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Hepatic 31 P-magnetic resonance spectroscopy identified the impact of melatonin-pretreated mitochondria in acute liver ischaemia-reperfusion injury.
Journal of Cellular and Molecular Medicine ( IF 4.3 ) Pub Date : 2020-07-21 , DOI: 10.1111/jcmm.15617
Sheung-Fat Ko,Yi-Ling Chen,Pei-Hsun Sung,John Y Chiang,Yi-Ching Chu,Chung-Cheng Huang,Chi-Ruei Huang,Hon-Kan Yip

Acute liver ischaemia‐reperfusion injury (IRI), commonly encountered during liver resection and transplantation surgery, is strongly associated with unfavourable clinical outcome. However, a prompt and accurate diagnosis and the treatment of this entity remain formidable challenges. This study tested the hypothesis that 31P‐magnetic resonance spectroscopy (31P‐MRS) findings could provide reliable living images to accurately identify the degree of acute liver IRI and melatonin‐pretreated mitochondria was an innovative treatment for protecting the liver from IRI in rat. Adult male SD rats were categorized into group 1 (sham‐operated control), group 2 (IRI only) and group 3 (IRI + melatonin [ie mitochondrial donor rat received intraperitoneal administration of melatonin] pretreated mitochondria [10 mg/per rat by portal vein]). By the end of study period at 72 hours, 31P‐MRS showed that, as compared with group 1, the hepatic levels of ATP and NADH were significantly lower in group 2 than in groups 1 and 3, and significantly lower in group 3 than in group 1. The liver protein expressions of mitochondrial‐electron‐transport‐chain complexes and mitochondrial integrity exhibited an identical pattern to 31P‐MRS finding. The protein expressions of oxidative stress, inflammatory, cellular stress signalling and mitochondrial‐damaged biomarkers displayed an opposite finding of 31P‐MRS, whereas the protein expressions of antioxidants were significantly progressively increased from groups 1 to 3. Microscopic findings showed that the fibrotic area/liver injury score and inflammatory and DNA‐damaged biomarkers exhibited an identical pattern of cellular stress signalling. Melatonin‐pretreated mitochondria effectively protected liver against IRI and 31P‐MRS was a reliable tool for measuring the mitochondrial/ATP consumption in living animals.

中文翻译:

肝31 P磁共振波谱确定了褪黑素预处理的线粒体在急性肝缺血再灌注损伤中的作用。

急性肝缺血再灌注损伤(IRI)在肝切除和移植手术中经常发生,与不良的临床结果密切相关。然而,对该实体的迅速,准确的诊断和治疗仍然是巨大的挑战。本研究检验了31 P磁共振波谱(31P‐MRS)的发现可以提供可靠的活体图像,以准确识别急性肝脏IRI的程度,褪黑素预处理的线粒体是保护大鼠肝脏免受IRI侵害的创新方法。成年雄性SD大鼠分为第1组(假手术对照组),第2组(仅IRI)和第3组(IRI +褪黑激素[即,腹膜内给予褪黑激素的线粒体供体大鼠]预处理的线粒体[10 mg /每只大鼠,通过门脉静脉])。到72小时学习期结束时,31P‐MRS显示,与第1组相比,第2组的肝ATP和NADH水平显着低于第1和第3组,第3组的肝水平显着低于第1组。线粒体的肝蛋白表达电子传输链复合物和线粒体完整性表现出与31 P-MRS发现相同的模式。氧化应激,炎症,细胞应激信号和线粒体受损生物标志物的蛋白质表达显示出相反的发现31P‐MRS,而抗氧化剂的蛋白表达从第1组到第3组显着增加。显微镜下的发现表明,纤维化区域/肝脏损伤评分以及炎症和DNA损伤的生物标志物表现出相同的细胞应激信号传导模式。褪黑素预处理的线粒体可有效保护肝脏免受IRI侵害,而31 P-MRS是测量活体动物线粒体/ ATP消耗量的可靠工具。
更新日期:2020-09-28
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