Blood brain barrier (BBB) disruption plays an important role in brain injury after acute kidney injury (AKI). However, its underlying mechanisms remain poorly understood. Recent evidence has revealed that proper mitochondrial function is essential for BBB permeability. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a key factor in mitochondrial biogenesis and function. This study was designed to investigate the role of PGC-1α in BBB injury after AKI and its related mechanisms. Mice received recombinant adenovirus encoding murine PGC-1α (100 μl, 1.0 × 109PFU/ml) or vehicle 5 days before renal I/R or sham operation. Twenty-four hours after the operation, brain, kidney and serum samples were collected for assessments. We found that mice suffering from renal I/R injury showed decreased PGC-1α levels in both the kidney and BBB. PGC-1α transfection resulted in increased PGC-1α level and mitochondrial transcripts in BBB at 24 h after AKI. PGC-1α transfection improved renal function, systemic inflammation and BBB permeability via both the paracellular and transcellular pathways. Further study suggested that PGC-1α overexpression elevated fatty acid oxidation related gene expression. Our findings demonstrate the importance of PGC-1α in AKI-induced BBB injury and suggest that it could be a therapeutic target for BBB repair via the regulation of mitochondrial function.

中文翻译：

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PGC-1α对急性肾脏损伤后血脑屏障的保护作用。

血脑屏障（BBB）破坏在急性肾损伤（AKI）后的脑损伤中起重要作用。但是，其基本机制仍然知之甚少。最近的证据表明，适当的线粒体功能对于血脑屏障通透性至关重要。过氧化物酶体增殖物激活受体γcoactivator-1α（PGC-1α）是线粒体生物发生和功能的关键因素。本研究旨在探讨PGC-1α在AKI术后BBB损伤中的作用及其相关机制。在肾I / R或假手术前5天，小鼠接受了编码鼠PGC-1α（100μl，1.0×109PFU / ml）或载体的重组腺病毒。手术后二十四小时，收集脑，肾和血清样本进行评估。我们发现患有肾脏I / R损伤的小鼠在肾脏和BBB中均显示PGC-1α水平降低。在AKI后24小时，PGC-1α转染导致BBB中PGC-1α水平和线粒体转录物增加。PGC-1α转染通过细胞旁和跨细胞途径改善了肾功能，全身炎症和血脑屏障通透性。进一步的研究表明，PGC-1α过表达提高了脂肪酸氧化相关基因的表达。我们的发现证明了PGC-1α在AKI诱导的BBB损伤中的重要性，并暗示它可能是通过调节线粒体功能来修复BBB的治疗靶标。进一步的研究表明，PGC-1α过表达提高了脂肪酸氧化相关基因的表达。我们的发现证明了PGC-1α在AKI诱导的BBB损伤中的重要性，并暗示它可能是通过调节线粒体功能来修复BBB的治疗靶标。进一步的研究表明，PGC-1α过表达提高了脂肪酸氧化相关基因的表达。我们的发现证明了PGC-1α在AKI诱导的BBB损伤中的重要性，并暗示它可能是通过调节线粒体功能来修复BBB的治疗靶标。