孕酮对缺氧缺血性脑损伤新生大鼠血脑屏障通透性及脑水肿的影响

摘要

目的 研究孕酮(PROG)对缺氧缺血性脑损伤(HIBD)新生大鼠血脑屏障(BBB)通透性和脑水肿的作用,并进一步探讨其潜在的机制.方法 7 d龄SD大鼠96只,随机分成4组:正常组、假手术组、缺氧缺血(HI)组和PROG组.建立HIBD动物模型, HI后24 h,伊文思蓝示踪剂检测BBB;干/湿法测定脑含水量;免疫组织化学法观察大脑皮质水孔通道蛋白4(AQP4)表达.结果 正常组和假手术组BBB通透性、脑含水量和脑皮质AQP4的表达差异无显著性(P>0.05);HI组BBB通透性、脑含水量和脑皮质AQP4的表达明显高于假手术组(P<0.01);PROG组BBB通透性、脑含水量和脑皮质AQP4的表达明显低于HI组(P<0.05).结论 PROG通过减轻BBB破坏和脑水肿对HIBD新生大鼠起脑保护作用,PROG的脑保护作用可能与下调新生大鼠脑皮质AQP4的表达有关.%Aim To explore the effects of progesterone ( PROG ) on blood brain barrier( BBB ) permeability and brain edema in newborn rats following hypoxic-ischemic brain damage( HIBD ).and to further investigate its potential mechanisms.Methods Ninety six SD rats( 7-day-old ), were divided randomly into four groups that were normal group, sham operated group,hypoxic-ischemic( HI) group and PROg group.Followed the HIBD of neonatal rat.Rats were executed 24 hours after modeling.BBB permeability was detected by using Evans blue ( EB ) as a labelling compound.The changes of the brain water content( BWC ) were measured by the methods of wet and dry weight.The expression of AQP 4 in cerebral cortex was detected by the immunohistochemistry.Results There was no significant difference of the BBB permeability, BWC and expression of AQP4 between normal group and sham operated group( P ＞ 0.05 ).The BBB permeability,BWC and expression of AQP4 in the HI group were significantly increased compared with those of sham operated group( P＜0.01 ).The BBB permeability,BWC and expression of AQP4 in the PROG group were decreased compared with those of HI group( P ＜0.05 ).Conclusion PROG exerts the neuroprotective effect on HIBD in newborn rats through improving BBB integrity and inhibiting brain edema.which may be associated with down-regulating the expression of AQP4.