| 刘 蕾,胡 建,董 凤,徐 晔,夏 炎,吴 铮.骨髓基质干细胞移植改善慢性酒精中毒大鼠脑损害的相关机制研究[J].现代生物医学进展英文版,2019,19(11):2041-2045. |
| 骨髓基质干细胞移植改善慢性酒精中毒大鼠脑损害的相关机制研究 |
| Effect and Mechanism of Intravenous Bone Marrow Stromal Cells Transplantation Against Chronic Ethanol-induced Brain Damage in Rats |
| Received:April 10, 2019 Revised:April 30, 2019 |
| DOI：10.13241/j.cnki.pmb.2019.11.008 |
| 中文关键词: 骨髓基质干细胞 慢性酒精中毒 凋亡 神经营养因子 PI3K/Akt通路 |
| 英文关键词: Bone marrow stromal cells Chronic alcoholism Apoptosis Neurotrophic factors PI3K/Akt pathways |
| 基金项目:黑龙江省教育厅科学技术研究项目（面上项目）（12511291） |
| Author Name | Affiliation | E-mail | | LIU Lei | Department of Psychiatry, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, 150001, China | maggie.leilei@163.com | | HU Jian | Department of Psychiatry, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, 150001, China | | | DONG Feng | Department of Psychiatry, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, 150001, China | | | XU Ye | Department of Psychiatry, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, 150001, China | | | XIA Yan | Department of Psychiatry, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, 150001, China | | | WU Zheng | Department of Psychiatry, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, 150001, China | |
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| 中文摘要: |
| 摘要 目的：探讨骨髓基质干细胞（bone marrow stormal cells, BMSCs）静脉移植对慢性酒精中毒大鼠脑保护作用的相关机制。方法：体外分离、培养、扩增SD大鼠BMSCs。成年雄性SD大鼠随机分为慢性酒精中毒组、BMSCs回输组、磷酸缓冲盐溶液（phos- phate buffer saline，PBS）回输组和对照组，每组7只。前三组用酒精灌胃8周建立慢性酒精中毒动物模型，对照组不造模（给予蔗糖灌胃），BMSCs回输组和PBS回输组于造模7周时一次性经尾静脉回输BMSCs或PBS。免疫印迹法检测海马Bcl-2、Bax、NGF、BDNF以及信号转导分子p-Akt的表达；反转录PCR检测海马神经生长因子（nerve growth factor, NGF）和脑源性神经营养因子（brain derived neurotrophic factor, BDNF）。结果：BMSCs回输组海马抗凋亡蛋白Bcl-2表达高于其余三组（P<0.05）；促凋亡蛋白Bax表达低于慢性酒精中毒组（P<0.01），与对照组无统计学差异（P=0.989）。BMSCs回输组鼠海马内NGF和BDNF mRNA和蛋白表达、p-Akt蛋白表达均高于其余三组（P<0.05）。结论：静脉移植BMSCs能够明显改善慢性酒精中毒大鼠海马的细胞凋亡；其可能与自或旁分泌BDNF和NGF营养因子有关，且可能部分是通过激活PI3K/Akt通路实现。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect and mechanism of intravenous bone marrow stromal cells (BMSCs) transplantation against chronic ethanol-induced brain damage in rats. Methods: BMSCs from rats were isolated, cultured and identified in vitro. Male Sprague-Dawley rats (n=28) were randomly divided into four groups: chronic ethanol group, BMSCs group, PBS group and control group, BMSCs or PBS were intravenously injected to the rats of BMSCs or PBS group at the 7th week after ethanol gavage, respectively. The expression of Bcl-2, Bax, and phospho-Akt in hippocampus were evaluated by immunoblot. Nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) protein and mRNA expression in hippocampus were analysed by immunoblot and reverse transcrip- tase-polymerase chain reaction (RT-PCR), respectively. Results: We observed that transplated BMSCs significantly reduced the Bax ex- pression (P<0.01) and increased Bcl-2 expression (P<0.05) in hippocampus of ethanol-fed rats. We also found BMSCs transplantation was able to induce upregulaton of NGF of BDNF in hippocampus of ethanol-fed rats at mRNA and protein levels (P<0.05). In addition, we discovered that the phospho-Akt expression was increased in hippocampus of BMSCs transplated rats than that in other three groups(P<0.01). Conclusion: Intravenous BMSCs transplantation is able to shield rat cell apoptotic impairment from chronic alcoholism by au- tocrine/paracrine of neurotrophic factors, which is involved in PI3K/Akt activation, at least partially. |
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