Abstract: Objective:To investigate the protective effect of butylphthalide on the brain of the rats with acute ischemic stroke, and to elucidate its mechanism in the treatment of acute ischemic stroke. Methods:Forty-eight rats were randomly divided into sham operation group, model group (focal cerebral ischemia rat model) and butylphthalide group (focal cerebral ischemia rat model + butylphthalide treatment), with 16 rats in each group.The nerve symptom scores of the rats in various groups were determined, and the brain tissue was stained by HE staining; triphenyl four azole nitrogen chloride (TTC) was used to detect the percentage of cerebral infarction area; Western blotting method and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the expression levels of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinases-9 (MMP-9), and nuclear transcription factor inhibiting protein kappa B alpha(IκBα), nuclear transcription factor kappa B (NF-κB) p65(NF-κB p65) protein and mRNA in the brain tissue of the rats. Results:In sham operation group, there were no infarction and neurological defect in the brain tissue. Compared with model group, the percentage of cerebral infarction area and the neurological function score of the rats in butylphthalide group were significantly decreased(P<0.01). The structure and distribution of brain tissue cells of the rats in sham operation group were intact and uniform; most of the cells in model group were necrotic, cytoplasmic rupture, nucleus rupture and condensation; a small number of brain cells in butylphthalide group were swollen and necrotic. Compared with sham operation group, the expression levels of HGF, VEGF, MMP-2, MMP-9, and NF-κB p65 protein and mRNA in the brain tissue of the rats in model group were significantly decreased (P<0.01), and the expression levels of IκBα protein and mRNA were significantly increased (P<0.01). Compared with model group, the expression levels of HGF, VEGF, MMP-2, MMP-9, and NF-κB p65 protein and mRNA in the brain tissue of the rats in butylphthalide group were significantly increased (P<0.01),and the expression levels of IκBα protein and mRNA were significantly decreased (P<0.01). Conclusion:Butylphthalide can improve the nerve function of the rats with acute ischemic stroke and reduce the area of cerebral infarction;its mechanism may be related to increasing the HGF level in the brain tissue and promoting the cerebral angiogenesis.

Key words: butylphthalide, ischemic stroke, hepatocyte growth factor, vascular endothelial growth factor, matrix metalloproteinase-2, matrix metalloproteinase-9, nuclear transcriptron factor-kappaB