Chang Chia-Mao, Su Yu-Feng, Chang Chih-Zen, Chung Chia-Li, Tsai Yee-Jean, Loh Joon-Khim, Lin Chih-Lung
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan ; Department of Neurosurgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan ; Department of Surgery, Kaohsiung Municipal Hsiao Kang Hospital, No. 482, Shanming Road, Siaogang District, Kaohsiung 81267, Taiwan.
Department of Neurosurgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan ; Faculty of Medicine, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan.
Biomed Res Int. 2014;2014:207616. doi: 10.1155/2014/207616. Epub 2014 May 13.
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 elusive. 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 might 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.
脑血管痉挛是动脉瘤性蛛网膜下腔出血（SAH）患者死亡和发病的主要原因。然而，血管痉挛的机制和适当治疗方法仍不明确。在本研究中，我们在双次出血的SAH啮齿动物模型中评估孕酮对SAH诱导的血管痉挛的作用及可能机制。在SAH诱导后1小时，对去卵巢的雌性Sprague-Dawley大鼠皮下注射孕酮（8mg/kg）。通过计算首次SAH后7天基底动脉的横截面积平均值来确定血管痉挛程度。评估基底动脉中内皮型一氧化氮合酶（eNOS）和磷酸化Akt（p-Akt）的表达。在灌注固定前，对照组和治疗组记录的生理参数无显著差异。孕酮治疗显著（P<0.01）减轻了SAH诱导的血管痉挛。孕酮治疗缓解了SAH诱导的eNOS蛋白和p-Akt的抑制。该结果进一步证实孕酮对预防SAH诱导的血管痉挛有效。孕酮的有益作用可能部分与SAH后通过Akt信号通路上调eNOS表达有关。孕酮在治疗SAH后的脑血管痉挛方面具有治疗前景。
