摘要
目的 探讨lactuside B对脑缺血再灌注损伤大鼠海马和纹状体转录因子CHOP mRNA表达的影响。方法 SD雄性大鼠，280~320 g，随机分为缺血再灌24 h假手术组、模型组、阳性对照组、lactuside B 12.5、25、50 mg·kg-1组和缺血再灌72 h组，共12组，每组4只。采用大鼠大脑中动脉缺血再灌注损伤模型，选取神经缺失症状评分为1~3分的动物入组， 各组动物均按5 mL·kg-1的容积腹腔注射相应的实验药物。大鼠脑缺血2 h， 于再灌注24和72 h后分别处死动物，逆转录聚合酶链反应技术检测大鼠脑海马和纹状体组织不同时间点CHOP mRNA的表达。结果 不同再灌时间的模型组动物神经缺失症状评分增高，与假手术组相比有显著性差异（P<0.01）；用药后阳性对照组和lactuside B各剂量组的神经缺失症状评分均下降，与模型组比较有显著性差异（P<0.01）。另外，结果显示3个剂量组（12.5、25和50 mg·kg-1）的lactuside B均能降低大鼠大脑皮质与海马CHOP mRNA的表达，与模型组比较有显著性差异（P<0.05，P<0.01），其多数剂量组的作用优于阳性对照药尼莫地平（P<0.01）。总体上各组存在较好的量效关系，但只有中剂量组有较好的时效关系。结论 Lactuside B的抗脑缺血作用与其下调大鼠大脑皮质和海马的CHOP mRNA表达有关，有一定的研发价值。
Abstract
OBJECTIVE To investigate the effect of lactuside B on CHOP mRNA expression in rat’s cerebral cortex and hippocampus after cerebral ischemia injury. METHODS Male SD rats of 280-320 g were randomly given brain ischemia-reperfusion treatment for 24 and 72 h respectively and then divided into sham operation group， model group， positive control group， and lactuside B 12.5 mg·kg-1 group， 25 mg·kg-1group and 50 mg·kg-1 group. There were a total of 12 groups with 4 rats in each group. The cerebral ischemia-reperfusion model was established by cerebral artery occlusion for 2 h. The animals with neurological missing symptom scores of 1-3 were selected for the experiment. All the animals were intraperitoneally injected corresponding experimental drugs after reperfusion for 24 and 72 h and then sacrificed. RT-PCR was used to detected the expression of CHOP mRNA in the cerebral and hippocampus at different time. RESULTS After cerebral ischemia-reperfusion injury for 24 and 72 h， the neurological deficits scores of the model group animals were significantly higher compared with the sham group(P<0.01)； the neurological deficit scores of the animals were decreased for positive control group and all lactuside B groups compared with model group(P<0.01). All of the three dosage(12.5，25 and 50 mg·kg-1）of lactuside B could reduce CHOP mRNA expression in cerebral cortex and hippocampus compared with the model group(P<0.05， P<0.01)， and the majority of lactuside B groups were superior to the positive control drug nimodipine(P<0.01). There was a good dose-effect relationship for lactuside B in general， but only the middle dose group showed good time-effect relationship. CONCLUSION The results suggest that the anti-cerebral ischemia effect of lactuside B may be related with the down-regulation of CHOP mRNA expression in cortex and hippocampus. Lactuside B is worthy of development.
关键词
lactuside B /
缺血再灌注损伤 /
大脑皮质 /
海马 /
CHOP /
内质网应激途径 /
凋亡
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Key words
lactuside B /
ischemia-reperfusion injury /
cerebral cortex /
hippocampus /
CHOP /
endoplasmic reticulum system /
apoptosis
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李生莹，詹合琴，闫福林，牛秉轩.
Lactuside B对大鼠脑缺血再灌注损伤后大脑皮质和海马CHOP mRNA表达的影响[J]. 中国药学杂志, 2013, 48(1): 39-42
LI Sheng-ying，ZHAN He-qin，YAN Fu-lin，NIU Bing-xuan.
Effect of Lactuside B on the Expression of CHOP mRNA in Rats′ Cerebral Cortex and Hippocampus after Cerebral Ischemia-Reperfusion Injury[J]. Chinese Pharmaceutical Journal, 2013, 48(1): 39-42
中图分类号：
R965
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脚注
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基金
国家自然科学基金资助项目（81172953）；河南省教育厅自然科学研究项目（2009A310009）
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