新生大鼠缺氧缺血性脑病脑组织氨基酸含量变化及脑活素的治疗作用

AMINO ACIDS IN BRAIN OF NEWBORN RATS WITH HYPOXIC- ISCHEMIC ENCEPHALOPATHY AND THERAPEUTIC ACTION OF CEREBROLYSIN

本文旨在研究脑组织中氨基酸含量与新生大鼠缺氧缺血性脑病(HIE)发病机制的关系及脑活素的治疗机制,在建立新生大鼠HIE模型的基础上,采用氨基酸自动分析仪检测103例大鼠左侧顶叶脑组织氨基酸含量,并研究脑组织病理改变,同时通过侧脑室及肌肉两种途径给予脑活素(2.5mL·kg^(-1))治疗,每日一次,观察72h。结果显①HIE组脑组织兴奋性氨基酸(EAA)(谷氨酸、天门冬氨酸)含量明显增高,P<0.01,以缺氧缺血后48h EAA含量最高;②脑活素治疗组在侧脑室及肌肉注射脑活素治疗48h时,EAA含量均明显低于同期各HIE对照组,差异显著,P<0.01。与正常对照组比较,治疗后24h及48h存在差异(P<0.01),治疗72h后差异无显著意义(P>0.01)。③侧脑室及肌肉注射脑活素后24h,两组脑组织中EAA含量差异无显著意义(P>0.05);48h后,两组出现差异,P<0.05。结论①脑组织兴奋性氨基酸含量异常升高与缺氧缺血性脑病的发病机制有一定关系。②脑活素治疗HIE的机制可能与其显著降低脑组织中EAA含量有关。③侧脑室注射脑活素和肌肉注射脑活素的治疗效果存在一定的差异。

To study the relationship between excitatory amino acid concentration in brain tissues of newborn rats and the pathogenesis of hypoxic-ischemic encephalopathy and cerebrolysin therapy, morphological and metabolic effects of the left cerebrum ischemia due to permanent left carotid arteries ligation and short-term systemic hypoxia in fifty newborn rats served as means of imitating the hypoxic ischemic encephalopathy of neonates were investigated. Immediately afterwards Cerebrolysin was administered, either by intracerebroventricular infusin (i.c.v) or by intramuscular injection. Moreover, we also studied the effect of Cerebrolysin (EBEWE, Austria) in acute brain hypoxiaischemia. Results showed by using Amino Acid Analyzer, we it was found that EAA concentration in brain tissues increased at different time after hypoxia-ischemia. Glutamate concentration in HIE groups was(mg·g-1): 11.12(24 h), 18.62(48 h), 12.64(72 h); Aspartic acid(mg·g-1): 11.56(24 h), 15.44(48 h), 10.74(72 h) . Hypoxia-Ischemia led to increase of EAA concentration in control rats at any of the chosen time( P < 0.01) . Groups of Cerebrolysin treatment for 48 h(2.5 mL· kg-1 body mass) decreased the content of EAA significantly. There was observed no difference of EAA concentration in both i.c.v groups and i.m groups in the first 24 h of the experiment ( P > 0.05) , but after the treatment for 48 h, there was observed a certain degree of variety between the two groups(P < 0.01) . 9m conclusions: (1) Abnormality of EAA concentration in brain tissue is associated with pathogenesis of newborn rats HIE. (2) Cerebrolysin is effective in protecting brain cells from further damage through its influence on cerebral EAA concentration. (3) There exists a certain degree of difference between the daily intracere-broventricular(i.c.v) and daily intramuscular(i.m) drug administration.