摘要
目的探讨c-Jun氨基末端激酶(c-Jun N-terminal kinas,JNK)信号通路在急性一氧化碳中毒迟发性脑病中的作用。方法 120只雄性SD大鼠随机分成空白对照组(BC组)、急性一氧化碳中毒迟发性脑病组(CO组)和JNK抑制剂SP600125组(SP组)3组,每组40只,采用静态吸入式染毒法复制急性一氧化碳中毒迟发性脑病大鼠模型,选取染毒后1、3、7、14、28 d为时相点,应用Morris水迷宫试验检测平均潜伏期等学习记忆能力,免疫组化法检测海马区p-JNK表达,Tunel法检测海马区锥体细胞凋亡。结果 CO组大鼠平均潜伏期较BC组明显延长(P<0.01),SP组较CO组明显缩短(P<0.01),但仍比BC组延长(P<0.01);p-JNK在CO组大鼠海马区表达较BC组明显增强(P<0.01),SP组较CO组表达明显减弱(P<0.01),较BC组明显增强(P<0.01);CO组海马区锥体细胞第3天已经有凋亡增多(9.94%±1.22%),第7和14天增多最明显(39.77%±1.91%,29.72%±4.89%),第28天仍然增多(5.88%±0.55%),凋亡指数与BC组相比有明显增高(P<0.01),而SP组凋亡指数与CO组相比明显降低(P<0.01)。结论 JNK信号通路参与了急性一氧化碳中毒迟发性脑病的发生,应用其特异性抑制剂SP600125阻断其转导可减少海马区神经元的凋亡,减轻急性CO中毒对学习记忆能力的损害。
Objective To study the effect of c-Jun N-terminal kinas（JNK） signaling pathway on delayed encephalopathy after acute carbon monoxide poisoning.Methods One hundred and twenty male SD rats were randomly divided into 3 groups with forty rats in each group： blank control group（BC group）,delayed encephalopathy after acute carbon monoxide poisoning group（CO group） and the JNK inhibitor SP600125 group（SP group）.The animal model was established by static inhaled exposure method.The animals were evaluated at 1st,3rd,7th,14th and 28th day after acute carbon monoxide poisoning.Morris water maze test was used to measure the learning ability and memory including the average latency.The expression of p-JNK in hippocampal area was measured by immunohistochemistry.The apoptosis of pyramidal neurons in the hippocampal gyrus area was measured by in situ apoptosis detection.Results In Morris water maze test,the average latency in CO group and SP group was longer compared with BC group whereas the average latency in SP group was shorter compared with CO group（P0.01）.The expression of p-JNK in in CO group was significantly increased compared with BC group（P0.01） whereas the expression of p-JNK in SP group was decreased compare with CO group.The apoptosis of pyramidal neurons in the hippocampal gyrus CA1 area started to increase at 3rd day after the CO exposure（9.94%±1.22%）,and reached the peak at 7th and 14th day（39.77%±1.91%,29.72%±4.89%）,and persisted at 28th days but at a lesser extent（5.88%±0.55%）.The apoptotic index in CO group was increased significantly compared with BC group（P0.01） whereas the apoptotic index was significantly decreased in SP group compare with CO group（P0.01）.Conclusions JNK signaling pathway may be involved in delayed encephalopathy after acute carbon monoxide poisoning and SP600125 can reduce the apoptosis of neurons in the hippocampal gyrus area and reduce acute carbon monoxide poisoning-induced the learning and memory defects by blocking the JNK signaling pathway.
出处
《中国神经精神疾病杂志》
CAS
CSCD
北大核心
2010年第6期344-347,共4页
Chinese Journal of Nervous and Mental Diseases
