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[辛伐他汀对大鼠蛛网膜下腔出血后皮质微血栓形成的影响及其机制]

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

作者信息

Zhu Yun, Chen Gang, Wang Zhong

机构信息

Department of Neurosurgery, First Affiliated Hospital, Soochow University, Suzhou 215006, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2012 Dec 18;92(47):3374-6.

PMID:23328604
Abstract

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: (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 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(-1)×d(-1) 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, SAH, 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).

CONCLUSION

The administration of simvastatin alleviates microthrombosis in late phase of SAH in this prechiasmatic blood injection model.

摘要

目的

越来越多的证据表明,蛛网膜下腔出血(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。本研究的目的是确定辛伐他汀对SAH后微血栓形成和脑血管痉挛的影响,并探讨其机制。

方法

将24只成年雄性SD大鼠分为4组:(1)对照组(n = 6);(2)SAH组(n = 6);(3)SAH + 赋形剂组(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诱导SAH。在SAH + 辛伐他汀组中,SAH后以20 mg×kg(-1)×d(-1)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。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

对照组、SAH组、赋形剂组和辛伐他汀组的微血栓数量分别为1±1、25±5、24±4和5±2。SAH后7天,大脑皮质中的微血栓数量显著增加(P < 0.01)。辛伐他汀治疗下调了SAH模型中微凝块的形成,与SAH组或SAH + 赋形剂组相比,SAH + 辛伐他汀组的微血栓数量显著减少(P < 0.01)。

结论

在这个视交叉前池注血模型中,给予辛伐他汀可减轻SAH后期的微血栓形成。

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