Wang Zhong, Chen Gang, Zhu Wei-Wei, Bian Jie-Yong, Shen Xiao-Ou, Zhou Dai
Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
Ann Clin Lab Sci. 2010 Winter;40(1):32-42.
Although previous studies indicate that simvastatin can attenuate cerebral vasospasm after subarachnoid hemorrhage (SAH), its effect on the secondary pathophysiological changes after SAH has not been investigated. Accumulating evidence demonstrates that SAH-induced microthrombosis plays important roles in the pathogenesis of delayed cerebral ischemia. To date, however, no study focused on the treatment of microthrombosis in SAH models. The purpose of this study was to determine the impact of simvastatin on microthrombi formation after SAH in rats. Adult male SD rats were divided into four groups: (1) 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 the 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/d after SAH. Brain samples were excised after perfusion fixation at 7 days after SAH. The cross-sectional areas of the middle cerebral artery and anterior cerebral artery were measured. Microclots were evaluated by H&E staining. Microthrombi formation was measured by fibrin(ogen) immunostaining. The results showed that administration of simvastatin prevented vasospasm on day 7 following SAH (p <0.01). The number of microthrombi was significantly increased in both cerebral cortex and cerebellar cortex at 7 days after SAH (p <0.01). Simvastatin treatment down-regulated the formation of microclots in this SAH model and the number of microthombi was decreased significantly in the SAH+simvastatin group compared to the SAH or SAH+vehicle groups (p <0.01). In conclusion, simvastatin administration attenuates cerebral vasospasm and alleviates microthrombosis in the late phase of SAH in this prechiasmatic blood injection model.
尽管先前的研究表明辛伐他汀可减轻蛛网膜下腔出血（SAH）后的脑血管痉挛，但其对SAH后继发性病理生理变化的影响尚未得到研究。越来越多的证据表明，SAH诱导的微血栓形成在迟发性脑缺血的发病机制中起重要作用。然而，迄今为止，尚无研究关注SAH模型中微血栓的治疗。本研究的目的是确定辛伐他汀对大鼠SAH后微血栓形成的影响。成年雄性SD大鼠分为四组：（1）对照组（n = 6）；（2）SAH组（n = 6）；（3）SAH+溶剂组（n = 6）和（4）SAH+辛伐他汀组（n = 6）。通过用注射泵在20秒内将0.3 ml新鲜动脉非肝素化血液注入视交叉前池来诱导SAH。在SAH+辛伐他汀组中，SAH后以20 mg/kg/d的剂量腹腔注射辛伐他汀。SAH后7天进行灌注固定，然后切除脑样本。测量大脑中动脉和大脑前动脉的横截面积。通过苏木精-伊红（H&E）染色评估微凝块。通过纤维蛋白（原）免疫染色测量微血栓形成。结果表明，给予辛伐他汀可预防SAH后第7天的血管痉挛（p<0.01）。SAH后7天，大脑皮质和小脑皮质中的微血栓数量均显著增加（p<0.01）。在该SAH模型中，辛伐他汀治疗下调了微凝块的形成，与SAH组或SAH+溶剂组相比，SAH+辛伐他汀组中的微血栓数量显著减少（p<0.01）。总之，在该视交叉前池血液注射模型中，给予辛伐他汀可减轻SAH后期的脑血管痉挛并缓解微血栓形成。
