辛伐他汀对大鼠蛛网膜下腔出血后脑内微血栓形成的影响

Impact of simvastatin on microthrombosis in cortical after subarachnoid hemorrhage in rats and its mechanism

目的观察辛伐他汀对大鼠蛛网膜下腔出血（SAH）后脑内微血栓形成的影响，并对其可能机制作初步探讨。方法24只成年健康雄性sD大鼠，用数字随机分为对照组、SAH组、安慰剂组、辛伐他汀组，经大鼠自体尾动脉（股动脉）非肝素化动脉血注入视交叉池致蛛网膜下腔出血模型。腹腔注射辛伐他汀，注射剂量20mg·kg-1·d-1。在蛛网膜下腔出血7d后处死大鼠，并取脑组织标本，HE染色测定微血凝块，通过免疫染色测定纤维蛋白（原）测定微血栓形成。结果对照组脑组织中，微血栓形成为每个视野（1±1）个，SAH组和安慰剂组中分别为（25±5）个和（24±4）个，辛伐他汀组为（5±2）个。和对照组相比SAH组微血栓数显著增多（P〈0．01），和安慰剂组相比辛伐他汀组微血栓数明显减少（P〈0．01），SAH组和安慰剂组比较差异无统计学意义（P〉0．05）。结论辛伐他汀在大鼠视交叉池注血的蛛网膜下腔出血模型中能够减轻脑皮质内的微血栓的形成。

Objective Accumulating evidence demonstrates that subarachnoid hemorrhage （SAH）- induced microthrombosis plays important roles in the pathogenesis of delayed cerebral ischemia. The purpose of the present study was to determine the impact of simvastatin on microthrombi formation and cerebral vasospasm after SAH and explore its mechanism. Methods A total of 24 adult male SD rats were divided into 4 groups ： （ l ） control group （ n = 6 ） ; （2） SAH group （ n = 6） ; （ 3 ） SAH ＋ vehicle group （ n = 6） and （4） SAH ＋ simvastatin group （ n = 6 ）. SAH was induced by injecting 0. 3 ml of fresh arterial, non- heparinized blood into prechiasmatic cistern in 20 sec with a syringe pump. In the SAH ＋ simvastatin group, simvastatin was administered ip at a dose of 20 mg ~ kg-X ~ d- ~ after SAH. Brain samples were excised after perfusion fixation at 7 days post-SAH. Microclots were evaluated by H＆E staining. Microthrombi formation was measured by fibrinogen immunostaining. Results The number of microthrombi was 1 ＋ 1,25 ~ 5, 24 ~ 4 and 5 ~ 2 in control, SAIl, vehicle and simvastatin groups respectively. The number of microthrombi significantly increased in cerebral cortex at 7 days post-SAH （P 〈 0. 01 ）. The treatment of simvastatin down- regulated the formation of microclots in the SAH model and the number of microthrombi decreased significantly in the SAH ＋ simvastatin group as compared with the SAH or SAH ＋ vehicle groups （ P 〈 0. 01 ）. Conclnsion The administration of simvastatin alleviates microthrombosis in late phase of SAH in this precbiasmatic blood injection model.