Effect of mild hypothermia on expression of cortical Mfn2 during cerebral ischemia-reperfusion in rats

Yanping Zhang, Qian Zhang, Wei Yan, Fei Shi, Gaofeng Zhang, Huai-long Chen
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Abstract

Objective To evaluate the effect of mild hypothermia on the expression of mitofusin 2 (Mfn2) during cerebral ischemia-reperfusion (I/R) in rats. Methods Sixty healthy clean-grade male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 3 groups (n=20 each) using a random number table method: sham operation group (group S), group I/R and mild hypothermia group (group H). In I/R and H groups, cerebral I/R was induced by inserting a nylon thread with rounded tip into the right internal carotid artery which was occluded for 2 h and then released for reperfusion.In group H, the surface cooling was started immediately after removing the nylon thread, and the rectal temperature was maintained at 32-34 ℃ for 3 h. The neurological deficit were assessed and scored at 24 and 48 h of reperfusion.Animals were then sacrificed, the cerebral cortex in ischemic area was then removed for determination of the viable neuron count (by HE staining), apoptotic neurons (by TUNEL), and expression of Mfn2 (by Western blot). Apoptosis rate was calculated. Results Compared with group S, the neurological deficit score and apoptosis rate were significantly increased, and the count of viable neurons was decreased, the expression of Mfn2 was down-regulated at each time of reperfusion in I/R and H groups (P<0.05). Compared with group I/R, the neurological deficit score and apoptosis rate were significantly deereased, and the count of viable neurons was increased, and the expression of Mfn2 was up-regulated at each time of reperfusion in group H (P<0.05). Conclusion The mechanism by which mild hypothermia attenuates cerebral I/R injury may be associated with up-regulating the expression of Mfn2 in cerebral cortex of rats. Key words: Hypothermia, induced; Reperfusion injury; Brain; Mitochondrial proteins
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亚低温对大鼠脑缺血再灌注时皮质Mfn2表达的影响
目的探讨亚低温对大鼠脑缺血再灌注(I/R)过程中丝裂丝蛋白2 (Mfn2)表达的影响。方法8周龄健康洁净级雄性spraguedawley大鼠60只,体重200 ~ 250 g,采用随机数字表法分为假手术组(S组)、I/R组和亚低温组(H组),每组20只。I/R组和H组分别用圆头尼龙线插入右侧颈内动脉,阻断2 H后释放再灌注。H组取下尼龙线后立即开始表面冷却,保持直肠温度32-34℃3 H。在再灌注24、48 H时评估神经功能缺损评分。然后处死动物,取缺血区大脑皮层,测定活神经元数(HE染色)、凋亡神经元(TUNEL)和Mfn2表达(Western blot)。计算细胞凋亡率。结果与S组比较,I/R组和H组大鼠神经功能缺损评分和凋亡率均显著升高,存活神经元数量减少,各再灌注时间Mfn2表达下调(P<0.05)。与I/R组比较,H组大鼠神经功能缺损评分和凋亡率均显著降低,活神经元数量增加,各再灌注期Mfn2表达上调(P<0.05)。结论亚低温减轻脑I/R损伤的机制可能与上调大鼠大脑皮层Mfn2的表达有关。关键词:低温;诱导;再灌注损伤;大脑;线粒体蛋白质
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中华麻醉学杂志
中华麻醉学杂志 Medicine-Anesthesiology and Pain Medicine
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