强啡肽A1-13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

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 U50,488H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к受体激动剂U50,488H（0.5μg,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。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与特异性阿片к受体相结合所产生的加重BIHI的效应。

Changes of dynorphinA1-13 on the treatment of hypoxic-ischemic brain injury by the brain-derived neurotrophic factor in neonatal rats

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 microl (4 x 10(4)/microl) followed by a cerebroventricular microinjection of opioid kappa receptor agonist U50, 488H (0.5 microg, 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 degrees C. 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 group B was seen when compared to group C in the left brain. CONCLUSION: It is suggested that dynorphinA(1 - 13) participates in the pathophysiological process of HIBI. One of the pathways of the beneficial effects of intracerebral transplantation of genetically modified myoblasts producing BDNF on HIBI lies on the inhibition of the function of dynorphin A(1 - 13) through the binding of kappa opioid receptor.