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

Effect of Lactuside B on the Expression of CHOP mRNA in Rats′ Cerebral Cortex and Hippocampus after Cerebral Ischemia-Reperfusion Injury

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。

OBJECTIVE To investigate the effect of lactuside B on CHOP mRNA expression in rat＇ s cerebral cortex and hippo- campus 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-lgroup 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 bippocampns 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.