Department of Anesthesiology of Liaocheng People's Hospital, The Medical College of Qingdao University, Qingdao, Shandong Province, China.
Department of Anesthesiology of Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong Province, China.
J Stroke Cerebrovasc Dis. 2014 Feb;23(2):303-9. doi: 10.1016/j.jstrokecerebrovasdis.2013.02.020. Epub 2013 Mar 27.
Recent research has indicated that mitochondrial adenosine triphosphate-sensitive potassium channels play an important role in cerebral protection, which involves in attenuating the calcium of mitochondria. However, the effect of diazoxide on cerebral ischemia-reperfusion and the role of spermine, the agonist of mitochondrial calcium uniporter (MCU), remain unknown.
We investigated the effect of MCU opener spermine on diazoxide against focal cerebral ischemia-reperfusion injury in rats.
Adult male Wistar rats were randomly divided into 5 groups: the Sham group, the I/R group, the Dzx + I/R group, the Dzx + Sper + I/R group, and the Sper + I/R group. Rats were exposed to 2-hour ischemia and 24-hour reperfusion. Diazoxide were administrated 30 minutes before ischemia, and spermine were given 10 minutes before reperfusion. Rats in the Sham group did not experience the process of ischemia-reperfusion. After 24-hour reperfusion, rats were given neurological performance tests, overdosed with general anesthesia, and then their brains were excised for infarct volume, pathological changes, and biochemical evaluation and analysis.
Rats in the Dzx + I/R group displayed improved neurological deficits and decreased infarct volume and oxidative stress (evidenced by decreased nitric oxide and malondialdehyde but increased antioxidant enzymes [eg, glutathione peroxide and superoxide dismutase]) caused by ischemia-reperfusion. The beneficial effects of diazoxide were significantly attenuated by spermine treatment. Rats in the Sper + I/R group displayed worse neurological deficits, larger infarct volume and more oxidative stress, and less antioxidant enzymes than those in the Dzx + I/R.
Our results suggested that diazoxide, which improved neurological deficits and decreased infarct volume and oxidative stress against ischemia-reperfusion injury, is mediated by spermine.
最近的研究表明，线粒体三磷酸腺苷敏感钾通道在脑保护中发挥重要作用，涉及减少线粒体钙。然而，二氮嗪对脑缺血再灌注的影响以及线粒体钙单向转运体（MCU）激动剂精胺的作用尚不清楚。
研究 MCU 激动剂精胺对二氮嗪治疗大鼠局灶性脑缺血再灌注损伤的影响。
成年雄性 Wistar 大鼠随机分为 5 组：假手术组、缺血再灌注组、Dzx+I/R 组、Dzx+Sper+I/R 组和 Sper+I/R 组。大鼠经历 2 小时缺血和 24 小时再灌注。二氮嗪在缺血前 30 分钟给予，精胺在再灌注前 10 分钟给予。假手术组大鼠不经历缺血再灌注过程。再灌注 24 小时后，对大鼠进行神经功能测试，给予全身麻醉过量，然后取出大脑进行梗死体积、病理变化和生化评估分析。
Dzx+I/R 组大鼠的神经功能缺损改善，梗死体积减小，氧化应激减轻（表现为一氧化氮和丙二醛减少，抗氧化酶[如谷胱甘肽过氧化物酶和超氧化物歧化酶]增加）。精胺处理显著减弱了二氮嗪的有益作用。Sper+I/R 组大鼠的神经功能缺损更严重，梗死体积更大，氧化应激更严重，抗氧化酶更少，均明显劣于 Dzx+I/R 组。
我们的结果表明，二氮嗪通过精胺改善神经功能缺损，减少梗死体积和氧化应激，减轻缺血再灌注损伤。
