Department of Neurology, The Affiliated Changsha Hospital of Hunan Normal University, Changsha, Hunan, China.
Department of Rehabilitation medicine, The Affiliated Changsha Hospital of Hunan Normal University, Changsha, Hunan, China.
J Surg Res. 2023 Mar;283:1038-1046. doi: 10.1016/j.jss.2022.11.055. Epub 2022 Dec 12.
Little is known about the protective effects of butylphthalide on cerebral ischemia-reperfusion injury. This study aims to investigate the impact on the second mitochondrial-derived activator of Caspases (Smac) and X-linked inhibitor of apoptosis protein (XIAP) expression in the ischemic semidark area using a rat model of carotid artery stenosis.
Thirty Sprague-Dawley rats were randomly divided into the sham-operated group, carotid stenosis model controls, low-dose (20 mg/kg), medium-dose (40 mg/kg), and high-dose (80 mg/kg) butylphthalide groups. The neurological function was scored by the balance beam test (BBT). The morphological changes of brain tissue were detected by Hematoxylin-eosin (HE) staining, with apoptosis detected by Terminal Deoxynucleotidyl Transferase mediated dUTP Nick-End Labeling (TUNEL) staining. Smac and XIAP protein expression were detected by immunohistochemistry (IHC). The expressions of Smac and XIAP mRNA were detected by real-time quantitative polymerase chain reaction (RT-qPCR).
HE showed that neuronal loss, nuclear consolidation, and vacuolar degeneration were significantly reduced in the medium and high-dose butylphthalide groups compared with the model controls. The BBT scores and apoptotic index were significantly lower in the medium and high doses of butylphthalide compared with the model controls. RT-qPCR and IHC showed that Smac, XIAP mRNA and protein expressions in the ischemic hemispheric region were significantly reduced in low, medium, and high doses of butylphthalide compared with the model controls (P < 0.05), showing some concentration effect.
Butylphthalide can significantly reduce Smac and XIAP mRNA and protein expression, inhibit neuronal apoptosis induced by ischemia-reperfusion injury in rats with carotid stenosis, and exert neuroprotective effects.
关于丁基苯酞对脑缺血再灌注损伤的保护作用知之甚少。本研究旨在通过颈动脉狭窄大鼠模型，研究其对缺血半暗区中第二线粒体衍生的半胱天冬酶激活剂（Smac）和 X 连锁凋亡抑制剂蛋白（XIAP）表达的影响。
30 只 Sprague-Dawley 大鼠随机分为假手术组、颈动脉狭窄模型对照组、低剂量（20mg/kg）、中剂量（40mg/kg）和高剂量（80mg/kg）丁基苯酞组。采用平衡梁试验（BBT）对神经功能进行评分。苏木精-伊红（HE）染色检测脑组织形态变化，末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）染色检测细胞凋亡。免疫组织化学（IHC）检测 Smac 和 XIAP 蛋白表达。实时定量聚合酶链反应（RT-qPCR）检测 Smac 和 XIAP mRNA 表达。
HE 染色显示，与模型对照组相比，中、高剂量丁基苯酞组神经元丢失、核固缩和空泡变性明显减轻。与模型对照组相比，中、高剂量丁基苯酞组 BBT 评分和凋亡指数均明显降低。RT-qPCR 和 IHC 显示，与模型对照组相比，低、中、高剂量丁基苯酞组缺血半影区 Smac、XIAPmRNA 及蛋白表达均明显降低（P<0.05），呈一定浓度效应。
丁基苯酞可显著降低大鼠颈动脉狭窄缺血再灌注损伤诱导的 Smac 和 XIAP mRNA 和蛋白表达，发挥神经保护作用。
