褪黑素对宫内缺血-再灌注胎鼠脑损伤的影响

Effect of melatonin on cerebral injury of fetal rats with intrauterine ischemia reperfusion injury

目的:研究褪黑素(MT)对宫内缺血-再灌注胎鼠脑组织自由基和细胞凋亡的影响。方法:将75只妊娠第19天SD大鼠随机分为对照组(S组)、缺血-再灌注组(I-R组)和MT组,I-R组通过同时钳夹孕鼠双侧子宫、卵巢动脉血供20 min后恢复血供,建立大鼠宫内缺血-再灌注模型;MT组孕鼠在阻断血供的同时腹腔注射MT(10 mg/kg)。分别于再灌注1、6、12、24、48 h剖宫取胎鼠,测定胎鼠脑组织的超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)水平,采用TUNEL法测定胎鼠脑细胞凋亡指数。结果:与S组比较,I-R组1 h SOD、GSH-Px活力下降,6 h MDA含量及脑皮质细胞凋亡指数上升,同时随着再灌注时间的延长,改变趋于明显;与I-R组比较,MT组6 h起SOD、GSH-Px活力均显著升高,12 h起MDA含量和脑细胞凋亡指数均显著下降。结论:腹腔注射MT同步处理对宫内缺血-再灌注胎鼠脑组织有清除自由基、减少细胞凋亡及神经保护的作用。

Objective： To research the effect of melatonin on free radical and apoptosis of cerebral tissue of fetal rats with intrauter- ine ischemia reperfusion injury. Methods： Seventy - five SD rats on the nineteenth day of pregnancy were randomly divided into control group （sham operation, S group）, ischemia- reperfusion group （I -R group） and melatonin group. In I- R group, rat model of intrauter- ine ischemia reperfusion injury was established by clipping bilateral uterine and ovarian arteries for 20 munites simultaneously, and then the blood supply was recovered ; based on the measured taken in I - R group, the pregnant rats in melatonin group were treated with intraperito- neal injection of melatonin （ 10 mg/kg） at the time of blocking blood supply. The fetal rats were obtained at 1,6, 12, 24 and 48 hours after reperfusion. The levels of superoxide dismutase （SOD） , glutathione peroxidase （GSH -Px） and malondialdehyde （MDA） in cerebral tis- sue of fetal rats were detected; TUNEL assay was used to detect apoptotic index of cerebral cells of fetal rats. Results： Compared with S group, SOD and GSH - Px activities at one hour in I - R group decreased, MDA content and apoptotic index of cerebral cortex cells at 6hours increased, the changes became obvious with extension of reperfusion time; compared with I -R group, SOD and GSH -Px activities in melatonin group increased significantly from the sixth hourafter reperfusion, MDA content and apoptotie index of cerebral cortex ceils decreased significantly from the twelfth hour after reperfusion. Conclusion： Intraperitoneal injection of melatonin at the time of blecking blood supply can clear free radical, reduce cell apoptosis and pro- tect nerve pf cerebral tissue in fetal rats with intrauterine ischemia reperfusion injury.