The protective effects of preconditioning on cerebral endothelial cells in vitro
The protective effects of preconditioning on cerebral endothelial cells in vitro
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DOI：
10.1097/01.wcb.0000091762.61714.fe
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发表时间：
2003-11-01
影响因子：
6.3
通讯作者：
Keep, RF
中科院分区：
文献类型：
--
作者：
Andjelkovic, AV;Stamatovic, SM;Keep, RF
缺血预处理（PC）可以显着减少随之而来的缺血性损伤。尽管大多数注意力都集中在 PC 的神经元效应上，但作者最近表明，缺血性 PC 可以减少缺血引起的脑血管损伤。在体内，很难确定这是否是PC的直接脑血管作用。因此，本研究检验了脑内皮细胞是否可以在没有其他细胞类型的情况下在体外进行预处理。实验在永生化小鼠脑内皮细胞系或小鼠脑微血管内皮细胞的原代培养物上进行。细胞暴露于短时间的氧糖剥夺（OGD）（作为 PC 刺激），或长时间（5 小时），有或没有再氧合，以诱导内皮损伤。通过测量乳酸脱氢酶的释放以及蛋白质和 mRNA 水平的细胞间粘附分子 1 的表达来评估内皮损伤。实验表明，1 小时的 OGD 是最佳的 PC 刺激，而 1 天或 3 天的间隔是 PC 刺激和伤害事件之间的最佳时间间隔。预处理细胞在OGD（+/-复氧）期间乳酸脱氢酶释放较少，并且在OGD复氧后细胞间粘附分子1表达减少。这项研究表明脑内皮细胞可以直接进行预处理。这种现象在 PC 对大脑的总体影响中的重要性仍有待阐明。了解 PC 引起的保护机制可能有助于了解如何预防缺血引起的血管损伤（例如出血性转化）。
Ischemic preconditioning (PC) can markedly reduce ensuing ischemic damage. Although most attention has focused on the neuronal effects of PC, the authors have recently shown that ischemic PC reduces ischemia-induced cerebrovascular damage. In vivo, it is difficult to ascertain whether this is a direct cerebrovascular effect of PC. This study, therefore, examined whether cerebral endothelial cells can be preconditioned in vitro in the absence of other cell types. Experiments were performed on an immortalized mouse brain endothelial cell line or primary cultures of mouse brain microvessel endothelial cells. Cells were exposed to oxygen glucose deprivation (OGD) of either short duration, as a PC stimulus, or a long duration (5 hours) with or without reoxygenation to induce endothelial damage. Endothelial injury was assessed by measuring lactate dehydrogenase release and the expression of intercellular adhesion molecule-1 at the protein and mRNA levels. Experiments indicated that I hour of OGD was the optimal PC stimuli and that a I or 3 day interval was the optimal time interval between the PC stimulus and the injurious event. Preconditioned cells had less lactate dehydrogenase release during OGD (+/- reoxygenation) and reduced intercellular adhesion molecule-1 expression after OGD with reoxygenation. This study shows that cerebral endothelial cells can be directly preconditioned. The importance of this phenomenon in the overall effects of PC on the brain remains to be elucidated. Understanding the protective mechanisms elicited by PC may give insight into how to prevent ischemia-induced vascular damage (e.g., hemorrhagic transformation).