Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Magn Reson Med. 2018 Jun;79(6):3144-3153. doi: 10.1002/mrm.26985. Epub 2017 Nov 16.
To design a fluorine MRI/MR spectroscopy approach to quantify renal vascular damage after ischemia-reperfusion injury, and the therapeutic response to antithrombin nanoparticles (NPs) to protect kidney function.
A total of 53 rats underwent 45 min of bilateral renal artery occlusion and were treated at reperfusion with either plain perfluorocarbon NPs or NPs functionalized with a direct thrombin inhibitor (PPACK:phenyalanine-proline-arginine-chloromethylketone). Three hours after reperfusion, kidneys underwent ex vivo fluorine MRI/MR spectroscopy at 4.7 T to quantify the extent and volume of trapped NPs, as an index of vascular damage and ischemia-reperfusion injury. Microscopic evaluation of structural damage and NP trapping in non-reperfused renal segments was performed. Serum creatinine was quantified serially over 7 days.
The damaged renal cortico-medullary junction trapped a significant volume of NPs (P = 0.04), which correlated linearly (r = 0.64) with the severity of kidney injury 3 h after reperfusion. Despite global large vessel reperfusion, non-reperfusion in medullary peritubular capillaries was confirmed by MRI and microscopy, indicative of continuing hypoxia due to vascular compromise. Treatment of animals with PPACK NPs after acute kidney injury did not accelerate kidney functional recovery.
Quantification of ischemia-reperfusion injury after acute kidney injury with fluorine MRI/MR spectroscopy of perfluorocarbon NPs objectively depicts the extent and severity of vascular injury and its linear relationship to renal dysfunction. The lack of kidney function improvement after early posttreatment thrombin inhibition confirms the rapid onset of ischemia-reperfusion injury as a consequence of vascular damage and non-reperfusion. The prolongation of medullary ischemia renders cortico-medullary tubular structures susceptible to continued necrosis despite restoration of large vessel flow, which suggests limitations to acute interventions after acute kidney injury, designed to interdict renal tubular damage. Magn Reson Med 79:3144-3153, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
设计一种氟 MRI/MR 光谱方法来量化缺血再灌注损伤后的肾血管损伤，并评估抗凝血酶纳米颗粒（NPs）对保护肾功能的治疗反应。
共 53 只大鼠进行 45 分钟的双侧肾动脉闭塞，在再灌注时分别用普通全氟碳 NPs 或用直接凝血酶抑制剂（PPACK：苯丙氨酸-脯氨酸-精氨酸-氯甲基酮）功能化的 NPs 进行治疗。再灌注后 3 小时，在 4.7T 下进行离体氟 MRI/MR 光谱以量化截留 NPs 的程度和体积，作为血管损伤和缺血再灌注损伤的指标。对未再灌注肾段的结构损伤和 NP 截留进行了微观评估。在 7 天内连续测定血清肌酐。
受损的肾皮质-髓质交界处截留了大量的 NPs（P=0.04），这与再灌注后 3 小时肾脏损伤的严重程度呈线性相关（r=0.64）。尽管大动脉再通，但 MRI 和显微镜证实髓质小管周围毛细血管的非再灌注，表明由于血管损伤导致持续缺氧。急性肾损伤后用 PPACK NPs 治疗动物并不能加速肾功能恢复。
氟 MRI/MR 光谱检测全氟碳 NPs 对急性肾损伤后缺血再灌注损伤的定量分析客观地描绘了血管损伤的程度和严重程度及其与肾功能障碍的线性关系。早期 posttreatment 凝血酶抑制后肾功能无改善证实了缺血再灌注损伤的快速发生是由于血管损伤和非再灌注所致。尽管恢复了大血管血流，但髓质缺血的延长使皮质-髓质管状结构易受持续坏死的影响，这表明急性肾损伤后的急性干预存在局限性，旨在阻断肾小管损伤。磁共振医学 79:3144-3153, 2018. © 2017 国际磁共振学会。
