Institute of Neuroscience, Chongqing Medical University, Chongqing, China, 400016.
J Pharmacol Exp Ther. 2011 Jun;337(3):663-72. doi: 10.1124/jpet.110.177055. Epub 2011 Mar 11.
Subarachnoid hemorrhage (SAH) is a devastating stroke subtype accounting for approximately 3 to 7% of cases each year. Despite its rarity among the various stroke types, SAH is still responsible for approximately 25% of all stroke fatalities. Although various preventative and therapeutic interventions have been explored for potential neuroprotection after SAH, a considerable percentage of patients still experience serious neurologic and/or cognitive impairments as a result of the primary hemorrhage and/or secondary brain damage that occurs. Z-ligustilide (LIG), the primary lipophilic component of the Chinese traditional medicine radix Angelica sinensis, has been shown to reduce ischemic brain injury via antiapoptotic pathways. Accordingly, in our study, we investigated the neuroprotective potential of LIG after experimental SAH in rats. Rats with SAH that was induced using the established double hemorrhage model were studied with and without LIG treatment. Mortality, neurobehavioral evaluation, brain water content, blood-brain barrier (BBB) permeability, and vasospasm assessment of the basilar artery were measured on days 3 and 7 after injury. Additional testing was done to evaluate for apoptosis using TdT-mediated dUTP-biotin nick end labeling staining as well as immunohistochemistry and Western blotting to identify key proapoptotic/survival proteins, i.e., p53, Bax, Bcl-2, and cleaved caspase-3. The results showed that LIG treatment reduced mortality, neurobehavioral deficits, brain edema, BBB permeability, and cerebral vasospasm. In addition, treatment reduced the number of apoptotic cells in the surrounding brain injury site, which accompanied a marked down-regulation of proapoptotic proteins, p53, and cleaved caspase-3. Our data suggest that LIG may be an effective therapeutic modality for SAH victims by altering apoptotic mechanisms.
蛛网膜下腔出血（SAH）是一种破坏性的中风亚型，每年约占 3%至 7%的病例。尽管在各种中风类型中较为罕见，但 SAH 仍然导致约 25%的所有中风死亡。尽管已经探索了各种预防和治疗干预措施来潜在地保护 SAH 后的神经，但相当一部分患者仍然因原发性出血和/或继发性脑损伤而遭受严重的神经和/或认知障碍。Z-当归脂素（LIG）是中药当归的主要亲脂性成分，已被证明通过抗细胞凋亡途径减少缺血性脑损伤。因此，在我们的研究中，我们研究了 LIG 在实验性 SAH 大鼠中的神经保护潜力。使用已建立的双重出血模型诱导 SAH 的大鼠接受和不接受 LIG 治疗。在损伤后第 3 天和第 7 天测量死亡率、神经行为评估、脑含水量、血脑屏障（BBB）通透性和基底动脉血管痉挛评估。进行了额外的测试，使用 TdT 介导的 dUTP-生物素缺口末端标记染色以及免疫组织化学和 Western blot 来评估细胞凋亡，以鉴定关键的促凋亡/存活蛋白，即 p53、Bax、Bcl-2 和 cleaved caspase-3。结果表明，LIG 治疗可降低死亡率、神经行为缺陷、脑水肿、BBB 通透性和脑血管痉挛。此外，治疗还减少了周围脑损伤部位的凋亡细胞数量，同时明显下调了促凋亡蛋白 p53 和 cleaved caspase-3。我们的数据表明，LIG 通过改变细胞凋亡机制可能是 SAH 患者的有效治疗方式。
