Autologous Bone Marrow Mononuclear Cell Transplantation Delays Progression of Carotid Atherosclerosis in Rabbits.
Autologous Bone Marrow Mononuclear Cell Transplantation Delays Progression of Carotid Atherosclerosis in Rabbits.
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DOI：
10.1007/s12035-015-9347-3
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发表时间：
2016-09
影响因子：
5.1
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Cui K;Ma X;Yu L;Jiang C;Fu C;Fu X;Yu X;Huang Y;Hou S;Si C;Chen Z;Yu J;Wan J;Wang J
骨髓单个核细胞（BMMNCs）可以对抗局灶性缺血性卒中模型中的氧化应激和抑制炎症反应。然而，BMMNC移植对颈动脉粥样硬化的影响需要确定。新西兰白色兔采用球囊损伤加高脂饮食8周的方法建立颈动脉粥样硬化斑块模型。将家兔随机接受静脉注射自体BrdU标记的BMMNC或等体积的磷酸盐缓冲盐水。评价斑块的促炎和抗炎细胞因子、抗氧化蛋白和细胞死亡标志物的表达。移植后第1天BMMNCs向动脉粥样硬化斑块内迁移。在第28天，BMMNC治疗的兔比赋形剂治疗的对照组具有更小的斑块和更多的胶原沉积（p<0.05）。BMMNC治疗显着增加内皮型一氧化氮合酶和抗氧化酶谷胱甘肽过氧化物酶和超氧化物歧化酶相比，第7天的车辆治疗斑块。BMMNC处理的兔也具有较低水平的裂解型半胱天冬酶-3表达;较低水平的促炎细胞因子白细胞介素-1 β、肿瘤坏死因子-α和基质金属蛋白酶9;以及较高水平的胰岛素样生长因子-1及其受体（p<0.05）。自体骨髓基质干细胞移植可抑制动脉粥样硬化斑块的形成，并与增强抗氧化作用、降低炎性细胞因子和切割的caspase-3水平以及增加胰岛素样生长因子-1及其受体的表达有关。BMMNC移植是治疗颈动脉粥样硬化的一种新方法。
Bone marrow mononuclear cells (BMMNCs) can counteract oxidative stress and inhibit the inflammatory response in focal ischemic stroke models. However, the effect of BMMNC transplantation on carotid atherosclerosis needs to be determined. The carotid atherosclerotic plaque model was established in New Zealand White rabbits by balloon injury and 8 weeks of high-fat diet. Rabbits were randomized to receive an intravenous injection of autologous BrdU-labeled BMMNCs or an equal volume of phosphate-buffered saline. Plaques were evaluated for expression of proinflammatory and anti-inflammatory cytokines, antioxidant proteins, and markers of cell death. BMMNCs migrated into atherosclerotic plaque on the first day after cell transplantation. BMMNC-treated rabbits had smaller plaques and more collagen deposition than did the vehicle-treated controls on day 28 (p<0.05). BMMNC treatment significantly increased endothelial nitric oxide synthase and the antioxidant enzymes glutathione peroxidase and superoxide dismutase in plaques compared to vehicle treatment on day 7. BMMNC-treated rabbits also had lower levels of cleaved caspase-3 expression; lower levels of proinflammatory cytokines interleukin-1β, tumor necrosis factor-α, and matrix metalloproteinase 9; and higher levels of insulin-like growth factor-1 and its receptor (p<0.05). Autologous BMMNC transplantation can suppress the process of atherosclerotic plaque formation and is associated with enhanced antioxidative effect, reduced levels of inflammatory cytokines and cleaved caspase-3, and increased expression of insulin-like growth factor-1 and its receptor. BMMNC transplantation represents a novel approach for the treatment of carotid atherosclerosis.