In vivo multiphoton imaging of mitochondrial structure and function during acute kidney injury.
In vivo multiphoton imaging of mitochondrial structure and function during acute kidney injury.
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DOI：
10.1038/ki.2012.328
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发表时间：
2013-01
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
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线粒体功能障碍与急性肾缺血和毒性药物损伤的发病机制有关。使用共聚焦显微镜成像细胞线粒体功能的方法已经建立；最近，研究表明，这些技术可以使用多光子显微镜在离体肾脏组织中使用。我们在体内扩展了这种方法，发现在麻醉的啮齿动物中，使用内源性和外源性荧光团的多光子激发可以成像肾脏线粒体的结构和功能。大鼠肾缺血后线粒体烟酰胺腺嘌呤二核苷酸明显升高。静脉注射后，线粒体膜电位依赖性染料TMRM被近端小管占用；缺血后，近端小管的膜电位迅速耗散，线粒体缩短和断裂。相比之下，线粒体膜电位和结构在远端小管中得到了更好的维持。庆大霉素暴露后，线粒体结构、烟酰胺腺嘌呤二核苷酸和膜电位在近端而非远端小管中发生了变化。这些变化是零星的，在动物中高度可变的，并且在非线粒体结构发生变化之前。因此，利用内源性和外源性荧光团的多光子激发，可以实时成像啮齿动物肾脏在缺血-再灌注损伤或药物毒性下线粒体结构和功能的变化。
Mitochondrial dysfunction has been implicated in the pathogenesis of acute kidney injury due to ischemia and toxic drugs. Methods for imaging mitochondrial function in cells using confocal microscopy are well established; more recently, it was shown that these techniques can be utilized in ex vivo kidney tissue using multiphoton microscopy. We extended this approach in vivo and found that kidney mitochondrial structure and function can be imaged in anesthetized rodents using multiphoton excitation of endogenous and exogenous fluorophores. Mitochondrial nicotinamide adenine dinucleotide increased markedly in rat kidneys in response to ischemia. Following intravenous injection, the mitochondrial membrane potential–dependent dye TMRM was taken up by proximal tubules; in response to ischemia, the membrane potential dissipated rapidly and mitochondria became shortened and fragmented in proximal tubules. In contrast, the mitochondrial membrane potential and structure were better maintained in distal tubules. Changes in mitochondrial structure, nicotinamide adenine dinucleotide, and membrane potential were found in the proximal, but not distal, tubules after gentamicin exposure. These changes were sporadic, highly variable among animals, and were preceded by changes in non-mitochondrial structures. Thus, real-time changes in mitochondrial structure and function can be imaged in rodent kidneys in vivo using multiphoton excitation of endogenous and exogenous fluorophores in response to ischemia–reperfusion injury or drug toxicity.
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DOI：
10.1038/jcbfm.2010.9
发表时间：
2010-04
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
通讯作者：
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影响因子：
3.5
作者：
HABERLE, D;WAHLLANDER, A;LACHENMAIER, C
通讯作者：
LACHENMAIER, C
影响因子：
5.5
作者：
DUCHEN, MR;BISCOE, TJ
通讯作者：
BISCOE, TJ
DOI：
10.1152/ajprenal.00443.2004
发表时间：
2005-06-01
影响因子：
4.2
作者：
Feldkamp, T;Kribben, A;Weinberg, JM
通讯作者：
Weinberg, JM
影响因子：
--
作者：
BAGNASCO, S;GOOD, D;BURG, M
通讯作者：
BURG, M