缺血再灌注大鼠脑保护过程中蛋白激酶C同工酶抑制剂的作用(英文)

Reaction of isoenzyme inhibitor of protein kinase C during cerebral protective process in ischemic reperfusion rat

背景:蛋白激酶C(ProteinKinaseC,PKC)抑制剂能明显减轻缺血性脑损害,但其毒副作用大、价格昂贵。灯盏花素注射液能明显抑制PKC活性,对缺血性脑损害有一定的保护作用。目的:研究局灶脑缺血再灌注大鼠PKC抑制剂灯盏花素缺血脑保护作用的可能机制。设计:完全随机设计,对照实验研究。主要观察指标:采用线栓法制备大鼠局灶脑缺血再灌注模型。于缺血1.5h再灌注4,24,72h观察PKC同工酶γ蛋白表达及神经元凋亡的变化规律。结果:再灌注4hPKCγ及神经元凋亡明显升高,PKCγ在24h达高峰,72h开始下降(P<0.05);神经元凋亡的变化规律同PKCγ(P<0.01);灯盏花素组再灌注24h前能明显抑制PKCγ及神经元凋亡的表达(P>0.05)。结论:灯盏花素的缺血脑保护作用可能与其下调PKCγ蛋白表达有关。

BACKGROUND:Protein kinase C(PKC) inhibitor can significantly relieve the ischemic cerebral damage;however,it has huge toxic side effects and dear costs.Erigreron breviscapus(EB) injection can significantly inhibit PKC activity,which has certain protective reaction to ischemic cerebral damage. OBJECTIVE:To study the possible mechanism of the protective reactions of EB,a PKC inhibitor,in focal cerebral ischemic reperfusion rat. DESIGN:A completely randomized controlled study. MAIN OUTCOME MEASURES:Focal cerebral ischemic reperfusion rat model was established with thread ligation method.The expression of PKC isoenzyme γprotein and the changing regulations of apoptosis of neurons were observed at 1.5 hours after ischemia and at 4,24 and 72 hours after reperfusion. RESULTS:The expression of PKC γprotein and the apoptosis of neurons significantly increased at 4 hours after reperfusion and PKC γhit its peak at 24 hours and started to decrease at 72 hours(P< 0.05).The changing regulation of neuron apoptosis was as same as PKC γ(P< 0.01).In EB group, the expression of PKC γand the apoptosis of neuron were significantly inhibited before 24 hours after reperfusion(P< 0.05). CONCLUSION:The cerebral protective reaction in ischemic brain of EB may relate with its adjustment in the expression of PKC γprotein.