Li Shengjie, Tian Ye, Huang Xintao, Zhang Yongqiang, Wang Dehui, Wei Huijie, Dong Jingfei, Jiang Rongcai, Zhang Jianning
Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Neurological Institute, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China.
Puget Sound Blood Research Institute, 1551 Eastlake Ave E, Seattle, WA 98102, USA.
Brain Res. 2014 Dec 17;1593:65-75. doi: 10.1016/j.brainres.2014.09.077. Epub 2014 Oct 12.
Cerebral aneurysm (CA) rupture is a major cause of subarachnoid hemorrhage with high morbidity and mortality. Using an animal model, we examined the potential of endothelial colony-forming cells (ECFCs) transfusion on vascular degeneration after CA induction and underlying mechanisms. CA was induced in the right anterior cerebral artery-olfactory artery (ACA/OA) bifurcations in Sprague-Dawley rats with or without ECFCs transfusion. The degeneration of internal elastic lamina (IEL), media thickness and CA size were evaluated. Expression of matrix metalloproteinase-2 and 9 (MMP-2 and 9), tissue inhibitor of metalloproteinase-1 (TIMP-1), macrophage chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), nuclear factor κB (NF-κB), endothelial nitric oxide synthase (eNOS), B-cell leukemia/lymphoma-2 (Bcl-2), and inducible nitric oxide synthase (iNOS) were analyzed by quantitative real-time polymerase chain reaction. The macrophages infiltration and apoptosis of smooth muscle cells (SMCs) were examined immunohistologically. Rats in CA+ECFCs transfusion group showed a notable reduction in IEL degeneration, media thinning and CA size compared with those in CA+saline group. ECFCs transfusion inhibited the MMP-driven wall destruction by downregulating MMP-2, MMP-9 expression and upregulating TIMP-1. ECFCs transfusion dramatically decreased VCAM-1 and NF-κB expression, increased eNOS expression and caused no change in MCP-1 expression, which was accompanied by reduced macrophages infiltration. Moreover, ECFCs transfusion reversed downregulation of Bcl-2 expression and upregulation of iNOS expression, and decreased SMCs apoptosis. Collectively, these findings suggest that ECFCs transfusion confers protection against degeneration of aneurysmal wall by inhibiting inflammatory cascades and SMCs apoptosis.
脑动脉瘤（CA）破裂是蛛网膜下腔出血的主要原因，具有较高的发病率和死亡率。我们使用动物模型，研究了内皮祖细胞（ECFCs）输注对CA诱导后血管退变的潜在作用及其潜在机制。在有或没有ECFCs输注的情况下，在Sprague-Dawley大鼠的右大脑前动脉-嗅动脉（ACA/OA）分叉处诱导CA。评估内弹性膜（IEL）的退变、中膜厚度和CA大小。通过定量实时聚合酶链反应分析基质金属蛋白酶-2和9（MMP-2和9）、金属蛋白酶组织抑制剂-1（TIMP-1）、巨噬细胞趋化蛋白-1（MCP-1）、血管细胞黏附分子-1（VCAM-1）、核因子κB（NF-κB）、内皮型一氧化氮合酶（eNOS）、B细胞淋巴瘤-2（Bcl-2）和诱导型一氧化氮合酶（iNOS）的表达。通过免疫组织学检查巨噬细胞浸润和平滑肌细胞（SMCs）的凋亡。与CA+生理盐水组相比，CA+ECFCs输注组大鼠的IEL退变、中膜变薄和CA大小显著降低。ECFCs输注通过下调MMP-2、MMP-9表达和上调TIMP-1来抑制MMP驱动的管壁破坏。ECFCs输注显著降低VCAM-1和NF-κB表达，增加eNOS表达，且MCP-1表达无变化，同时巨噬细胞浸润减少。此外，ECFCs输注逆转了Bcl-2表达的下调和iNOS表达的上调，并减少了SMCs凋亡。总的来说，这些发现表明ECFCs输注通过抑制炎症级联反应和SMCs凋亡，对动脉瘤壁退变具有保护作用。
