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| Effects and mechanisms of TERT modified bone marrow mesenchymal stem cells transplantation on autophagy and cognitive function in TBI rats |
| YANG Feng |
| Department of Neurosurgery,the Sixth People′s Hospital of Chongqing,Chongqing400060,China |
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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.
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