Zheng Yue-Ying, Lan Yun-Ping, Tang Hui-Fang, Zhu Sheng-Mei
Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, 310003, HangZhou, People's Republic of China.
Anesth Analg. 2008 Dec;107(6):2009-16. doi: 10.1213/ane.0b013e318187c313.
Cerebral edema is a major threat for stroke victims. Most studies have focused on the neuroprotective activities of propofol, addressing infarct volume rather than cerebral edema. Aquaporin-4 (AQP4) plays an important role in maintaining brain water homeostasis under various neurological insults. We explored the effect of propofol pretreatment on cerebral edema in a rat model of brain ischemia reperfusion and assessed the involvement of AQP4.
To induce brain ischemia reperfusion, we introduced a silicone-coated monofilament nylon suture into the origin of the middle cerebral artery, withdrawing it after 90 min. Treatment groups (n = 32), received propofol (0.1 mL x kg(-1) x min(-1)) infusion for 30 min before occlusion; the vehicle group (n = 32) and the sham-operated group (n = 28), which received the intralipid vehicle at the same time and rate. To assess cerebral infarct volume, we used 2, 3, 5-triphenyl-tetrazolium chloride staining; wet-dry weight ratio was the basis for cerebral edema estimation, and we used immunohistochemistry and Western blot to detect AQP4 expression.
The wet-dry weight ratio decreased from 86.89% +/- 0.71% in the vehicle group (n = 6) to 72.42% +/- 0.74% in the propofol group (n = 6), corresponding to an average decrease of 16%. In parallel and based on immunohistochemical semi-quantification, the propofol group exhibited remarkable attenuation of AQP4 over-expression in the ischemic border zone compared with the vehicle group: 1.28 +/- 0.03 vs 1.40 +/- 0.05, n = 7, respectively; P < 0.05. Values derived from Western blot quantification were similarly decreased in the propofol group compared to the vehicle group: 20.85% +/- 4.18% vs 31.67% +/- 3.23%, n = 4, respectively; P < 0.05. However, infarct volume and neurologic deficit in postischemic rats in the propofol group were not statistically different from values in the vehicle group.
We conclude that prestroke treatment with propofol reduces postischemic cerebral edema in rats, possibly through inhibiting AQP4 over-expression in the boundary zone of ischemia.
脑水肿是中风患者面临的主要威胁。大多数研究集中在丙泊酚的神经保护作用，关注的是梗死体积而非脑水肿。水通道蛋白4（AQP4）在各种神经损伤情况下维持脑水稳态中起重要作用。我们探讨了丙泊酚预处理对脑缺血再灌注大鼠模型脑水肿的影响，并评估了AQP4的参与情况。
为诱导脑缺血再灌注，我们将一根硅胶涂层单丝尼龙缝线插入大脑中动脉起始处，90分钟后取出。治疗组（n = 32）在闭塞前接受丙泊酚（0.1 mL·kg⁻¹·min⁻¹）输注30分钟；载体组（n = 32）和假手术组（n = 28），以相同的时间和速率接受脂质乳剂载体。为评估脑梗死体积，我们使用2,3,5-三苯基四氮唑氯化物染色；湿重与干重之比是评估脑水肿的基础，我们使用免疫组织化学和蛋白质印迹法检测AQP4表达。
湿重与干重之比从载体组（n = 6）的86.89%±0.71%降至丙泊酚组（n = 6）的72.42%±0.74%，平均下降16%。同时，基于免疫组织化学半定量分析，与载体组相比，丙泊酚组在缺血边界区AQP4过表达明显减弱：分别为1.28±0.03和1.40±0.05，n = 7；P < 0.05。蛋白质印迹法定量得出的值在丙泊酚组中与载体组相比同样降低：分别为20.85%±4.18%和31.6
