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钩藤碱减轻大鼠蛛网膜下腔出血后脑血管痉挛
Rhynchophylline attenuates cerebral vasospasm after subarachnoid hemorrhage in rats
目的 探讨钩藤碱（Rhy）能否减轻大鼠蛛网膜下腔出血（SAH）后的脑血管痉挛（CVS）及其机制。 方法 成年雄性SD大鼠，采用血管内刺破法建立SAH模型。SAH后立即腹腔注射Rhy，24h后通过磁共振成像（MRI）测量基底动脉(BA)直径。BA经HE染色后，测量BA的直径和血管壁厚度；应用Western blotting和免疫荧光染色检测不同组动物BA的磷酸化p38丝裂原活化蛋白激酶（p-p38MAPK）、p-p53和剪切Caspase-3（cleaved-Caspase-3）蛋白的表达水平。结果 MRI和组织学染色结果均表明，10mg/kgRhy在SAH后可明显增加BA的直径并显著减少血管壁厚度（P<0.05）。Rhy明显降低了SAH后BA的p-p38MAPK、p-p53和cleaved-Caspase-3蛋白的表达水平（P<0.05）。Rhy能够明显减少SAH后BA内皮细胞p-p38MAPK、p-p53和cleaved-Caspase-3等凋亡蛋白的表达。结论 Rhy能通过抑制BA内皮细胞凋亡减轻SAH后脑血管痉挛的严重程度。
Objective To investigate the effects of rhynchophylline (Rhy) on alleviating cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). Methods SAH model was established in adult male SD rats by using endovascular perforation method. The Rhy was immediately applied by intraperitoneal injection after SAH. At 24hours after SAH, the diameter and vessel wall thickness of basilar artery (BA) were measured by magnetic resonance imaging (MRI) and/or HE staining. The levels of phosphorylated p38 mitogen-activated protein kinase（p-p38MAPK）, p-p53 and cleaved-Caspase-3 in BA were determined by Western blotting and immunofluorescence. Results After Rhy treatment, the diameter of BA was significantly increased and the thickness of vessel wall was markedly decreased （P<0.05）,Additionally, the levels of p-p38MAPK, p-p53 and cleaved-Caspase-3 in BA were significantly reduced by Rhy treatment after SAH（P<0.05）. Rhy can reduce the expression of BA p-p38 MAPK, p-p53, cleaved-Caspase-3 apoptosis protein in endothelial cell by immunofluorescence compared with SAH+NS group. Conclusion Rhy can attenuate CVS severty after SAH partly through eudothelial cell appotosis via p38MAPK-p53-Caspase-3 pathway.
蛛网膜下腔出血 / 脑血管痉挛 / 基底动脉 / 免疫印迹法 / 免疫荧光 / 大鼠
Subarachnoid hemorrhage / Cerebral vasospasm / Basilar artery / Western blotting / Immunofluorescence / Rat
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