AG490对大鼠脑液压冲击伤后脑水肿及水通道蛋白4表达的影响

Experimental study of effect of AG490 on cerebral edema and expression of AQP-4 following controlled cortical impact injury in rats

目的研究AG490对大鼠脑液压冲击伤后继发性脑水肿及水通道蛋白4(AQP-4)表达的影响。方法取健康成年雄性SD大鼠104只,按照随机数字表法分为假手术组8只,对照组48只,AG490组48只,对照组及AG490组随机各分为6个亚组分别对应伤后各时间点3h、6h、12h、24h、48h、72h。对照组及AG490组给予液压冲击打击,制作大脑损伤模型;假手术组仅给予颅骨钻孔术不给予液压冲击。AG490组于伤后1小时按照5mg/kg给予腹腔注射AG490,对照组接受等量生理盐水。干湿重法测定脑组织含水量,免疫组织化学法测定脑组织AQP-4蛋白的表达,HE染色后光镜下观察细胞形态学改变。结果 (1)和假手术组比,对照组及AG490组脑组织含水量均升高(P<0.05)。AG490组各时间段均比对照组脑组织含水量少(P<0.05)。(2)AQP-4表达阳性细胞镜下呈棕黄色空泡状。AG490组各时间亚组AQP-4表达水平均较对照组减低(P<0.05)。(3)光镜下见AG490组各时间点均较对照组病理损伤轻。结论脑损伤后急性期应用AG490可以明显减轻创伤后脑水肿,其作用可能与抑制AQP-4在损伤脑组织中的表达有关。

Objective To research the effects of AG490 on the cerebral edema and the expression of AQP-4 in the injured rats.Methods 104 health adult male SD rats were randomly divided into the sham-operated group（n=8）,control group（n=48）,and AG490 group（n=48）.Control group and AG490 group was randomly divided into six sub-groups according to each time point 1h,6h,12h,24h,48h,72h.The rats in the control group and AG490 group were given fluid percussion hit to produce brain injury model.The rats in the sham-operated group were only given sphenotresia.The rats in the AG490 group received injection of AG490 according to the dose of 5mg/kg by intraperitoneal at 3 hours after injury,while the control group received the same dose of normal saline.Brain water content was measured by the wet and dry weight methods.Immunohistochemistry was used to determine the expression of AQP-4 protein in brain tissue and morphological changes were observed under light microscope after HE staining.Results（1）The water content of brain tissue of rats in the control group and AG490 group increased compared with the rats of sham-operated group（P〈0.05）.The brain water content of rats in the AG490 group at different time sub-group were lower than that in the control group（P〈0.05）.（2）AQP-4 positive cells was showed brown vacuoles under microscope.AQP-4 expression levels of AG490 group at different time sub-group were lower than that of the control group.（3） Pathological damage of brain tissue of rats in AG490 group at all time points compared with the control group was light under microscope.ConclusionAG490 used in the acute phase of brain injury can obviously alleviate edema volume,which may be related with inhibiting the expression of AQP-4 protein.