ɑ-硫辛酸对缺氧缺血性脑损伤新生大鼠氧化应激水平及脑水肿的影响

Effect of alpha-lipoic acid on oxidative stress and cerebral edema after hypoxic-ischemic brain damage in neonatal rats

目的观察ɑ-硫辛酸(alpha-lipoic acid,ALA)对缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)新生大鼠脑组织氧化应激指标超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-PX)及脑水肿的影响,探讨ɑ-硫辛酸对新生大鼠缺氧缺血性脑损伤的保护作用。方法随机将7日龄Wistar大鼠108只分为3组,假手术组(n=36);缺氧缺血模型组(HIBD,n=36);ALA治疗组(n=36);根据造模后处死时间,各组又分1、3、7 d亚组,每亚组各12只。按RICE法制备新生大鼠HIBD模型。治疗组分别于造模后即开始腹腔注射ALA 100 mg/kg,每天2次,连续5d;假手术组及HIBD模型组于相应时点腹腔注射等量生理盐水。造模后1、3、7 d断头处死取脑,采用干湿质量法测定脑组织含水量,采用比色法检测脑组织匀浆SOD、MDA和GSH-PX的含量。结果 HIBD组与假手术组比较,各时间点脑组织匀浆SOD、GSH-PX降低、MDA升高,脑组织含水量升高(P<0.05)。治疗组与HIBD组比较,各时间点脑组织匀浆GSH-PX回升,脑组织含水量回降(P<0.05)。治疗组与HIBD组比较,造模后1 d时,SOD、MDA差异无统计学意义,造模后3、7 d时,SOD回升,MDA回降(P<0.05)。结论ɑ-硫辛酸对新生大鼠缺氧缺血性脑损伤有保护作用,可减轻缺氧缺血性脑损伤后脑水肿,而其机制之一可能是ɑ-硫辛酸能减轻缺氧缺血所致的脑组织氧化应激损伤。

Objective To investigate the effect of alpha-lipoic acid on oxidative stress and cerebral edema after hypoxic-ischemic brain damage （HIBD）in neonatal rats.Methods A total of 108 neonatal 7-day-old Wistar rats were randomly divided into 3 groups：sham-operated group（sham, n=36）, HIBD group（HIBD, n=36） and alpha-lipoic acid-treated group （treated group, n=36）.Each group was divided into 3 sub-groups （n=12, per sub-group） based on different time points after HIBD （1 d, 3 d, 7 d）.HIBD rat models were established by ligating the left common carotid artery, The sham-operated group and the HIBD group were treated with normal sodium injection intraperitoneally; treated group were treated with alpha-lipoic acid 100 mg/kg every 12 hours in 5 days.Animals were sacrificed at different time points.Changes of brain water content were determined by dry-wet weight method.And the levels of SOD,MDA,GSH-PX were measured.Results HIBD group showed an upward trend in brain water content and the level of MDA after HIBD, were higher than that of sham-operated group at each time point （P〈0.05）.Meanwhile, the levels of SOD and GSH-PX showed the downward trend in HIBD group.The levels of brain water content and the level of MDA in treated group were significantly lower than HIBD group at each time point （ P〈0.05 ） .And the levels of SOD and GSH-PX in treated group were significantly higher than HIBD group at 3 d and 7 d.on the contrary , the level of MDA in treated group was significantly lower than HIBD group at 3 d and 7 d.Conclusion Alpha-lipoic acid can amiliorate cerebral edema, so it can prevent HIBD.The neuronal protective mechanism might be reverse oxidative imbalance in the brain of neonatal rats with HIBD.