Role of XIAP gene overexpressed bone marrow mesenchymal stem cells in the treatment of cerebral injury in rats with cerebral palsy
Role of XIAP gene overexpressed bone marrow mesenchymal stem cells in the treatment of cerebral injury in rats with cerebral palsy
复制标题
XIAP基因过表达骨髓间充质干细胞治疗脑瘫大鼠脑损伤的作用
DOI：
10.1186/s12935-019-0988-6
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发表时间：
2019-10-23
影响因子：
5.8
通讯作者：
Teng, Junfang
中科院分区：
文献类型：
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作者：
Deng, Wenjing;Fan, Chenghe;Teng, Junfang
本研究旨在探讨腺病毒介导的X-linked inhibitor of apoptosis protein （XIAP）过表达骨髓间充质干细胞（BMSCs）对脑瘫（CP）大鼠脑损伤的影响。方法培养鉴定大鼠骨髓间充质干细胞。用腺病毒表达载体Ad-XIAP-GFP修饰BMSCs的XIAP基因。结扎左颈总动脉，缺氧2 h，建立CP缺血缺氧大鼠模型，脑室内注射骨髓间充质干细胞。采用RT-qPCR和western blot检测各组大鼠脑组织中XIAP mRNA和蛋白的表达。通过一系列试验，观察CP大鼠的神经行为、乙酰胆碱（Ach）含量、乙酰胆碱酯酶（AchE）活性、脑病理损伤、脑神经细胞凋亡及星形胶质细胞活化情况。结果CP大鼠表现出明显的异常，乙酰胆碱酯含量升高，乙酰胆碱酯酶活性降低，病理损伤明显，脑神经细胞凋亡增加，星形胶质细胞活化升高。XIAP过表达BMSCs可改善CP大鼠的神经行为状况，降低Ach含量，提高AchE活性，减轻脑病理损伤，抑制脑神经细胞凋亡和星形胶质细胞活化。结论我们的研究表明，XIAP过表达的骨髓间充质干细胞可以抑制脑神经细胞的凋亡和星形胶质细胞的活化，增加AchE活性，抑制Ach含量，从而降低大鼠脑缺血缺氧引起的CP。
Background This study is performed to investigate the effects of adenovirus-mediated X-linked inhibitor of apoptosis protein (XIAP) overexpressed bone marrow mesenchymal stem cells (BMSCs) on brain injury in rats with cerebral palsy (CP). Methods Rat's BMSCs were cultured and identified. The XIAP gene of BMSCs was modified by adenovirus expression vector Ad-XIAP-GFP. The rat model of CP with ischemia and anoxia was established by ligating the left common carotid artery and anoxia for 2 h, and BMSCs were intracerebroventricularly injected to the modeled rats. The mRNA and protein expression of XIAP in brain tissue of rats in each group was detected by RT-qPCR and western blot analysis. The neurobehavioral situation, content of acetylcholine (Ach), activity of acetylcholinesterase (AchE), brain pathological injury, apoptosis of brain nerve cells and the activation of astrocytes in CP rats were determined via a series of assays. Results Rats with CP exhibited obvious abnormalities, increased Ach content, decreased AchE activity, obvious pathological damage, increased brain nerve cell apoptosis, as well as elevated activation of astrocyte. XIAP overexpressed BMSCs improved the neurobehavioral situation, decreased Ach content and increased AchE activity, attenuated brain pathological injury, inhibited apoptosis of brain nerve cells and the activation of astrocytes in CP rats. Conclusion Our study demonstrates that XIAP overexpressed BMSCs can inhibit the apoptosis of brain nerve cells and the activation of astrocytes, increase AchE activity, and inhibit Ach content, so as to lower the CP caused by cerebral ischemia and hypoxia in rats.