Prem Priyanka N, Swaminathan Harish, Kurian Gino A
School of Chemical and Biotechnology, SASTRA Deemed University, Tirumalaisamudram, Thanjavur, Tamil Nadu, India.
Vascular Biology Lab, Anusandhan Kendra-1, SASTRA Deemed University, Tirumalaisamudram, Thanjavur, Tamil Nadu, India.
Heliyon. 2025 Jan 2;11(1):e41634. doi: 10.1016/j.heliyon.2025.e41634. eCollection 2025 Jan 15.
Growing evidence indicates that disruptions in mitochondrial quality management contribute to the development of acute kidney injury (AKI), incomplete or maladaptive kidney repair, and chronic kidney disease. However, the temporal dynamics of mitochondrial quality control alterations in relation to renal injury and its recovery remain poorly understood and are addressed in this manuscript.
ology: Male Wistar rats (n = 60) were subjected to varying durations of ischemia and reperfusion. Ischemia was instigated by clamping both renal arteries and for reperfusion, the clamps were removed to restore the blood flow. Renal injury, physiological function, mitochondrial assessment, and cellular mediators were analyzed.
Prolonging ischemia duration reduces bioenergetic function while disrupting the balance of mitochondrial fusion, fission, and mitophagy at the gene expression level while maintaining intact mitochondrial copy number. However, reperfusing a kidney after 45 min of ischemia with varying reperfusion times exacerbates mitochondrial dysfunction and significantly decreases mitochondrial copy number. These declines are particularly evident at 24 h of reperfusion, with some parameters improving by 7 days of reperfusion. Despite these improvements, 7 days of reperfusion did not correlate with renal injury indicators (CrCl- 0.46 ± 0.01, BUN-86.29 ± 4.9, Cr-1.75 ± 0.16) following 45 min of ischemia. Conversely, 15 min of ischemia followed by 7 days of reperfusion restored mitochondrial quality and renal function (CrCl- 7.33 ± 0.59, BUN-43.6 ± 3.16, Cr-0.93 ± 0.14).
The above findings emphasize that mitochondrial quality control alters with the extent of ischemia and subsequent reperfusion time, impacting not only mitochondrial copy number but also the resilience of mitochondria during tissue repair.
越来越多的证据表明，线粒体质量管理的破坏会导致急性肾损伤（AKI）、不完全或不适应性肾修复以及慢性肾病的发生。然而，线粒体质量控制改变与肾损伤及其恢复相关的时间动态仍知之甚少，本手稿对此进行了探讨。
雄性Wistar大鼠（n = 60）接受不同时长的缺血再灌注处理。通过夹闭双侧肾动脉引发缺血，再灌注时松开夹子以恢复血流。分析肾损伤、生理功能、线粒体评估和细胞介质。
延长缺血时间会降低生物能量功能，同时在基因表达水平破坏线粒体融合、裂变和线粒体自噬的平衡，而线粒体拷贝数保持完整。然而，缺血45分钟后不同再灌注时间进行再灌注会加剧线粒体功能障碍，并显著降低线粒体拷贝数。这些下降在再灌注24小时时尤为明显，一些参数在再灌注7天时有所改善。尽管有这些改善，但缺血45分钟后再灌注7天与肾损伤指标（肌酐清除率 - 0.46 ± 0.01，血尿素氮 - 86.29 ± 4.9，肌酐 - 1.75 ± 0.16）并无关联。相反，缺血15分钟后再灌注7天可恢复线粒体质量和肾功能（肌酐清除率 - 7.33 ± 0.59，血尿素氮 - 43.6 ± 3.16，肌酐 - 0.93 ± 0.14）。
上述发现强调，线粒体质量控制随缺血程度和随后的再灌注时间而改变，不仅影响线粒体拷贝数，还影响组织修复过程中线粒体的恢复能力。
