重组人白细胞介素-11对新生大鼠缺氧缺血性脑病的作用

Effect of recombinant human interleukin-11 on hypoxic-ischemic encephalopathy injury in neonatal rats

目的探讨重组人白细胞介素-11(rhIL-11)对新生大鼠缺氧缺血性脑病(HIE)的作用。方法48只7日龄Sprague-Dawley(SD)新生大鼠均分为假手术(Sham)组、HIE组、HIE+0.9μg/kg rhIL-11组及HIE+3.6μg/kg rhIL-11组,每组12只;HIE各组新生大鼠行右颈动脉结扎术后于8%O_(2)和92%N_(2)的低氧气体中缺氧2 h建立HIE模型,Sham组仅暴露右侧颈动脉、不结扎和不缺氧;缺血缺氧造模1 h,各rhIL-11组新生大鼠侧脑室注射rhIL-11,HIE组和Sham组大鼠予等体积生理盐水;造模成功48 h,对4组新生大鼠进行短期行为学测试(翻正反射、负趋地性试验及神经功能缺陷评分);处死新生大鼠取脑组织,测定4组新生大鼠的脑梗死体积和脑组织含水量。结果建立HIE模型48 h后,与HIE组比较,0.9μg/kg rhIL-11组和3.6μg/kg rhIL-11组新生大鼠翻正反射和负趋地性试验时间减少、神经功能缺陷评分降低(P<0.05或P<0.01);与HIE组比较,3.6μg/kg rhIL-11组新生大鼠脑梗死体积减少(P<0.01);脑组织含水量结果表明高剂量rhIL-11减轻脑含水量(P<0.05),与HIE组比较,差异有统计学意义。结论rhIL-11对新生大鼠HIE引起的脑损伤具有神经保护作用。

Objective To investigate the effect of recombinant human interleukin-11(rhIL-11)on hypoxic-ischemic encephalopathy(HIE)injury in neonatal rats.Methods A total of 48 one-week-old Sprague-Dawley(SD)neonatal rats were randomly divided into 4 groups:Sham,HIE,HIE+0.9μg/kg rhIL-11,and HIE+3.6μg/kg rhIL-11 groups(n=12/group).Neonatal rats were given right carotid artery ligation and followed by hypoxia(hypoxic gas of 8%O_(2) and 92%N 2)for 2 h to establish HIE model.The right carotid artery was exposed without ligation and hypoxia in Sham group.At 1 h after HIE modeling,the rhIL-11 groups were injected with rhIL-11 into the lateral ventricle,while HIE and Sham groups were injected with the equal volume of normal saline.At 48 h after HIE modeling,short-term behavioral tests were performed,including righting reflex,negative geotaxis test,and neurological deficit score.After the neonatal rats was sacrificed,their brain tissues were collected to measure the cerebral infarct volumes and brain tissue water contents.Results At 48 h after HIE model establishment,neonatal rats in the 0.9μg/kg rhIL-11 and 3.6μg/kg rhIL-11 groups had reduced time for the righting reflex and negative geotaxis test and decreased neurological deficit scores when compared with HIE group(P<0.05 or P<0.01).Cerebral infarction volumes in the 3.6μg/kg rhIL-11 group were significantly reduced relative to HIE group(P<0.01).Additionally,high-dose rhIL-11 reduced brain tissue water contents when compared with HIE group(P<0.05).Conclusion rhIL-11 may have a neuroprotective effect on neonatal rats with hypoxic-ischemia brain injury.