-Ang II than in Tg-control mice. Blood pressure levels in both groups increased to a similar extent. Upregulation of monocyte chemoattractant protein 1 expression, macrophage infiltration in the interstitium, tubulointerstitial damage, and depositions of type I and III collagens were observed in both Tg-Ang II and WT-Ang II mice. However, these effects were less pronounced in Tg-Ang II compared with WT-Ang II mice. The level of renal N-(hexanoyl)lysine, an oxidative stress marker, was significantly higher in WT-Ang II than in Tg-Ang II mice. In conclusion, renal hL-FABP reduced oxidative stress in Ang II-induced renal injury and attenuated tubulointerstitial damage.
为了研究人肝型脂肪酸结合蛋白（hL-FABP）在血管紧张素（Ang）II 诱导的肾损伤中的作用，将 Ang II 全身输注到 hL-FABP 染色体转基因（Tg）和野生型（WT）小鼠（Tg-Ang II 和 WT-Ang II）中 28 天。对照组小鼠仅注射生理盐水（Tg-对照和 WT-对照）。hL-FABP 在 Tg 小鼠的近端肾小管中表达。在高剂量 Ang II 注射后，与 Tg-对照小鼠相比，Tg-Ang II 小鼠的肾基因和 hL-FABP 蛋白表达显著增加。与 Tg-对照小鼠相比，Tg-Ang II 小鼠的 L-FABP 尿排泄明显增加。两组的血压水平均增加到相似的程度。在 Tg-Ang II 和 WT-Ang II 小鼠中均观察到单核细胞趋化蛋白 1 表达上调、间质中巨噬细胞浸润、肾小管间质损伤以及 I 型和 III 型胶原沉积。然而，与 WT-Ang II 小鼠相比，这些效应在 Tg-Ang II 小鼠中不那么明显。氧化应激标志物肾 N-（己酰）赖氨酸的水平在 WT-Ang II 小鼠中明显高于 Tg-Ang II 小鼠。总之，肾 hL-FABP 减轻了 Ang II 诱导的肾损伤中的氧化应激，并减轻了肾小管间质损伤。
