Department of Kidney Transplantation, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
Nanomedicine (Lond). 2024;19(24):2011-2026. doi: 10.1080/17435889.2024.2382667. Epub 2024 Aug 8.
To target the reactive oxygen species (ROS) accumulation and renal tubular epithelial cell (rTEC) death in renal ischemia-reperfusion injury (IRI), we constructed a nanoparticle that offers ROS scavenging and rTEC-death inhibition: mesoporous zinc-tannic acid nanozyme (ZnTA). After successfully constructing ZnTA, we proceeded to examine its effect on ROS accumulation, cellular ferroptosis and apoptosis, as well as injury severity. Malondialdehyde, Fe amounts and 4-HNE staining demonstrated that ZnTA effectively attenuated rTEC ferroptosis. TUNEL staining confirmed that Zn carried by ZnTA could effectively inhibit caspase 3 and caspase 9, mitigating apoptosis. Finally, it reduced renal IRI through the synergistic effect of ROS scavenging and cell-death inhibition. This study is expected to provide a paradigm for a combined therapeutic strategy for renal IRI.
为了靶向肾缺血再灌注损伤（IRI）中的活性氧（ROS）积累和肾小管上皮细胞（rTEC）死亡，我们构建了一种提供 ROS 清除和 rTEC 死亡抑制的纳米颗粒：介孔锌单宁酸纳米酶（ZnTA）。成功构建 ZnTA 后，我们研究了其对 ROS 积累、细胞铁死亡和细胞凋亡以及损伤严重程度的影响。丙二醛、铁含量和 4-HNE 染色表明 ZnTA 可有效减轻 rTEC 的铁死亡。TUNEL 染色证实 ZnTA 携带的 Zn 可有效抑制半胱氨酸天冬氨酸蛋白酶 3 和半胱氨酸天冬氨酸蛋白酶 9，从而抑制细胞凋亡。最后，它通过 ROS 清除和细胞死亡抑制的协同作用减轻了肾 IRI。这项研究有望为肾 IRI 的联合治疗策略提供范例。
