Department of Anesthesiology, Cangzhou Central Hospital, Teaching Hospital of Tianjin Medical University, Cangzhou 061000, Hebei, China.
Department of Anesthesiology, Cangzhou Central Hospital, Teaching Hospital of Tianjin Medical University, Cangzhou 061000, Hebei, China.
Mater Sci Eng C Mater Biol Appl. 2021 Dec;131:112536. doi: 10.1016/j.msec.2021.112536. Epub 2021 Nov 8.
Ischemia-reperfusion (I/R) injury causes high morbidity, mortality, and healthcare costs. I/R induces acute kidney injury through exacerbating the mitochondrial damage and increasing inflammatory and oxidative responses. Here, we developed the mitochondria-targeted nanocarrier to delivery of Coenzyme Q10 (CoQ10) for renal I/R treatment in animal model. The mitochondria-targeted TPP CoQ10 nanoparticles (T-NP) were synthesized through ABC miktoarm polymers method and characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The I/R mouse model and oxygen-glucose deprivation/reperfusion (D/R) model were created to examine the role of T-NP on renal I/R. Mitochondrial DNA damage, apoptosis, and inflammatory cytokines were measured in I/R injury mice. Plasma creatinine, urea nitrogen, tubular injury score was tested to assess the renal function. T-NP nanoparticles could be delivered to renal mitochondria preciously and efficiently. T-NP administration attenuated oxidative injury in both cell and animal models significantly, alleviated mtDNA damage, suppressed inflammatory and apoptotic responses, and improved renal function. The mitochondria specific CoQ10 delivery provided a precious and efficient method for protecting inflammatory and oxidative responses of I/R-induced renal damage.
缺血再灌注（I/R）损伤会导致高发病率、高死亡率和高医疗成本。I/R 通过加剧线粒体损伤、增加炎症和氧化反应导致急性肾损伤。在这里，我们开发了一种线粒体靶向纳米载体，用于在动物模型中输送辅酶 Q10（CoQ10）以治疗肾 I/R。通过 ABC 多臂聚合物方法合成了线粒体靶向 TPP CoQ10 纳米颗粒（T-NP），并通过动态光散射（DLS）和透射电子显微镜（TEM）进行了表征。创建了 I/R 小鼠模型和氧葡萄糖剥夺/再灌注（D/R）模型，以检查 T-NP 对肾 I/R 的作用。在 I/R 损伤小鼠中测量了线粒体 DNA 损伤、细胞凋亡和炎症细胞因子。检测血浆肌酐、尿素氮、肾小管损伤评分以评估肾功能。T-NP 纳米颗粒可以精确有效地递送到肾线粒体。T-NP 给药在细胞和动物模型中均显著减轻氧化损伤，减轻 mtDNA 损伤，抑制炎症和细胞凋亡反应，并改善肾功能。线粒体特异性 CoQ10 递药为保护 I/R 诱导的肾损伤的炎症和氧化反应提供了一种珍贵而有效的方法。
