右美托咪定对小鼠视网膜缺血再灌注损伤的影响

Effect of dexmedetomidine on retinal ischemia-reperfusion injury in mice

目的评价右美托咪定对小鼠视网膜缺血再灌注损伤的影响。 方法雄性C57BL/6小鼠48只，8周龄，体重20～24 g，采用随机数字表法分为3组（n＝16）：对照组（C组）、缺血再灌注组（I/R组）和右美托咪定组（D组）。I/R组和D组采用前房灌注法使眼内压升高制备视网膜缺血再灌注损伤模型，缺血60 min，再灌注24 h。分别于缺血前15 min和再灌注前5 min时，D组腹腔注射右美托咪定25 μg/kg，C组和I/R组腹腔注射等容量生理盐水。于再灌注24 h时处死8只小鼠，取视网膜组织，HE染色后光镜下观察病理学结果，采用TUNEL法检测细胞凋亡情况，计算细胞凋亡指数（AI）。于再灌注24 h时处死8只小鼠，取视网膜组织，采用Western blot法检测Bcl-2、Bax、caspase-3及CCAAT增强子结合蛋白同源蛋白（CHOP）的表达水平，计算Bcl-2/Bax比值。 结果与C组比较，I/R组视网膜组织AI升高，Bax、caspase-3和CHOP的表达上调，Bcl-2表达下调，Bcl-2/Bax比值下降（P〈0.05），视网膜组织出现病理学损伤。与I/R组比较，D组视网膜组织AI降低，Bax、caspase-3和CHOP的表达下调，Bcl-2表达上调，Bcl-2/Bax比值升高（P〈0.05），视网膜组织病理学损伤减轻。 结论右美托咪定可减轻小鼠视网膜缺血再灌注损伤，其机制可能与抑制细胞凋亡有关。

Objective To evaluate the effect of dexmedetomidine on retinal ischemia-reperfusion （I/R） injury in mice. Methods Forty-eight C57BL/6 male mice, aged 8 weeks, weighing 20-24 g, were divided into 3 groups （n = 16 each） using a random number table： control group （C group） , I/R group and dexmedetomidine group （D group）. The model of retinal I/R injury was established by elevating intraocular pressure for 60 min using anterior chamber cannulation followed by 24 h of reperfusion. At 15 min before ischemia and 5 rain before reperfusion, dexmedetomidine 25 pLg/kg was intraperitoneally injected in group D, and the equal volume of normal saline was intraperitoneally injected in C and I/R groups. Eight mice were sacrificed at 24 h of reperfusion, and the retina was removed for microscopic examination of path- ologic changes （with light microscope） after haematoxylin and eosin staining and for determination of cell apoptosis in retinal tissues （by TUNEL）. Apoptosis index （AI） was calculated. Eight mice were sacrificed at 24 h of reperfusion, and the retina was removed for determination of the expression of Bcl-2, Bax, caspase-3 and CCAAT/enhancer-binding protein homologous protein （CHOP） in retinal tissues （ by Western blot）. Bcl-2/Bax ratio was calculated. Results Compared with group C, AI was significantly increased, the expression of Bax, caspase-3 and CHOP was up-regulated, the expression of Bcl-2 was down-regula- ted, Bcl-2/Bax ratio was decreased （P〈O. 05）, and pathologic changes were found in retinal tissues in group I/R. Compared with group I/R, AI was significantly decreased, the expression of Bax, caspase-3and EHOP was down-regulated, the expression of Bcl-2 was up-regulated, Bcl-2/Bax ratio was increased （P〈O. 05） , and pathologic changes of retinal tissues were significantly attenuated in group D （P〈O. 05）. Conclusion Dexmedetomidine can reduce retinal I/R injury, and the mechanism may be related to inhibi- ting cell apoptosis in mice.