Neuroprotection of Osthole against Cerebral Ischemia/Reperfusion Injury through an Anti-apoptotic Pathway in Rats
Neuroprotection of Osthole against Cerebral Ischemia/Reperfusion Injury through an Anti-apoptotic Pathway in Rats
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DOI：
10.1248/bpb.b15-00699
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发表时间：
2016-03-01
影响因子：
2
通讯作者：
Zhang, Ming
中科院分区：
文献类型：
--
作者：
Li, Kang;Ding, Dun;Zhang, Ming
脑缺血再灌注（I/R）损伤是急性脑损伤的主要原因。I/R损伤的发病机制包括细胞凋亡、炎症和氧化应激。据报道，植物香豆素化合物蛇蛇素对大鼠局灶性脑I/ r损伤有保护作用。然而，其机制尚不清楚。本研究假设蛇床子素在大鼠局灶性脑I/R损伤中通过抑制细胞凋亡起作用。我们采用大脑中动脉闭塞（MCAO）诱导脑I/R损伤2h后再灌注。我们将60只大鼠随机分为三组（每组20只）：假手术、载药处理I/R和蛇孔处理I/R。在大鼠脑缺血前30分钟腹腔注射蛇床子素（40 mg/kg）或载药。再灌注24小时后，我们采集脑梗死体积、脑含水量、组织学变化、末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸镍端标记（TUNEL）染色以及裂解caspase-3、bax和bcl-2水平。蛇床子素治疗可显著减轻I/R损伤所致的脑功能障碍和组织学损害。此外，蛇床子碱处理大鼠的凋亡神经元细胞显著减少，bax和cleaved caspase-3也明显减少。bcl-2水平升高。蛇床子素治疗通过抑制细胞凋亡保护大脑免受脑I/R损伤。因此，蛇床子可能是预防脑I/R损伤的一种新的实用策略。
Cerebral ischemia/reperfusion (I/R) injury is a major cause of acute brain injury. The pathogenetic mechanisms underlying I/R injury involve apoptosis, inflammation and oxidative stress. Osthole a plant coumarin compound has been reported to protect against focal cerebral I/R-induced injury in rats. However, the mechanism remains unknown. Here we hypothesize that osthole acts through inhibition of apoptosis during focal cerebral I/R injury in rats. We induced cerebral I/R injury by middle cerebral artery occlusion (MCAO) for 2h followed by reperfusion. We randomly assigned 60 rats to three groups (20 rats per group): sham-operated, vehicle-treated I/R, and osthole-treated I/R. We treated rats intraperitoneally with osthole (40 mg/kg) or vehicle 30 min before cerebral ischemia. We harvested the brains for infarct volume, brain water content, histological changes and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining as well as cleaved caspase-3, bax, and bcl-2 levels 24 h after reperfusion. Osthole treatment significantly attenuated cerebral dysfunction and histologic damage induced by I/R injury. Moreover, osthole-treated rats had a dramatic decrease in apoptotic neuronal cells along with a decrease in bax and cleaved caspase-3. The bcl-2 levels increased. Osthole treatment protects the brain from cerebral I/R injury by suppressing cell apoptosis. Thus, osthole may represent a novel practical strategy to prevent cerebral I/R injury.