灯盏乙素乙酯对大鼠大脑中动脉结扎所致局灶性脑缺血的保护作用及机制研究

Protective effect and mechanism of scutellarin ethyl ester on focal cerebral ischemia induced by ligation of middle cerebral artery in rats

观察灯盏乙素乙酯对大鼠大脑中动脉结扎所致局灶性脑缺血的保护作用,并探讨其作用机制。该实验选用SPF级雄性SD大鼠84只,随机分为7组:假手术组、模型组、阳性药组(尼莫地平组12 mg·kg^(-1))、灯盏花素片组(48 mg·kg^(-1))、灯盏乙素乙酯高、中、低剂量组(100,50,25 mg·kg^(-1))。采用线栓法制备大鼠大脑中动脉结扎(MCAO)模型,观察大鼠MCAO时神经功能状态,TTC染色法测脑梗死面积,半自动生化分析仪测定血清中MDA,SOD,NO的变化。分别采用200 mg·L^(-1)OxLDL和100μg·L^(-1)TNF-α作用人脐静脉内皮细胞(HUVECs)24 h,建立Ox-LDL和TNF-α细胞损伤模型,测定细胞上清液中MDA,SOD,NO,ET,6-keto-PGF_(1α),TXB_2,IL^(-1),IL-6,IL-8,ICAM-1和PECAM-1水平。结果显示,灯盏乙素乙酯能有效改善MCAO大鼠神经功能,明显减小脑梗死面积。与模型组比较,血清中SOD和NO活性提高,MDA含量降低;细胞上清液中SOD,6-keto-PGF_(1α)和NO活性提高,IL^(-1),IL-6,IL-8,ICAM-1,PECAM-1,TXB_2,ET和MDA含量降低。结果表明,灯盏乙素乙酯对大鼠大脑中动脉结扎所致局灶性脑缺血具有一定的保护作用,其作用机制可能与抗氧化应激,改善血管内皮细胞功能及减轻炎性反应有密切关系。

To observe the protective effect of scutellarin ethyl ester on focal cerebral ischemia injury induced by middle cerebral artery occlusion in rats（MCAOR）,and explore its mechanism.Totally 84 male SD rats were randomly divided into seven groups：shamoperated group,model group,positive drug group（niomdipine,12 mg·kg^-1）,Brevisapin tablets group（48 mg·kg^-1）,and high,middle and low-dose scutellarin ethyl ester groups（100,50,25 mg·kg^-1）.The MCAOR model was prepared by using thread embolism method to observe the neurological function of rats,the area of cerebral infarction was measured with TTC,and the levels of MDA,SOD and NO in serum were detected with semiautomatic biochemistry analyzer.Ox-LDL and TNF-α cell injury models was established by treating HUVECs with 200 mg·L^-1ox-LDL and 100 μg·L^-1TNF-α,and the levels of MDA,SOD,NO,ET,6-keto-PGF1αTXB2,IL-1,IL-6,IL-8,ICAM-1 and PECAM-1 in the cell supernatant were determined.The results showed that scutellarin ethyl ester could effectively improve the neurological function of MCAOR rats,and significantly reduce the area of cerebral infarction.Compared with the model group,activities of SOD and NO in serum increased,while content of MDA decreased.In the cell supernatant,activities of SOD,6-keto-PGF1αnd NO increased,content of IL-1,IL-6,IL-8,ICAM-1,PECAM-1,TXB2,ET and MDA decreased,which indicated that scutellarin ethyl ester has a certain protective effect on focal cerebral ischemia injury induced by middle cerebral artery occlusion in rats,and its mechanism may be related to antioxidative stress,improvement of endothelial function and reduction in inflammatory reaction.