Detrimental effects of transient cerebral ischemia on middle cerebral artery mitochondria in female rats.
Detrimental effects of transient cerebral ischemia on middle cerebral artery mitochondria in female rats.
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短暂性脑缺血对雌性大鼠大脑中动脉线粒体的有害影响。
DOI：
10.1152/ajpheart.00346.2022
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Busija,DavidW
中科院分区：
文献类型：
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作者：
Rutkai,Ibolya;Merdzo,Ivan;Wunnava,Sanjay;McNulty,Catherine;Chandra,ParthaK;Katakam,PrasadV;Busija,DavidW
在生理条件下，年轻的雄性和雌性大鼠脑血管中的线粒体数量和动态是不同的，但这些差异是如何受到中风的影响尚不清楚。在男性中，我们发现短暂性大脑中动脉闭塞（tMCAO）后，大大脑中动脉（MCAs）的线粒体数量增加，可能是由于线粒体分裂。然而，中风对雌性大鼠MCAs的线粒体影响尚未研究。为了解决这一差异，我们使用电子显微镜、Western blot、线粒体呼吸和Ca2+sparks活性测量对雌性、naïve或假Sprague-Dawley大鼠的MCAs进行了形态学、生化和功能研究，在tMCAO 90分钟前和90分钟后48小时。双方线粒体特征及线粒体与肌浆网（SR）的关系均出现不利变化。然而，线粒体和线粒体/SR关联通常在正常外观的范围内。线粒体蛋白水平在同侧（ipsi）和对侧（contra）之间相似。非呼吸耗氧量、最大呼吸量和备用呼吸量在ipsi组和对照组之间相似，但与假手术组相比有所降低。基础呼吸、质子泄漏和ATP产生在MCAs中相似。暴露于线粒体atp敏感钾通道开启剂：二氮氧化物的假性和ipsi MCAs中Ca2+火花活性增加。我们的研究结果表明，tMCAO对MCAs内的线粒体有正向和反向的影响。雌性大鼠脑动脉对tMCAO的线粒体反应与先前在雄性大鼠中看到的反应有很大不同，这表明需要特定的基于性别的治疗。我们认为，男性和女性线粒体特征的差异，包括线粒体形态、呼吸和钙火花活动，导致了短暂性缺血再灌注反应中保护和修复机制的性别差异。
Mitochondrial numbers and dynamics in brain blood vessels differ between young male and female rats under physiological conditions, but how these differences are affected by stroke is unclear. In males, we found that mitochondrial numbers, possibly due to mitochondrial fission, in large middle cerebral arteries (MCAs) increased following transient middle cerebral artery occlusion (tMCAO). However, mitochondrial effects of stroke on MCAs of female rats have not been studied. To address this disparity, we conducted morphological, biochemical, and functional studies using electron microscopy, Western blot, mitochondrial respiration, and Ca2+sparks activity measurements in MCAs of female, naïve or sham Sprague–Dawley rats before and 48 h after 90 min of tMCAO. Adverse changes in mitochondrial characteristics and the relationship between mitochondria and sarcoplasmic reticulum (SR) in MCAs were present on both sides. However, mitochondria and mitochondrial/SR associations were often within the range of normal appearance. Mitochondrial protein levels were similar between ipsilateral (ipsi) and contralateral (contra) sides. Nonrespiratory oxygen consumption, maximal respiration, and spare respiratory capacity were similar between ipsi and contra but were reduced compared with sham. Basal respiration, proton leak, and ATP production were similar among MCAs. Ca2+sparks activity increased in sham and ipsi MCAs exposed to a mitochondrial ATP-sensitive potassium channel opener: diazoxide. Our results show that tMCAO has effects on mitochondria in MCAs on both the ipsi and contra sides. Mitochondrial responses of cerebral arteries to tMCAO in females are substantially different from responses seen previously in male rats suggesting the need for specific sex-based therapies.NEW & NOTEWORTHYWe propose that differences in mitochondrial characteristics of males and females, including mitochondrial morphology, respiration, and calcium sparks activity contribute to sex differences in protective and repair mechanisms in response to transient ischemia-reperfusion.