a－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

摘要

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.%目的：观察a－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a－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 a－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a－硫辛酸能减轻缺氧缺血所致的脑组织氧化应激损伤。