黃體激素經Akt傳遞使得endothelial nitric oxide synthase表現增加而緩解蜘蛛膜下腔出血所引起之血管痙攣

Progesterone attenuates experimental subarachnoid hemorrhage-induced vasospasm by upregulation of endothelial nitric oxide synthase via Akt signaling pathway

張家茂(Chia-Mao Chang)

指導教授 ： 林志隆

高雄醫學大學/醫學院/醫學研究所/基礎醫學組/碩士(2014年)

https://doi.org/10.6832/KMU.2014.00031

摘要

腦血管痙攣是造成動脈瘤性蛛網膜下腔出血（SAH）患者主要死亡和致病病因。然而，血管痙攣的機制和適當治療仍然還不清楚。在本研究中，我們使用兩次出血囓齒動物模型造成蛛網膜下腔出血，藉此評估黃體激素在蛛網膜下腔出血致腦血管痙攣中可能的效果和機制。我們在SAH誘導後一小時，在去卵巢雌性SD大鼠皮下注射黃體激素（ 8毫克/公斤）。血管痙攣的程度是由第一次蛛網膜下腔出血後7天，平均基底動脈的橫截面面積來確定。我們測量內皮型一氧化氮合成酶（eNOS ）和磷酸化Akt在基底動脈的表現量。在大鼠灌注固定前，記錄的控制和生理參數治療組間無顯著差異。黃體激素治療組別顯著的減緩SAH引起的血管痙攣（ P <0.01）。黃體激素的治療也可緩解蛛網膜下腔出血引起的eNOS蛋白和磷酸化Akt的抑制。這一結果進一步證實，黃體激素是能有效預防SAH引發的血管痙攣。黃體激素的治療效果，在某種程度上，與經由SAH後的Akt信號路徑而使得eNOS表達的增加。所以黃體激素對腦SAH引發之血管痙攣具有療效，這值得更進一步的研究來證實。

關鍵字

黃體激素 ； 蜘蛛膜下腔出血 ； 一氧化氮合成酶

並列摘要

Cerebral vasospasm is the leading cause of mortality and morbidity in patients after aneurysmal subarachnoid hemorrhage (SAH). However, the mechanism and adequate treatment of vasospasm are still illusive. In the present study, we evaluate the effect and possible mechanism of progesterone on SAH-induced vasospasm in a two-hemorrhage rodent model of SAH. Progesterone (8 mg/kg) was subcutaneously injected in ovariectomized female Sprague-Dawley rats one hour after SAH induction. The degree of vasospasm was determined by averaging the cross sectional areas of basilar artery 7 days after first SAH. Expressions of endothelial nitric oxide synthase (eNOS) and phosphorylated Akt (phospho-Akt) in basilar arteries were evaluated. Prior to perfusion-fixation, there were no significant differences among the control and treated groups in physiological parameters recorded. Progesterone-treatment significantly (p<0.01) attenuated SAH-induced vasospasm. The SAH-induced suppression of eNOS protein and phospho-Akt were relieved by progesterone treatment. This result further confirmed that progesterone is effective in preventing SAH-induced vasospasm. The beneficial effect of progesterone may be in part related to upregulation of expression of eNOS via Akt signaling pathway after SAH. Progesterone holds therapeutic promise in the treatment of cerebral vasospasm following SAH.

並列關鍵字

progesterone ； subarachnoid hemorrhage ； nitric oxide syntahse

參考文獻

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