Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China.
Acta Neurochir (Wien). 2010 May;152(5):861-7. doi: 10.1007/s00701-010-0602-0. Epub 2010 Mar 2.
Adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, are important inflammatory mediators which are elevated in the serum of patients following aneurysmal subarachnoid hemorrhage (SAH). The authors previously found that 6-mercaptopurine (6-mp) was effective in preventing and reversing arterial narrowing in a rodent SAH model. The present study was to examine whether levels of adhesion molecules were altered after treatment with 6-mp in this animal model.
Animals were each injected with autologous blood into the cisterna magna, and intraperitoneal treatment with 6-mp (2 mg/kg) was initiated 1 h before (prevention) or later (treatment). The compound was subsequently administered at 24 and 48 h post-SAH. Blood samples were collected at 72 h post-SAH to measure ICAM-1, VCAM-1, and E-selectin levels. The basilar arteries were harvested and sliced, and their cross-sectional areas were measured. Morphologically, convolution of the internal elastic lamina, distorted endothelial wall, and myonecrosis of the smooth muscle were prominently observed in the SAH only and vehicle-treated SAH groups, but not in the 6-mp-treated SAH group or in healthy controls. No significant differences were found in the levels of VCAM-1 among all groups. However, the levels of E-selectin were increased in all animals subjected to SAH (SAH only and SAH plus vehicle groups) compared with healthy controls (no SAH), but not in the 6-mp group (SAH plus 6-mp treatment and preventive treatment with 6-mp).Likewise, the levels of ICAM-1 in the SAH only and SAH plus vehicle groups were significantly elevated (p < 0.001), and pretreatment and treatment with 6-mp reduced ICAM-1 to control levels.
These results show that ICAM-1 and E-selectin may play a role in mediating SAH-induced vasospasm and that a reduction of both adhesive molecules after SAH may partly contribute to the antispastic effect of 6-mp.
细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）和 E-选择素等黏附分子是重要的炎症介质，在蛛网膜下腔出血（SAH）患者的血清中升高。作者先前发现，6-巯基嘌呤（6-MP）在啮齿动物 SAH 模型中可有效预防和逆转动脉狭窄。本研究旨在探讨该动物模型中，6-MP 治疗后黏附分子水平是否发生变化。
动物均被注入自体血到枕大池，在 1 小时前（预防）或之后（治疗）给予腹腔内 6-MP（2mg/kg）治疗。该化合物随后在 SAH 后 24 和 48 小时给予。在 SAH 后 72 小时采集血液样本以测量 ICAM-1、VCAM-1 和 E-选择素水平。采集基底动脉并切片，测量其横截面积。形态学上，仅在 SAH 组和给予载体的 SAH 组中明显观察到内弹性膜的卷曲、内皮壁的扭曲和平滑肌的坏死，而在给予 6-MP 的 SAH 组或健康对照组中则没有。所有组的 VCAM-1 水平无显著差异。然而，与健康对照组（无 SAH）相比，所有 SAH 动物（仅 SAH 组和 SAH 加载体组）的 E-选择素水平升高，但 6-MP 组（SAH 加 6-MP 治疗和预防治疗）则没有。同样，仅 SAH 组和 SAH 加载体组的 ICAM-1 水平显著升高（p<0.001），6-MP 的预处理和治疗将 ICAM-1 降低至对照水平。
这些结果表明，ICAM-1 和 E-选择素可能在介导 SAH 引起的血管痉挛中起作用，SAH 后两种黏附分子的减少可能部分有助于 6-MP 的抗痉挛作用。
