Corridon Peter R
Department of Immunology and Physiology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates.
Healthcare Engineering Innovation Center, Khalifa University, Abu Dhabi, United Arab Emirates.
Front Physiol. 2023 Feb 8;14:1024238. doi: 10.3389/fphys.2023.1024238. eCollection 2023.
Hydrodynamic fluid delivery has shown promise in influencing renal function in disease models. This technique provided pre-conditioned protection in acute injury models by upregulating the mitochondrial adaptation, while hydrodynamic injections of saline alone have improved microvascular perfusion. Accordingly, hydrodynamic mitochondrial gene delivery was applied to investigate the ability to halt progressive or persistent renal function impairment following episodes of ischemia-reperfusion injuries known to induce acute kidney injury (AKI). The rate of transgene expression was approximately 33% and 30% in rats with prerenal AKI that received treatments 1 (T) and 24 (T) hours after the injury was established, respectively. The resulting mitochondrial adaptation exogenous IDH2 (isocitrate dehydrogenase 2 (NADP+) and mitochondrial) significantly blunted the effects of injury within 24 h of administration: decreased serum creatinine (≈60%, < 0.05 at T; ≈50%, < 0.05 at T) and blood urea nitrogen (≈50%, < 0.05 at T; ≈35%, < 0.05 at T) levels, and increased urine output (≈40%, < 0.05 at T; ≈26%, < 0.05 at T) and mitochondrial membrane potential, Δψ, (≈ by a factor of 13, < 0.001 at T; ≈ by a factor of 11, < 0.001 at T), despite elevated histology injury score (26%, < 0.05 at T1; 47%, < 0.05 at T). Therefore, this study identifies an approach that can boost recovery and halt the progression of AKI at its inception.
在疾病模型中，流体动力学流体输送已显示出影响肾功能的前景。该技术通过上调线粒体适应性，在急性损伤模型中提供预处理保护，而单独的流体动力学注射生理盐水可改善微血管灌注。因此，应用流体动力学线粒体基因输送来研究在已知会诱发急性肾损伤（AKI）的缺血再灌注损伤发作后，阻止进行性或持续性肾功能损害的能力。在肾前性AKI大鼠中，分别在损伤确立后1小时（T1）和24小时（T24）接受治疗，转基因表达率分别约为33%和30%。由此产生的线粒体适应性——外源性异柠檬酸脱氢酶2（NADP+）（线粒体）在给药后24小时内显著减轻了损伤的影响：血清肌酐水平降低（≈60%，T1时P<0.05；≈50%，T24时P<0.05）和血尿素氮水平降低（≈50%，T1时P<0.05；≈35%，T24时P<0.05），尿量增加（≈40%，T1时P<0.05；≈26%，T24时P<0.05）以及线粒体膜电位Δψ增加（≈增加13倍，T1时P<0.001；≈增加11倍，T24时P<0.001），尽管组织学损伤评分升高（T1时为26%，P<0.05；T24时为47%，P<0.05）。因此，本研究确定了一种可以促进恢复并在AKI发病初期阻止其进展的方法。
