TERT修饰骨髓间充质干细胞移植促进TBI大鼠自噬及认知功能的作用及机制

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摘要目的研究端粒酶逆转录酶（TERT）基因修饰的骨髓间充质干细胞（BMSCs）促进脑创伤（TBI）大鼠脑组织自噬及认知功能的作用，探讨可能的分子机制。方法分离并鉴定大鼠BMSCs，应用pLXSN-TERT病毒重组子转染BMSCs。应用Marmarou方法制备脑创伤TBI大鼠模型。将64只大鼠随机分为四组，分别为TBI组、BMSCs-TBI组和TERT-BMSCs-TBI组和对照组，每组各16只。应用HE染色光镜观察大鼠脑组织结构及病理改变。Western blot检测BDNF、NGF等神经生长因子的蛋白表达水平；检测自噬相关因子Beclin1和Parkin的蛋白表达水平。应用Morris水迷宫方法检测大鼠学习记忆认知功能的改变。结果在Morris水迷宫检测大鼠定位航行试验中，与对照组比较，TBI组平均逃避潜伏期延长（P<0.05）；与TBI组比较，TERT-BMSCs-TBI组、BMSCs-TBI组平均逃避潜伏期缩短（P<0.05）。在空间探索试验中，TBI组大鼠在原平台象限的停留时间明显较对照组大鼠缩短；而TERTBMSCs-TBI组、BMSCs-TBI组与TBI组比较，在原平台象限的停留时间明显延长（P<0.05）。Western blot检测发现，与TBI组比较，BMSCs-TBI组、TERT-BMSCs-TBI组脑皮层组织中BDNF、NGF、Beclin1、Parkin蛋白表达水平均升高（P<0.05）；与BMSCs-TBI组比较，TERT-BMSCs-TBI组显著升高（P<0.05）。结论TERT修饰的BMSCs较普通BMSCs移植TBI大鼠学习记忆认知功能恢复更显著，其分子机制可能与增强自噬功能有关。

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	杨烽

关键词 ：脑创伤, 端粒酶, 骨髓间充质干细胞, 自噬, 认知功能

Abstract：ObjectiveTo investigate the effects of bone marrow mesenchymal stem cells(BMSCs)under modification of telomerase reverse transcriptase(TERT)gene in improving brain tissue autophagy and cognitive function of rats with traumatic brain injury(TBI),as well as to investigate possible molecular mechanisms.MethodsBMCSs of rats was separated and authenticated,pLXSN-TERT virus recombinants were applied to carry out transfection of BMSCs,Marmarou method was adopted to prepare the models of rats with TBI.64 rats were randomly divided into four groups,namely TBI group,BMSCs-TBI group,TERT-BMSCs-TBI group and the control group,with 16 rats in each group.HE light microscopy was used to observe the brain tissue structure of rats and pathologic change.The protein expression levels of BDNF,NGF and other nerve growth factors were detected with Western blot;as well as the protein expression levels of Beclin1 and Parkin relevanttoautophagyweredetectedcorrespondingly.ThenMorris(MorrisWaterMaze)wasappliedtodetectthechangeonlearning and memorizing cognitive function of rats.ResultsAmong Morris detecting place navigation test of rats,the mean escape latency of TBI group prolongs compared to the control group(P<0.05).Compared to TBI group,the TERT-BMSCs-TBI group and BMSCs-TBI group take less mean escape latency(P<0.05).In the space probe trial,the duration of stay of TBI group in original platform quadrant was obviously less than the control group;the duration of stay of TERT-BMSCs-TBI group and BMSCs-TBI group significantly prolong compared to TBI group(P<0.05).Through Western blot detection,the result indicated that expression of protein of BDNF,NGF,Beclin1,Parkin in brain mantle tissue increased obviously in TERT-BMSCs-TBI group and BMSCs-TBI group compared to TBI group(P<0.05),and significantly increased in group TERT-BMSCs-TBI compared with BMSCs-TBI group(P<0.05).ConclusionCompared to general BMSCs transplant,the rats with BMSCs under modification of TERT have more significant learning and memorizing cognitive recovery function,that the molecular mechanism may be related to autophagy function enhancement.

Key words： Traumatic brain injury Telomerase Bone marrow mesenchymal stem cells Autophagy Cognitive function

引用本文:

杨烽. TERT修饰骨髓间充质干细胞移植促进TBI大鼠自噬及认知功能的作用及机制[J]. 中国当代医药, 2017, 24(21): 104-106转115.
YANG Feng. Effects and mechanisms of TERT modified bone marrow mesenchymal stem cells transplantation on autophagy and cognitive function in TBI rats. 中国当代医药, 2017, 24(21): 104-106转115.

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http://dangdaiyiyao.com/CN/ 或 http://dangdaiyiyao.com/CN/Y2017/V24/I21/104

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