新生大鼠反复惊厥对皮质区糖皮质激素受体表达的影响

Effects of neonatal recurrent seizures on glucocorticoid receptor expression in the rat brain

目的研究新生期反复惊厥对大鼠大脑皮层内糖皮质激素受体(glucocorticoid receptor,GR)表达的影响。方法生后(postnatal,PN)7d的Sprague-Dawley大鼠48只,随机分成两组,惊厥组每日吸入三氟乙醚诱导惊厥发作1次,每次持续30min,连续6d;对照组同样操作但不吸入三氟乙醚。分别于PN-13d、15d和19d每组各处死8只大鼠,Western blot法和免疫组化法观察大鼠大脑皮层GR表达的变化。结果与对照组相比,在PN-15d时惊厥组大鼠大脑皮层胞浆中GR的表达明显下调(P<0.01),在PN-15d、PN-19d时胞核中GR表达水平明显下调(P<0.05)。与对照组相比较,PN-13d时,惊厥组大鼠顶叶区GR免疫化学累积光密度(AOD)明显降低(P<0.05);PN-15d时,惊厥组大鼠皮层顶叶区GR免疫化学AOD明显降低(P<0.01);PN-19d时,惊厥组大鼠皮层顶叶、颞叶、额叶区GR免疫化学AOD明显降低(P<0.01)。结论新生大鼠反复惊厥造成皮质GR表达的异常,可能参与发育期脑损伤。

Objective To investigate the effets of flurothyl-induced neonatal recurrent seizures on glucocorticoid receptor （ GR ） expression in the rat brain. Methods Forty-eight seven-day-old Sprague-Dawley rats were randomly divided into two groups： control and seizure. Seizures were induced by inhalant flurothyl daily for six consecutive days. Brains were sampled on postnatal days 13, 15 and 19. The expression of GR protein in the cerebral cortex was detected by Western blot and immunohistochemical method. Results The expression of GR in the cerebral cortical plasma protein was significantly lower in the seizure group than in the control group on postnatal clay 15. The expression of GR protein in the cerebral cortical nuclear protein decreased significantly in the seizure group compared with that in the control group on postnatal days 15 and 19 （P 〈0.05）. Compared to the control group, the accumulated optical density （AOD） of GR immunoreactivity （IR） decreased significantly in the parietal cortex on postnatal day 13 （P 〈 0.05 ）, the AOD of GR IR decreased significantly in the parietal cortex and the temporal cortex on postnatal day 15 （P 〈 0.05 ） , and the AOD of GR IR decreased significantly in the parietal cortex, temporal cortex and the frontal cortex in the seizure group on postnatal day 19 （P 〈 0.05 ）. Conclusions Recurrent seizures in neonatal rats result m abnormal GR expression in the cerebral cortex which might play an important role in short-term brain injury induced by early recurrent seizures.