摘要
目的 探讨 β 内啡肽及阿片 μ受体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低氧缺血性脑损伤 (HIBI)中的作用。方法 7d龄新生大鼠随机分为HIBI+BDNF组 (A)、HIBI +BDNF +DAMGO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 μ受体激动剂DAMGO (0 2 μg ,B) ,观察处理后 0、 1、 3d左侧皮层和海马 β 内啡肽免疫活性物质 (ir β ΕΡ)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 (1)ir β ΕΡ含量 ,左侧皮层A组显著低于C组 (0d) ,B、C组显著高于D组 (0、 1d) ,海马A、B、C组均显著高于D组 (0d) ,C组显著高于A组或D组 (1d)。 (2 )左脑含水量C组显著高于A、B或D组 ,MDA水平A、B、C组均显著高于D组 ,A组显著低于B或C组。 (3)细胞凋亡百分率 ,左侧皮层B、C组显著高于D组 ,C组显著高于A或B组 ,A组显著低于B组 ;海马A、B、C组显著高于D组 ,A组显著低于C组。结论 β 内啡肽参与HIBI病理生理过程。脑内植入BDNF载体细胞影响HIBI的作用环节之一 ,是抑制了 β 内啡肽与其特异性阿片
Objective To explore the role of β endorphin and opioid μ receptor 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+DAMGO group (B),HIBI group (C)and sham operated group(D).Pups were transplanted unilaterally intracerebroparenchymally with either genetically modified myoblasts producing and secreting BDNF(A,B)or their parent cells(C)at 0 8 μl(4×10 4/μl)followed by a cerebroventricular microinjection of opioid μ receptor agonist DAMGO(0 2μg,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 β endorphin like immunoreactivity (ir β ΕΡ) at the left cortex and hippocampus were tested by radioimmunoassay 0?1?3d thereafter.Rusults (1)Levels of ir β EP were significantly lower in group A than in C(0d),higher in group B or C vs D(0,1d)in the left cortex,markedly higher in A,B or C when compared to D(0d)and higher in group C than in group A or D(1d)in the left hippocampus.(2)Contents of water were significantky elevated in group C compared to A,B or D and levels of MDA were statistically higher in group A,B or C vs D,lower in group A than in group B or C in the left hemisphere.(3)Percentages of neural apoptosis were significantly increased in group B or C compared to D,decreased in group C vs A or B and decreased in group A vs B in the left cortex.They were obviously increased in group A,B or C than in group D and decreased in group A than in group C in the left hemisphere.Conclusion β endorphin has been suggested to participate int the pathophysiological process of HIBI.One of benficial effects of intracerebral transplantation of genetically modified myoblasts producing BDNF on HIBI lies in the inhibition of the function of β endorphin through its specific binding of its optimal μ opioid receptor.
出处
《中华急诊医学杂志》
CAS
CSCD
2002年第5期318-320,330,共4页
Chinese Journal of Emergency Medicine
基金
解放军全军"九.五"医学科研规划科研基金资助项目 (98D0 2 2 )
