强啡肽A_(1-13)在脑源性神经营养因子治疗新生大鼠缺氧缺血性脑损伤中的变化  

Changes of dynorphinA_ (1-13) on the treatment of hypoxic-ischemic brain injury by the brain-derived neurotrophic factor in neonatal rats

作　　者：洪新如[1] 郑铃[2] 陈新民[1] 

机构地区：[1]南京军区福州总医院儿科,350025 [2]福建医科大学基础医学院微生物学教研室

出　　处：《中华医学杂志》2002年第23期1637-1640,共4页National Medical Journal of China

基　　金：全军"九五"医学科研规划科研基金资助项目 ( 98D0 2 2 )

摘　　要：目的　探讨强啡肽A1 13 在脑内移植脑源性神经营养因子 (BDNF)载体细胞治疗新生大鼠缺氧缺血性脑损伤 (HIBI)中的作用。方法　 7日龄新生大鼠随机分为HIBI +BDNF组 (A)、HIBI +BDNF +U5 0 ,488H组 (B)、单纯HIBI组 (C)和假手术组 (D)。左侧颈总动脉结扎联合低氧吸入形成新生大鼠HIBI,伤后立即脑内植入BDNF载体细胞 (A、B)或空白细胞 (C) ,植入后延髓池内注射阿片κ受体激动剂U5 0 ,488H(0 .5 μg ,B) ,观察处理后 0、1、3d左右侧皮层和海马强啡肽A1 13 免疫活性物质 (ir DynA1 13)含量的变化及处理后 1d脑含水量、丙二醛 (MDA)含量和细胞凋亡情况。结果　左侧皮层ir DynA1 13 含量处理后不同时间A、B或C组显著高于D组 ,1、3dA或B组显著低于C组 ;左侧海马给药后当天 (A、B、C)、1d(B、C)、3d(C)显著高于D组 ,给药 1d(A)、3d(B)显著低于C组。新生大鼠HIBI后 1d ,左脑含水量、MDA和细胞凋亡百分率 ,A、B或C组显著高于D组 ,A组显著低于C组 ;左脑含水量、MDA水平B、C组差别无显著意义 ,左侧脑区细胞凋亡百分率B组显著低于C组。结论　强啡肽A1 13 参与HIBI病理生理过程。植入BDNF载体细胞减轻HIBI的作用途径之一 ,是抑制了强啡肽A1 13 与其特异性阿片κ受体相结合所产生的加重BIHI的效应。Objective To explore changes and role of dynorphinA 1-13 on the experimental treatment of hypoxic-ischemic brain injury (HIBI) by intracerebral transplantation of genetically modified myoblasts expressing and secreting brain-derived neurotrophic factor (BDNF) in neonatal rats. Methods Seven-day-old Sprague-Dawley rats were randomly divided into HIBI+BDNF group (A), HIBI+BDNF+U50,488H group (B), HIBI group (C) and sham-operated group (D). Pups were intracerebroparenchymally transplanted with either genetically modified myoblasts producing and secreting BDNF (A, B) or their parent cells (C) at 0.8 μl (4×104/μl) followed by a cerebroventricular microinjection of opioid κ receptor agonist U50,488H (0.5 μg, B) or vehicles (A, C) shortly after HIBI undergone by a permanent ligation of left common carotid artery followed by a 2.5 h inhalation of humidified 8%O 2+92%N 2 at 37℃. Water contents of the brain, levels of malondiadehye (MDA) and cell apoptosis were investigated 1 d after the procedure. Contents of dynorphinA 1-13-like immunoreactivity (ir-DynA 1-13) at the left and right cortex and hippocampus were tested by radioimmunoassay 0, 1, 3 d postinjury. Results Levels of ir-DynA 1-13 in left cortex were markedly increased in group A, B or C when compared to group D different times after the procedure and markedly decreased in group A or B vs group C 1, 3 d after the procedure. Levels of ir-DynA 1-13 in left hippocampus were also markedly increased in group A, B and C (0 d), B, C (1 d) and C (3 d) when compared to group D and markedly decreased in group A (1 d) and B (3 d) vs group C, respectively. Water contents, MDA levels and percentage of cell apoptosis were significantly higher in group A, B or C than those in group D and these parameters were obviously lowered in group A compared to group C in the left brain 1 d after the procedure. There were no significant differences of water contents and levels of MDA between group B and C but significantly lowered percentage of cell apoptosis in g

关 键 词：新生儿 动物实验 作用机理 缺氧缺血性脑损伤 强啡肽A1-13 脑源性神经营养因子 治疗 

分 类 号：R722.12[医药卫生—儿科] R965[医药卫生—临床医学]