Kim Jin H, Lee Dong-Won, Jung Myeong H, Cho Hyun-Seop, Jeon Dae-Hong, Chang Se-Ho, Park Dong Jun
Biomedical Research Institute, Gyeongsang National University, Jinju, Republic of Korea.
Nephron Exp Nephrol. 2014;128(1-2):21-9. doi: 10.1159/000365851. Epub 2014 Nov 5.
This study was conducted to elucidate the role of renal macrophages in the development of acute kidney injury (AKI) in a glycerol (Gly)-induced rhabdomyolysis mouse model.
The experimental model of rhabdomyolysis requires injecting 50% Gly (10 ml/kg) intramuscularly into mice. Control mice were injected into the tail vein with the liposomal vehicle. Liposome-encapsulated clodronate (LEC)-only mice were injected with LEC. Gly-only mice were injected with Gly into a hind limb. LEC+Gly-treated mice were injected intravenously with 100 μl of LEC 24 h prior to Gly injection. Mice were sacrificed 24 h after Gly injection.
Gly injection increased the serum creatinine level, and induced tubular damage. Renal CD45(+)CD11b(+)Ly6c(+) or CD45(+)CD11b(+)Ly6c(+)F4/80(+) macrophages were decreased by pretreatment with LEC in both normal and injured kidneys. Macrophage depletion prevented Gly-induced apoptotic death of tubular epithelial cells by decreasing caspase-9, ERK and p53, while increasing Bcl-2 expression. Expression of the inflammatory mediators NF-κB, MCP-1, ICAM-1, iNOS and COX-2 were also decreased with LEC pretreatment of mice injected with Gly.
These results support the hypothesis that depletion of macrophages prevents renal dysfunction by abrogating apoptosis and attenuating inflammation during AKI.
本研究旨在阐明在甘油（Gly）诱导的横纹肌溶解小鼠模型中，肾巨噬细胞在急性肾损伤（AKI）发生发展中的作用。
横纹肌溶解实验模型需要给小鼠肌肉注射50%甘油（10 ml/kg）。对照小鼠经尾静脉注射脂质体载体。仅注射脂质体包裹氯膦酸盐（LEC）的小鼠注射LEC。仅注射甘油的小鼠后肢注射甘油。LEC + Gly处理的小鼠在注射甘油前24小时静脉注射100 μl LEC。注射甘油24小时后处死小鼠。
注射甘油会增加血清肌酐水平，并导致肾小管损伤。在正常和受损肾脏中，LEC预处理均会降低肾CD45(+)CD11b(+)Ly6c(+)或CD45(+)CD11b(+)Ly6c(+)F4/80(+)巨噬细胞数量。巨噬细胞耗竭通过降低半胱天冬酶-9、细胞外信号调节激酶（ERK）和p53，同时增加Bcl-2表达，预防了甘油诱导的肾小管上皮细胞凋亡性死亡。用LEC预处理注射甘油的小鼠后，炎症介质NF-κB、单核细胞趋化蛋白-1（MCP-1）、细胞间黏附分子-1（ICAM-1）、诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）的表达也降低。
这些结果支持以下假设，即巨噬细胞耗竭通过在急性肾损伤期间消除细胞凋亡和减轻炎症来预防肾功能障碍。
