EUK-134对缺氧缺血性脑损伤的保护作用  

Neuroprotection of EUK-134 in brain injury from hypoxia and ischemia

作　　者：廖红[1] 陈易[1] 倪新莉[1] 

机构地区：[1]宁夏医科大学总医院麻醉科,银川市750004

出　　处：《临床麻醉学杂志》2011年第12期1217-1219,共3页Journal of Clinical Anesthesiology

基　　金：留学人员科技活动项目择优资助(宁人社函[2009]317号)

摘　　要：目的探讨EUK-134对新生猪缺氧缺血性脑损伤的保护作用。方法出生3～7d的雄性猪,体重2.0～3.0kg,采用缺氧40min窒息7min后心肺复苏的方法制备缺氧缺血性脑损伤模型,取自主循环恢复(ROSC)的新生猪20头随机均分为EUK-134治疗组(E组)和对照组(C组),另取6头作为假手术组(S组)。ROSC后30min,E组静脉注射EUK-1342.5mg/kg,随后静脉输注1.25mg·kg-1·h-1,输注时间3.5h;C组以低温磷酸缓冲液(PBS)替代EUK-134。分别于ROSC后24、48、72、96h行神经行为学评分(NDS评分)。于ROSC后第4天取左脑进行HE染色,光镜下观察病理学特征,并计算纹状体存活神经元密度;取右脑行免疫组化染色观察壳状核细胞DNA氧化损伤产物8-羟基脱氧鸟苷(8-OHdG)表达情况,计算累积光密度值。结果 E组脑缺血性损害较C组减轻。与S组比较,E、C组脑纹状体存活神经元密度降低,壳状核8-OHdG生成明显增多,NDS评分升高(P<0.01)。与C组比较,E组脑组织存活神经元密度明显增加,壳状核存活神经元密度明显升高,尾状核损伤不及壳状核严重,存活神经元密度明显增加;E组8-OHdG生成明显低于C组(P<0.01),但仍高于S组(P<0.05)。结论 EUK-134能够减轻新生猪脑纹状体神经元缺血性损伤,机制可能与抑制了DNA的氧化有关。Objective To test the hypothesis that treatment with antioxidants EUK-134 （an SOD and catalase mimetic） protects striatal neurons from hypoxia and ischemia （HI）. Methods Male piglets were randomly divided into 2 groups （n =10 each）. The hypoxia-ischemia was induced by hypoxia 40 rain and asphyxia 7 min followed by cardiopulmonary resuscitation. Piglets received PBS （group C） or EUK-134 （2.5 mg/kg, then 1.25 mg. kg-1. h-1 for 3.5 h, group E） 30 min after resuscitation. Other 6 piglets were selected into Sham group（group S）. Neurobehavioral assessments were evaluated at 24, 48, 72 and 96 h after ROSC. Brain was removed at 4 days of recovery. Histology feature in left striatum was analyzed in HE staining. 8-OHdG immunohistochemistry in right putamen was also analyzed. Results EUK-134 reduced the neuronal damage induced by HI. The density of viable neurons in putamen in group C was （11±5）%. Treatment with EUK-134 increased viability to （45 ± 16）% （P〈0.01L In caudate nucleus, injury was less severe than in putamen, neuronal viability was increased from （56±11） % in in group C to （83±29）% in group E. Neurological deficit scores were improved on the early stage of recovery with EUK-134 treatment. The production of 8-OHdG was significantly higher in group C than in group E or group S. Conclusion EUK-134 can alleviate neurons ischemic injury in striatum of newborn pigs. The mechanism is related to DNA oxidative damage inhibition.

关 键 词：缺氧缺血性脑损伤 神经保护 EUK-134 

分 类 号：R722.1[医药卫生—儿科]