Administration of Astragalus Membranaceus prevented kidney dysfunction in cisplatin-AKI model mice
Administration of Astragalus Membranaceus prevented kidney dysfunction in cisplatin-AKI model mice
复制标题
服用黄芪可预防顺铂 AKI 模型小鼠的肾功能障碍
DOI：
10.1093/ndt/gfz106.fp292
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发表时间：
2019
影响因子：
6.1
通讯作者：
Kinoue Takaaki
中科院分区：
文献类型：
--
作者：
Kagemasa Kajiwara;Arai Makoto;Nakada Yoshinobu;Kinoue Takaaki
方法：夹持成年雄性小鼠左肾蒂60 min，立即行肾再灌注和右肾切除术。各组术前24 h分别给予抗RANKL抗体和重组RANKL。再灌注一段时间后，测定血清肌酐水平，并切除左肾。通过左肾组织学检查和western blotting检测RANKLRANK系统及I/R相关蛋白的表达和定位。结果：I/R损伤后血清肌酐水平显著升高。RANKL在24小时内呈时间依赖性增加，而RANKL在再灌注后12小时才被诱导。RANK在浸润性炎症细胞中表达，其中CD68（单核/巨噬细胞的标志物）阳性。与I/R组相比，抗rankl抗体显著损害肾功能，诱导炎性细胞因子增加。然而，与I/R组相比，重组RANKL显著改善了肾功能，减少了炎症细胞因子的诱导。结论：本研究首次评价了RANKLRANK系统在肾I/R损伤中的作用。RANKL-RANK信号通过影响巨噬细胞功能抑制炎症细胞因子，导致I/R损伤后肾功能改善。
METHODS: The left renal pedicle of adult male mice was clamped for 60 min, and reperfusion and right nephrectomy were performed immediately. Separate groups were administered anti-RANKL antibody and recombinant RANKL 24 h before surgery. After reperfusion for a set period of time, the serum creatinine level was measured, and the left kidney was removed. Histological examination and western blotting of the left kidney were performed to evaluate the expression and localization of the RANKLRANK system and proteins related to I/R. RESULTS:Serum creatinine levels were significantly elevated by I/R injury. A time-dependent increase of RANKL was observed up to 24 h, whereas RANK was induced until 12 h after reperfusion. RANK was expressed in infiltrating inflammatory cells, which were positive for CD68, a marker of monocytes/macrophages. Anti-RANKL antibody significantly impaired renal function and increased the induction inflammatory cytokines compared with those of the I/R group. However, recombinant RANKL significantly improved renal function and decreased the induction of inflammatory cytokines compared with those of the I/R group. CONCLUSIONS: The present study is the first to evaluate the role of the RANKLRANK system in renal I/R injury. RANKL-RANK signalling inhibits inflammatory cytokines by affecting macrophage function and leads to improved renal function following I/R injury.