目的研究蛇床子素(osthole)在缺血再灌注脑损伤中的脑保护作用。方法实验用SD大鼠55只随机分为假手术组、模型组和三个不同剂量给药组(Ost),其中模型组和给药组采用四血管阻塞法大鼠全脑缺血模型(4VO模型)。各给药组于缺血15min再灌注后1h给予5mg/kg、25mg/kg、125mg/kg蛇床子素腹腔注射治疗。各实验组动物在进行神经功能学评分后,分别用于分析海马CA1区细胞组织形态学变化和caspase3蛋白半定量分析,评价蛇床子素在缺血再灌注脑损伤后的脑保护作用。结果缺血15min再灌注后1h给药的各蛇床子素治疗组大鼠的行为学评分和组织形态学分析结果均明显优于模型组(P〈0.01)并在25mg/kg剂量时表现出最大保护效果,其caspase3表达水平显著降低。结论蛇床子素在脑缺血再灌注脑损伤后有一定的脑保护作用。
Objective To investigate the neuroprotection of osthole against transient global brain ischemia in rat. Methods A total of 55 SD rats were divided randomly into 5 groups: sham operated group (Sham) ; control group (Control) ; osthole 5 mg/kg group (Ost5) ; osthole 25 mg/kg group (Ost25) and osthole 125 mg/kg group (Ost125). The animals in control group and osthole groups were exposed to the modified four-vessel occlusion rat model. After 15 minutes of occlusion and 1 hour of reperfusion, the rats in osthole groups were treated with 5 mg/kg, 25 mg/kg and 125 mg/kg osthole respectively. Twenty-four hours after the reperfusion, neurological deficits were determined by the modified Garcia scoring system. Histopathology (hematoxylin eosin staining) was conducted and five uisnal fields were randomly selected from each section for counting the number of survival cells at CA1 area of hippocampus. The total proteins of hippocampus of the rest animals were taken for analysis of caspase3 protein by using Western blot technique. Results Both the histopathological changes and the neurological deficits scores of osthole groups were better than that of control group ( P 〈 0. 05 ). Results of Western blot indicated that osthole could reduce the elevated level of caspase3 protein induced by the forebrain ischemia and reperfusion. Conclusion Osthole exerts protective effect against injury of global brain ischemia repeffusion.