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缓激肽受体在实验性蛛网膜下腔出血后继发性脑损伤发展中的作用。

Contribution of bradykinin receptors to the development of secondary brain damage after experimental subarachnoid hemorrhage.

机构信息

Department of Neurosurgery, University of Munich Medical Center-Grosshadern, Ludwig-Maximilians University, Munich, Germany.

出版信息

Neurosurgery. 2011 Apr;68(4):1118-23. doi: 10.1227/NEU.0b013e31820a0024.

DOI:10.1227/NEU.0b013e31820a0024
PMID:21242838
Abstract

BACKGROUND

Subarachnoid hemorrhage (SAH) is the stroke subtype with the highest mortality and morbidity. Which molecular events mediate brain damage after SAH is not well understood.

OBJECTIVE

To investigate the role of proinflammatory bradykinin B(1) and B(2) receptors for the pathophysiology of SAH.

METHODS

B(1) and B(2) receptor knockout or wild-type mice were subjected to SAH by endovascular puncture. Intracranial pressure, regional cerebral blood flow, and mean arterial blood pressure were continuously monitored up to 60 minutes after SAH. Brain water content was quantified 24 hours after SAH; mortality, neurological function, and body weight were assessed daily for 7 days after hemorrhage.

RESULTS

Intracranial pressure, regional cerebral blood flow, and mean arterial blood pressure did not differ between groups. Mortality was 60% in wild-type mice and 82% in B(1)R mice but only 20% in B(2)R animals (P < .05). B(2)R mice also exhibited less severe neurological deficits (P < .05), a less pronounced loss of body weight (P < .05), and significantly less brain edema formation (P < .05) compared with wild-type mice.

CONCLUSION

Signaling mediated by bradykinin B(2) receptors contributes to mortality and secondary brain damage after SAH in mice. Thus, B(2) receptors may represent novel targets for the treatment of SAH.

摘要

背景

蛛网膜下腔出血(SAH)是死亡率和发病率最高的中风类型。哪些分子事件介导了 SAH 后的脑损伤还不是很清楚。

目的

研究促炎缓激肽 B(1)和 B(2)受体在 SAH 病理生理学中的作用。

方法

通过血管内穿刺使 B(1)和 B(2)受体敲除或野生型小鼠发生 SAH。在 SAH 后长达 60 分钟内连续监测颅内压、局部脑血流和平均动脉血压。SAH 后 24 小时定量脑水含量;出血后 7 天每天评估死亡率、神经功能和体重。

结果

各组之间颅内压、局部脑血流和平均动脉血压没有差异。野生型小鼠的死亡率为 60%,B(1)R 小鼠为 82%,而 B(2)R 动物仅为 20%(P <.05)。与野生型小鼠相比,B(2)R 小鼠还表现出较轻的神经功能缺损(P <.05)、体重减轻程度较轻(P <.05)和脑水肿形成明显减少(P <.05)。

结论

缓激肽 B(2)受体介导的信号转导导致了小鼠 SAH 后的死亡率和继发性脑损伤。因此,B(2)受体可能是治疗 SAH 的新靶点。

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