Effect of Propofol Post-treatment on Blood-Brain Barrier Integrity and Cerebral Edema After Transient Cerebral Ischemia in Rats
Effect of Propofol Post-treatment on Blood-Brain Barrier Integrity and Cerebral Edema After Transient Cerebral Ischemia in Rats
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DOI：
10.1007/s11064-013-1136-7
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发表时间：
2013-11-01
影响因子：
4.4
通讯作者：
Koo, Bon-Nyeo
中科院分区：
文献类型：
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作者：
Lee, Jae Hoon;Cui, Hui Song;Koo, Bon-Nyeo
虽然异丙酚已被报道对脑缺血损伤提供神经保护，但其对脑缺血后脑水肿的影响尚不清楚。本研究旨在探讨异丙酚后处理对短暂性脑缺血后血脑屏障（BBB）完整性和脑水肿的影响及其作用机制，重点关注水通道蛋白（AQPs）、基质金属蛋白酶（MMPs）和缺氧诱导因子(HIF)-1 α的调节作用。雄性Sprague-Dawley大鼠（n = 78）闭塞右大脑中动脉1小时，致脑缺血。异丙酚后处理，从再灌注开始1小时，给予异丙酚1 mg kg(-1) min（-1）。19只接受假手术的大鼠也被纳入调查。再灌注24 h后，分别通过量化脑含水量和Evans蓝外渗来评估水肿和血脑屏障完整性。再灌注后24 h检测AQP-1、AQP-4、MMP-2、MMP-9的表达，再灌注后8 h检测HIF-1 α的表达。与盐水对照组相比，异丙酚治疗后显著减少脑水肿（P < 0.05）和血脑屏障破坏（P < 0.05）。异丙酚后处理组缺血/再灌注后24 h AQP-1、AQP-4、MMP-2、MMP-9及8 h HIF-1 α的表达均显著降低（P < 0.05）。异丙酚治疗后减轻短暂性脑缺血后脑水肿，与AQP-1、AQP-4、MMP-2和MMP-9的表达降低有关。异丙酚后处理后AQPs和MMPs表达降低可能与抑制HIF-1 α表达有关。
Although propofol has been reported to offer neuroprotection against cerebral ischemia injury, its impact on cerebral edema following ischemia is not clear. The objective of this investigation is to evaluate the effects of propofol post-treatment on blood-brain barrier (BBB) integrity and cerebral edema after transient cerebral ischemia and its mechanism of action, focusing on modulation of aquaporins (AQPs), matrix metalloproteinases (MMPs), and hypoxia inducible factor (HIF)-1 alpha. Cerebral ischemia was induced in male Sprague-Dawley rats (n = 78) by occlusion of the right middle cerebral artery for 1 h. For post-treatment with propofol, 1 mg kg(-1) min(-1) of propofol was administered for 1 h from the start of reperfusion. Nineteen rats undergoing sham surgery were also included in the investigation. Edema and BBB integrity were assessed by quantification of cerebral water content and extravasation of Evans blue, respectively, following 24 h of reperfusion. In addition, the expression of AQP-1, AQP-4, MMP-2, and MMP-9 was determined 24 h after reperfusion and the expression of HIF-1 alpha was determined 8 h after reperfusion. Propofol post-treatment significantly reduced cerebral edema (P < 0.05) and BBB disruption (P < 0.05) compared with the saline-treated control. The expression of AQP-1, AQP-4, MMP-2, and MMP-9 at 24 h and of HIF-1 alpha at 8 h following ischemia/reperfusion was significantly suppressed in the propofol post-treatment group (P < 0.05). Propofol post-treatment attenuated cerebral edema after transient cerebral ischemia, in association with reduced expression of AQP-1, AQP-4, MMP-2, and MMP-9. The decreased expression of AQPs and MMPs after propofol post-treatment might result from suppression of HIF-1 alpha expression.