骨髓间充质干细胞移植联合依达拉奉抑制脑梗死后的神经元凋亡

背景：国内外多项研究证实骨髓间充质干细胞移植对脑梗死组织具有一定的神经保护作用。依达拉奉是一种新型强效小分子羟自由基清除剂，可通过清除脑梗死产生的自由基，抑制神经细胞损伤，从而起到脑保护作用。 目的：观察骨髓间充质干细胞移植联合依达拉奉对大鼠脑梗死组织水通道蛋白4、Bcl-2、脑源性神经营养因子表达的影响。 方法：选取Wistar大鼠80只，建立右侧大脑中动脉闭塞模型，随机分为对照组、骨髓间充质干细胞组、依达拉奉组和联合治疗组。建模6h后通过尾静脉分别注入移植液，对照组注射培养液，骨髓间充质干细胞组注射骨髓间充质干细胞，依达拉奉组给予依达拉奉注射液，联合组同时注入骨髓间充质干细胞和依达拉奉注射液。分别在伤后72 h将大鼠麻醉后断头取脑，应用RT-PCR、Western Blot法检测脑组织中水通道蛋白4、Bcl-2、脑源性神经营养因子基因表达和蛋白合成变化。伤后12，24，36 h取大鼠脑组织以TUNEL法测定细胞凋亡情况。 结果与结论：RT-PCR、Western Blot结果显示，在骨髓间充质干细胞与依达拉奉联合治疗组中，Bcl-2、脑源性神经营养因子的表达明显高于骨髓间充质干细胞组、依达拉奉组及对照组（P〈0.05）；而水通道蛋白4的表达低于其余各组（P 〈0.05）。TUNEL测定结果显示，联合治疗组中免疫组化呈棕色的凋亡细胞明显少于单独治疗组及对照组。提示骨髓间充质干细胞移植与依达拉奉联合应用治疗大鼠脑梗死，可进一步促进损伤局部脑源性神经营养因子及 Bcl-2的表达，对神经细胞凋亡具有明显的抑制作用，同时可下调水通道蛋白4水平，减轻脑水肿程度，二者联合运用的效果明显优于单独治疗组。

Bone marrow mesenchymal stem cell transplantation combined with edaravone inhibits neuronal apoptosis after cerebral infarction

BACKGROUND：Several studies have confirmed that bone marrow mesenchymal stem celltransplantation exerts a certain neuroprotective role in cerebral infarction. Edaravone is a novel potent smal-molecule hydroxyl radical scavenger, which play a protective role in the brain by eliminating free radicals and inhibiting nerve celldamage after cerebral infarction. OBJECTIVE：To explore the influence of bone marrow mesenchymal stem cells combined with edaravone on expressions of aquaporin-4, Bcl-2, and brain-derived neurotrophic factor after cerebral infarction in rats. METHODS：Eighty Wistar rats were selected to establish models of cerebral infarction by right middle cerebral artery occlusion, and then randomly divided into control group, bone marrow mesenchymal stem cells group, edaravone group and edaravone＋bone marrow mesenchymal stem cells group （combination group）. After 6 hours of modeling, rats from these four groups were respectively injected via the tail vein with PBS, bone marrow mesenchymal stem cells, edaravone and edaravone＋bone marrow mesenchymal stem cells. After 72 hours, the＆amp;nbsp;rats were decapitated to take brain tissues. Consequently, expressions of aquaporin-4, Bcl-2, and brain-derived neurotrophic factor mRNA and protein were determined by RT-PCR and western blot methods. After 12, 24 and 36 hours, TUNEL method was used for the determination of cellapoptosis. RESULTS AND CONCLUSION：The expressions of Bcl-2 and brain-derived neurotrophic factor were higher in the combination group than the other three groups （P〈0.05）, but the expression of aquaporin-4 was lowest in the combination group （P〈0.05）. The number of apoptotic cells in the combination group was significantly lower than that in the other three groups. These findings suggest that the combination of bone marrow mesenchymal stem cells and edaravone can improve expressions of Bcl-2 and brain-derived neurotrophic factor in the injured site, and significantly inhibit neuronal apoptosis. Meanwhile, the combination therapy can decrease expression of aquaporin-4 and mitigate cerebral edema, which is superior to bone marrow mesenchymal stem celltransplantation and edaravone alone.