左旋四氢巴马汀对大鼠局灶性脑缺血再灌注损伤后神经元凋亡和Caspase-3表达的影响  

Effects of L-tetrahydropalmatine on Neuronal Apoptosis and the Expression of Caspase-3 Protein after Focal Cerebral Ischemia Reperfusion Injure in Rats

作　　者：马小亚[1] 谭婷[1] 武冬梅[2] 王美纳[1] 梁维薇[1] 王玉虎[1] 王娜[1] 

机构地区：[1]西安交通大学医学院第二附属医院,陕西西安710004 [2]西安市儿童医院,陕西西安710003

出　　处：《现代中药研究与实践》2011年第4期33-36,共4页Research and Practice on Chinese Medicines

基　　金：陕西省科学技术研究发展计划项目(2008k13-02(2))

摘　　要：目的探讨左旋四氢巴马汀(L-THP)对大鼠局灶性脑缺血再灌注损伤神经元凋亡和半胱氨酸蛋白酶-3(Caspase-3)表达的影响。方法实验大鼠随机分为4组,即假手术组、模型组、L-THP高、低剂量组(40、20 mg kg-1 d-1)。采用线栓法阻塞大脑中动脉建立大鼠局灶性脑缺血再灌注模型,于缺血1h再灌注6、24、48 h时进行神经行为缺陷评分,并应用原位末端标记(TUNEL)法和免疫组织化学法分别检测缺血皮质区的神经元凋亡与Caspase-3蛋白的表达。结果脑缺血再灌注6 h即出现神经元凋亡和Caspase-3的表达,随着再灌注时间的延长逐渐增加,至24 h达高峰,48 h逐渐减少。Caspase-3蛋白表达与神经元凋亡的时相动态变化趋势基本一致。与模型组比较,不同剂量的L-THP均能不同程度的减少在各时相的TUNEL阳性神经元数量(P<0.05),减低Caspase-3蛋白表达(P<0.01),降低神经行为评分(P<0.05)。结论 L-THP可能通过抑制Caspase-3蛋白的表达,减少神经元凋亡,发挥对脑缺血再灌注损伤的保护作用。Objective To explore the effects of 1-tetrahydropalmatine （ L-THP ） on neuronal apoptosis and the expression of Caspase-3 in cerebral cortex after transient focal cerebral ischemia reperfusion injure in rats. Methods The experimental rats were randomly divided into 4 groups： sham group, model group, L-THP high dose group （ 40 mg·kg^-1·d^-1 ） and L-THP low dose group （ 20 mg·kg^-1·d^-1 ） . Transient focal cerebral ischemia reperfusion model of rats＇ middle cerebral artery occlusion（MCAO） was induced by inserting a nylon filament through left internal carotid artery. After 1 h MCAO the nylon filament was withdrawn to allow reperfusion. At 6, 24, 48 h of reperfusion, neurological deficit was scored, neurons apoptosis in ischemic cerebral cortex was characterized by terminal deoxynucleotide transferase mediated uridine 5＇-triphosphate-biotin nick end-labeling（TUNEL） staining. The expression of Caspase-3 was determined by immunohistochemistry method. Results TUNEL positive neurons and the expression of Caspase-3 appeared at 6 h after reperfusion and increased gradually, it reached at peak value at 24 h and reduced gradually at 48 h. The time phase of Caspase-3 protein expression was consistent with that of neuronal apoptosis. Compared with model group at each time point of the reperfusion, in L-THP high dose group and L-THP low dose group , TUNEL positive neurons were markedly decreased （P 〈 0.05） , the expression of Caspase-3 were significantly lower （P 〈 0.01） and neurological deficit scores were significantly reduced（P 〈 0.05）. Conclusion L-THP protects neurons from ischemis-reperfusion mediated damage by inhibiting the expression of Caspase-3 protein and decreasing neuronal apoptosis.

关 键 词：左旋四氢巴马汀 脑缺血再灌注损伤 神经元凋亡 CASPASE-3 

分 类 号：R285.5[医药卫生—中药学]