布洛芬对新生大鼠缺氧缺血后脑损伤的保护作用

Neuroprotective role of ibuprofen in hypoxic-ischemic brain damage in neonatal rats

目的探讨布洛芬对新生大鼠缺氧缺血性脑损伤(HIBD)的保护作用及其机制。方法 7日龄Wistar大鼠40只,随机分成生理盐水组、布洛芬组、HI+生理盐水组、HI+布洛芬组。HI+生理盐水组和HI+布洛芬组结扎左侧颈总动脉,吸入氧氮混合气体50 min制作成HIBD模型;HI+布洛芬组在HI后2 h给予布洛芬皮下注射100 mg/kg,然后予布洛芬50 mg/(kg.d)皮下注射,持续6 d;布洛芬组在HI+布洛芬组同时间给予布洛芬。在HI后7 d处死大鼠,取脑作免疫组化染色,进行脑灰质[微管相关蛋白(MAP-2)]、脑白质[髓鞘碱性蛋白(MBP)和神经丝(NF)]损伤的判断,并在每张切片的Cortex、DG、CA区计数β-半乳糖苷结合凝集素(galectin-3)阳性细胞。结果生理盐水和布洛芬组大鼠大脑灰质均正常,未出现梗死灶;脑白质MBP和NF无损失。HI+布洛芬组大脑梗死面积(33.18±4.57)mm2,体积(39.18±4.29)mm3;HI+生理盐水组分别为(35.23±4.15)mm2、(40.23±4.65)mm3,两组差异无统计学意义(t=34.54、42.38,P均>0.05)。HI+生理盐水组脑白质MBP损失为(42.32±7.56)%,NF为(40.34±6.83)%;HI+布洛芬组分别为(31.34±5.67)%、(30.82±5.24)%,两组差异有统计学意义(t=13.51、11.56,P均<0.05)。HI+布洛芬组Cortex区的galectin-3细胞较HI+生理盐水组明显下降,差异有统计学意义(U=11.52,P<0.05)。结论布洛芬对HI后大脑的白质有明显保护作用,可能与降低小胶质细胞活性有关;但对大脑灰质无明显保护作用。

Objective To investigate neuroprotective effect of ibuprofen on neonatal rats brain damage after hypoxia-ischemia（HI）.Methods Fourty 7-day-old mice were divided to normal saline（NS） group,ibuprofen group,HI＋NS group,and HI＋ibuprofen group.The HI＋NS group and HI＋ibuprofen group subjected to unilateral ligation of the left common carotid artery（ischemia） and 50 min of hypoxia for set up HI model.An initial dose of ibuprofen 100mg/kg was administered 2 hours after HI followed by a maintenance dose 50mg/kg every 24 hours for 6 days in HI＋ibuprofen group and ibupreofen group.The mice were sacrificed 7 days after HI.The grey matter,microtubule-associated protein-2（MAP-2） and white matter,myeline basic protein（MBP） and neurofilameng（NF） injury were detected by immunohistochemical staining.The number of galectin-3 positive cells were counted in Cortex,DG,CA area.Results In NS group and ibuprofen group,the grey matter was normal and does not appear infarct.In HI＋ibuprofen group,the infarct area was（33.18±4.57） mm2 and the infarct volume was（39.18±4.29） mm3.In HI＋NS group,the infarct area was（35.23±4.15） mm2 and the infarct volume was（40.23±4.65） mm3.There was no difference between two groups（t=34.54,42.38,P0.05）.In HI＋ibuprofen group,the loss of MBP was（42.32±7.56）% and the loss of neurofilament（NF） was（40.34±6.83）%.In HI＋NS group,the loss of MBP was（31.34±5.67）% and the loss of NF was（30.82±5.24）%.There were significant differences between two groups（t=13.51,11.56,P0.05）.The number of galectin-3 positive cells in Cortex were significantly lower in HI＋ibuprofen group than that in HI＋NS group（U=11.52,P0.05）.Conclusions Ibuprofen has a protective effect on brain white matter injury,which may be through decreasing microglial activation.However,ibuprofen has no protective effect on gray matter injury.