灯盏花素对局灶性脑缺血大鼠海马神经元损伤及Akt/JNK3/caspase-3通路的影响

Effects of Breviscapine on Hippocampal Neuronal Injury and Akt/JNK3/caspase-3 Pathway in Rats with Focal Cerebral Ischemia

目的:探讨灯盏花素对局灶性脑缺血大鼠海马神经元损伤及Akt/JNK3/caspase-3通路的影响。方法:SD大鼠100只根据体质量随机分成对照组、模型组和灯盏花素低(10.0 mg·kg-1)、中(20.0 mg·kg-1)、高(40.0 mg·kg-1)剂量组,模型组、灯盏花素各剂量组构建局灶性脑缺血模型,灯盏花素各剂量组于造模成功开始给予相应剂量药物灌胃,对照组和模型组给予等体积生理盐水。试验结束后,对大鼠认知功能进行评价;测定大鼠海马组织Akt、JNK3、caspase-3的mRNA、蛋白水平。结果:与模型组比较,灯盏花素各剂量逃避潜伏期降低,经过原平台位置的次数、原平台象限留的时间升高(P<0.05),且呈剂量依赖性(P<0.05);但仍未恢复到对照组的水平(P<0.05)。与对照组比较,模型组、灯盏花素各剂量组Akt mRNA及蛋白表达水平降低,JNK3、caspase-3mRNA及蛋白表达水平升高(P<0.05);且灯盏花素各剂量组Akt mRNA、蛋白表达水平高于模型组,JNK3、caspase-3 mRNA、蛋白表达水平低于模型组(P<0.05),均呈剂量依赖性(P<0.05)。结论:灯盏花素对大鼠脑局灶性脑缺血大鼠海马神经元损伤具有较好的保护作用,能明显改善其神经功能、感觉及运动功能,其机制与灯盏花素能促进Akt mRNA、蛋白的表达,抑制JNK3、caspase-3 mRNA、蛋白的表达,进而抑制海马神经元细胞凋亡有关。

Objective: To investigate the effects of breviscapine on hippocampal neuronal injury and Akt/JNK3/caspase-3 pathway in rats with focal cerebral ischemia. Methods: Totally 100 SD rats were randomly divided into 5 groups according to the body weight:the control group,the model group,and breviscapine low( 10.0 mg·kg-1),medium( 20.0 mg·kg-1) and high( 40 mg·kg-1) dose groups. All the rats except for those in the control group were made into focal cerebral ischemia models and received the corresponding treatments. At the end of the experiment,the cognitive function of rats was evaluated;the mRNA and protein expression levels of Akt,JNK3 and caspase-3 in rat’s hippocampus were determined. Results: Compared with that in the model group,the escape latency of breviscapine groups was decreased,the time of the original platform quadrant and the number of original platform positions were increased( P<0.05),which were all in a dosage-dependent manner( P < 0.05). However,the indices in breviscapine groups were all poorer than those in the control group( P<0.05). Compared with those in the control group,Akt mRNA and protein expression levels were decreased,and JNK3,caspase-3 mRNA and protein expression levels were increased in the model group and breviscapine groups( P<0.05). Compared with those in the model group,Akt mRNA and protein expression levels were increased,and JNK3,caspase-3 mRNA and protein expression levels were decreased( P<0.05) in a dose-dependent manner in breviscapine groups( P< 0.05). Conclusion: Breviscapine has a good protective effect on hippocampal neuronal injury in rats with focal cerebral ischemia,and can significantly ameliorate its neurological function,sensory and motor function. The mechanism is related to the protein expression promotion of Akt mRNA and the protein expression inhibition of JNK3 and caspase-3 mRNA by breviscapine resulting in the apoptosis inhibition of hippocampal neurons.