丁基苯酞通过磷酸肌醇3激酶/蛋白激酶B通路对局部脑缺血损伤脑梗死的保护作用

Protective effects of butylphthalide on focal cerebral ischemia injury-induced cerebral infarction through activation of phosphatidylinositol 3 kinase/protein kinase B pathway

目的 观察丁基苯酞对局部脑缺血损伤引起的脑梗死的保护作用。方法 制作大鼠局灶性脑缺血再灌注模型（MCAO）,观察丁基苯酞对脑梗死率的影响,以及与磷酸肌醇3激酶（PI3K）/蛋白激酶B（Akt）通路的关系。结果 丁基苯酞（10、30mg/kg）给药后可以使MCAO大鼠的脑梗死率由41.2%降低至19.7%,神经功能评分由3.8分降低至2.6分,细胞角蛋白（CK）和乳酸脱氢酶（LDH）的水平由5784 U/L和2997 U/L降低至2674 U/L和1615 U/L,并且引起磷酸化Akt（p-Akt）表达增加3倍和半胱氨酰天冬氨酸特异性蛋白酶（Caspase）-3表达降低约3倍。而同时给予PI3K抑制剂LY294002后,可以完全拮抗丁基苯酞引起的MCAO大鼠脑梗死率降低（梗死率由19.8%升高至40.4%）、p-Akt表达的增加和Caspase-3表达的降低。结论 丁基苯酞通过激活PI3K/Akt通路对局部脑缺血损伤引起的脑梗死产生保护作用。

Objective To determine the protective effects and molecular mechanism of butylphthalide on focal cerebral ischemia injury-induced cerebral infarction. Methods The rat focal cerebral ischemia reperfusion model （MCAO） was established. The effect of butylphthalide on the cerebral infarction in rats, and its relationship with phosphatidylinositol 3 kinase （PI3K）/protein kinase B （Akt） path way were investigated. Results MCAO rats cerebral infarction rate were decreased from 41.2% to 19. 7% , nerological score from 3. 8 to 2. 6, cytokeratin （CK） and lactate dehydrogenase （LDH） level from 5 784 U/L and 2 997 U/L to 2 674 U/L and 1 615 U/L after administration of butylphthalide （30 mg/kg）, while the p-Akt expression was increased 3 folds and easpase-3 expression was decreased 3 folds. After given the PI3K inhibitor LY294002, the butylphthalide-induced deduction of cerebral infarction （from 19. 8% to 40.4% ）, the expression of p-Akt and caspase-3 were all antagonized completely. Conclusion Butylphthalide has a protective effect on focal cerebral ischemia injury-induced cerebral infarction by activating the PI3K/Akt pathway.