Department of Neurology, Affiliated Huashan Hospital of Fudan University, Shanghai 200036, China; Department of Neurology, Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou 550004, China.
Chin Med J (Engl). 2013;126(18):3433-8.
Endothelin-1 (ET-1) has deleterious effects on water homeostasis, cerebral edema, and blood-brain barrier (BBB) integrity. Highly expressed ET-1 was observed after intracerebral hemorrhage (ICH); however, ET-1 changes and their relationship with BBB disruption within 24 hours of ICH have not been thoroughly investigated. The aim of the present study was to observe the changes in perihematomal ET-1 levels in various phases of ICH and their correlation with the BBB integrity in a rabbit model of ICH.
Twenty-five rabbits (3.2-4.3 kg body weight) were randomly divided into a normal control group (five rabbits) and a model group (20 rabbits). Animals in the model group were equally divided into four subgroups (five rabbits each to be sacrificed at 6, 12, 18, and 24 hours following ICH establishment). An ICH model was prepared in the model group by infusing autologous arterial blood into the rabbit brain. ET-1 expression in perihematomal brain tissues was determined using immunohistochemistry and color image analysis, and the permeability of the BBB was assayed using the Evan's Blue (EB) method. A repeated measures analysis of variance was used to make comparisons of the ET-1 and EB content across the entire time series.
The number of perihematomal endothelial cells with ET-1 positive expressions following 6, 12, 18, and 24 hours ICH model establishment was 9.32, 13.05, 15.90, and 20.44, respectively, but as low as 6.67 in the control group. The average transmittance of ET-1-positive cell bodies at 6, 12, 18, and 24 hours after ICH was 99.10, 97.40, 85.70, and 80.80, respectively, but 100.12 in the control group. These data reveal that the expression of ET-1 was significantly increased at 6, 12, 18, and 24 hours after ICH compared with the control group, and a marked decrease in the average transmittance of ET-1-positive cell bodies was noted (P < 0.05). Similarly, the perihematomal EB content at 6, 12, 18, and 24 hours after ICH was 29.39 ± 1.16, 32.20 ± 0.73, 33.63 ± 1.08, and 35.26 ± 1.12, respectively, in the model group and 28.06 ± 0.80 in the control group. The results indicate that a significant increase in the EB content in the model group was observed compared with that of the control group (P < 0.05). Moreover, a positive correlation between the number of ET-1-positive endothelial cells and BBB permeability was observed (r = 0.883, P < 0.05).
High levels of ET-1 are closely associated with BBB disruption. ET-1 may play an important role in the pathogenesis of secondary brain injury after ICH.
内皮素-1（ET-1）对水稳态、脑水肿和血脑屏障（BBB）完整性具有有害影响。在脑出血（ICH）后观察到 ET-1 高度表达；然而，ICH 后 24 小时内 ET-1 变化及其与 BBB 破坏的关系尚未得到彻底研究。本研究的目的是观察兔 ICH 模型中不同阶段血肿周围 ET-1 水平的变化及其与 BBB 完整性的相关性。
25 只（体重 3.2-4.3kg）兔子被随机分为正常对照组（5 只兔子）和模型组（20 只兔子）。模型组动物等分为 4 个亚组（每组 5 只，分别在 ICH 后 6、12、18 和 24 小时处死）。通过向兔脑内注入自体动脉血制备 ICH 模型。采用免疫组织化学和彩色图像分析检测血肿周围脑组织中 ET-1 的表达，采用伊文思蓝（EB）法检测 BBB 的通透性。采用重复测量方差分析比较整个时间序列的 ET-1 和 EB 含量。
ICH 模型建立后 6、12、18 和 24 小时，ET-1 阳性表达的血肿周围内皮细胞数分别为 9.32、13.05、15.90 和 20.44，而对照组仅为 6.67。ICH 后 6、12、18 和 24 小时 ET-1 阳性细胞体的平均透射率分别为 99.10、97.40、85.70 和 80.80，而对照组为 100.12。这些数据表明，ICH 后 6、12、18 和 24 小时 ET-1 的表达明显高于对照组，ET-1 阳性细胞体的平均透射率明显降低（P<0.05）。同样，ICH 后 6、12、18 和 24 小时模型组血肿周围 EB 含量分别为 29.39±1.16、32.20±0.73、33.63±1.08 和 35.26±1.12，对照组为 28.06±0.80。结果表明，模型组 EB 含量明显高于对照组（P<0.05）。此外，还观察到 ET-1 阳性内皮细胞数量与 BBB 通透性呈正相关（r=0.883，P<0.05）。
高水平的 ET-1 与 BBB 破坏密切相关。ET-1 可能在 ICH 后继发性脑损伤的发病机制中起重要作用。
