Effects of Noggin-Transfected Neural Stem Cells on Neural Functional Recovery and Underlying Mechanism in Rats with Cerebral Ischemia Reperfusion Injury.
Effects of Noggin-Transfected Neural Stem Cells on Neural Functional Recovery and Underlying Mechanism in Rats with Cerebral Ischemia Reperfusion Injury.
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DOI：
10.1016/j.jstrokecerebrovasdis.2017.02.034
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发表时间：
2017-07
期刊：
影响因子：
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通讯作者：
Jun-de Zhu;Jun-Jie Wang;Guo Ge;Chao-sheng Kang
中科院分区：
文献类型：
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作者：
Jun-de Zhu;Jun-Jie Wang;Guo Ge;Chao-sheng Kang
目的探讨转染noggin基因的神经干细胞（neural stem cells，NSCs）对大鼠局灶性脑缺血再灌注损伤（IRI）的保护作用。将含有Noggin的腺病毒载体转染到大鼠神经干细胞中。将大鼠大脑中动脉闭塞2.0小时，再灌注1.0小时，然后在NSC、Noggin + NSC和假手术组中分别将单独的NSC、Noggin转染的NSC和生理盐水注入侧脑室。分别于移植后1、3、7、28 d处死大鼠，测定大鼠行为能力后，采用比色法测定超氧化物歧化酶（SOD）和丙二醛（MDA）含量。Western blot检测血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）蛋白的表达。TUNEL阳性和BrdU/nestin双阳性细胞在光镜下观察和定量分析进行了形态technique. ResultsNoggin转染的神经干细胞显着减少梗死体积和改善神经功能评分。Noggin转染的神经干细胞也减少了凋亡神经元的百分比，减轻了神经元的形态学损伤。Noggin基因转染的神经干细胞移植后，MDA水平明显降低，SOD活性明显升高，BMP 4、VEGF和bFGF蛋白表达水平明显下调。结论Noggin基因修饰的神经干细胞移植对脑血管病具有较好的神经保护作用。
ObjectiveTo investigate neuroprotection of noggin-transfected neural stem cells (NSCs) against focal cerebral ischemia reperfusion injury (IRI) in rats.MethodsEighty Wistar rats were randomly divided into the sham, IRI, NSCs, and noggin + NSCs groups. Noggin containing adenoviral vectors was transfected into rat NSCs. Rats were subjected to 2.0 hours middle cerebral artery occlusion and reperfusion 1.0 hour, followed by infusion into the lateral ventricles of NSCs alone, noggin-transfected NSCs, and saline at 3 days in the NSCs, noggin + NSCs, and sham groups, respectively. All rats were sacrificed on 1, 3, 7, and 28 days after transplantation; the colorimetric method was used to detect the levels of superoxide dismutase (SOD) and the malondialdehyde (MDA) content after the behavior capability determined. Western blot was performed for detecting the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) proteins. The TUNEL-positive and BrdU/nestin double-positive cells were observed under a light microscope and quantitative analysis was performed by morphometric technique.ResultsNoggin-transfected NSCs significantly decreased the infarct volume and improved the neurological scores. Noggin-transfected NSCs also reduced the percentage of apoptotic neurons and relieved neuronal morphological damage. Noggin-transfected NSC transplantation markedly decreased the MDA levels and increased the SOD activity, and simultaneously downregulated the BMP4 (bone morphogenesis protein), VEGF, and bFGF proteins.ConclusionsThe present study demonstrates that grafting NSCs modified by noggin gene provides better neuroprotection for cerebrovascular disease.