丁苯酞软胶囊对缺血再灌注大鼠脑损伤的保护作用

Protective effect of butylphthalide soft capsule on cerebral ischemia-reperfusion injury in rats

目的:探讨丁苯酞软胶囊对缺血再灌注大鼠脑损伤的保护作用。方法:将40只雄性SD大鼠随机分为假手术组、缺血再灌注组、丁苯酞软胶囊低剂量组和丁苯酞软胶囊高剂量组,每组10只。除假手术组外,其余3组均采用拴线法建立大鼠大脑中动脉局灶缺血再灌注损伤模型。术后24h评估各组大鼠神经行为变化及大鼠脑梗死体积,检测超氧化物岐化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)、含半胱氨酸的天冬氨酸蛋白水解酶3(Caspase3)、Caspase8及Caspase9活性和丙二醛(MDA)含量,ELISA法检测肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)和IL-6含量,Westernblotting检测核因子-κB(NF-κB)信号通路相关蛋白的表达。结果:与假手术组比较,缺血再灌注组大鼠神经行为评分提高(P<0.01),脑梗死体积增加(P<0.01),MDA、TNF-α、IL-1β及IL-6含量增加(P<0.01),Caspase3、Caspase8及Caspase9活性上升(P<0.01),Bcl-2表达量下调(P<0.01),Bax、p-IκBα及p-NF-κBp65表达量上调(P<0.01)。与缺血再灌注组比较,丁苯酞软胶囊低、高剂量组大鼠神经行为评分降低(P<0.01),脑梗死体积减少(P<0.01),MDA、TNF-α、IL-1β及IL-6含量降低(P<0.01),Caspase3,Caspase8及Caspase9活性下降(P<0.01),Bcl-2表达量上调(P<0.01),Bax、p-IκBα及p-NF-κBp65表达量下调(P<0.01)。结论:丁苯酞软胶囊能显著的抑制缺血再灌注大鼠脑损伤,与阻断NF-κB信号通路有关。

Objective: To explore the protective effect of butylphthalide soft capsule (BSC) on cerebral ischemia-reperfusion injury (CIRI) in rats. Methods: Forty SD rats were randomly divided into sham group,ischemia-reperfusion group,and low-dose and high-dose of BSC groups.Except for the sham group,the rat model of CIRI was established by ligation of middle cerebral artery.After 24 hours of the operation,neurological behavior score,cerebral infarction volume,and the contents of malondialdehyde (MDA),tumor necrosis factor alpha (TNF-α),interleukin (IL)-1β,IL-6,superoxide dismutase (SOD),glutathione peroxidase (GSH-Px),catalase (CAT),cysteine aspartic acid protease 3 (Caspase 3),Caspase 8,Caspase 9,and the expression of nuclear factor-κ-gene binding κ(NF-κB) signal pathway related protein were detected. Results: Compared with sham group,the neurological behavior score,cerebral infarction volume,the contents of MDA,TNF-α,IL-1β,IL-6,Caspase 3,Caspase 8 and Caspase 9,and the expression levels of Bax,p-IκBα and p-NF-κB p65 were increased,while the activities of SOD,CAT and GSH-Px as well as the expression level of Bcl-2 was decreased in ischemia-reperfusion group ( P <0.01).All these effects were reversed by low- or high-dose of BSC treatment ( P <0.01). Conclusion: BSC could inhibit CIRI in rats,and the mechanisms might be related to blocking the signal pathway of NF-κB.