Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Army Medical University, Chongqing 400038, China.
State Key Laboratory Of Silkworm Genome Biology, Southwest University, No. 2 Rd Tiansheng, Beibei District of Chongqing, 400715, China.
Brain Res. 2019 Jul 15;1715:41-46. doi: 10.1016/j.brainres.2019.01.033. Epub 2019 Jan 28.
Arginine-vasopressin (AVP) is believed to be positively correlated with the brain edema formation, but the underlying mechanism is still unclear. In this study, we explored the role of the V2 receptors antagonist tolvaptan on brain edema following intracerebral hemorrhage (ICH) with a rat model. Animals were randomly given tolvaptan or vehicle through oral gavage at 12 h, 36 h, and 60 h after ICH surgery. Brain swelling (%), brain water content(BWC), neurological scores, Evans blue fluorescence and blood-brain barrier (BBB) tight junction proteins were measured to evaluate the effect of tolvaptan in ICH. We found that tolvaptan alleviated the brain swelling (%), decreased the BWC growth, and attenuated the neurological deficits after ICH (p < 0.05, vs vehicle). What's more, tolvaptan increased the expression of ZO-1 and occludin (p < 0.05, vs vehicle), which might be attributed to the down-regulated effects of tolvaptan on MMP-9. These results provided evidence supporting the use of tolvaptan for ICH-induced brain edema. Large animal experiments are required to further explore the efficacy and mechanism of tolvaptan in ICH treatment.
精氨酸加压素（AVP）被认为与脑水肿的形成呈正相关，但潜在的机制尚不清楚。在这项研究中，我们通过大鼠模型探索了 V2 受体拮抗剂托伐普坦对脑出血（ICH）后脑水肿的作用。ICH 手术后 12、36 和 60 小时，动物通过口服灌胃随机给予托伐普坦或载体。测量脑肿胀（%）、脑水含量（BWC）、神经评分、伊文思蓝荧光和血脑屏障（BBB）紧密连接蛋白，以评估托伐普坦在 ICH 中的作用。我们发现托伐普坦减轻了脑肿胀（%），降低了 BWC 的增长，并减轻了 ICH 后的神经功能缺损（p<0.05，与载体相比）。此外，托伐普坦增加了 ZO-1 和 occludin 的表达（p<0.05，与载体相比），这可能归因于托伐普坦对 MMP-9 的下调作用。这些结果为托伐普坦治疗 ICH 诱导的脑水肿提供了证据支持。需要进行大动物实验来进一步探索托伐普坦在 ICH 治疗中的疗效和机制。
