切换至 "中华医学电子期刊资源库"

中华神经创伤外科电子杂志 ›› 2015, Vol. 01 ›› Issue (05) : 25 -29. doi: 10.3877/cma.j.issn.2095-9141.2015.05.007

所属专题: 文献

基础研究

骨髓间充质干细胞移植对血管性痴呆大鼠认知功能的影响
黑悦1, 樊才瑞2, 龙乾发3, 罗强3, 魏礼洲1, 伊西才1, 刘卫平1,()   
  1. 1. 710032 西安,第四军医大学西京医院神经外科
    2. 571100 海口,解放军第187医院神经外科
    3. 710003 西安,西安市中心医院神经外科
  • 收稿日期:2015-05-11 出版日期:2015-10-15
  • 通信作者: 刘卫平
  • 基金资助:
    陕西省科技统筹基金资助项目(2013KTCL03-08)

The effect of bone marrow mesenchymal stem cells transplantation on the cognitive ability in a rat model of vascular dementia

Yue Hei1, Cairui Fan2, Qianfa Long3, Qiang Luo3, Lizhou Wei1, Xicai Yi1, Weiping Liu1,()   

  1. 1. Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
    2. Department of Neurosurgery, 187th Hospital of PLA, Haikou 571100, China
    3. Department of Neurosurgery, Xi’an central hospital, Xi’an Jiao Tong University, Xi’an 710003, China
  • Received:2015-05-11 Published:2015-10-15
  • Corresponding author: Weiping Liu
  • About author:
    Corresponding author: Liu Weiping, Email:
引用本文:

黑悦, 樊才瑞, 龙乾发, 罗强, 魏礼洲, 伊西才, 刘卫平. 骨髓间充质干细胞移植对血管性痴呆大鼠认知功能的影响[J/OL]. 中华神经创伤外科电子杂志, 2015, 01(05): 25-29.

Yue Hei, Cairui Fan, Qianfa Long, Qiang Luo, Lizhou Wei, Xicai Yi, Weiping Liu. The effect of bone marrow mesenchymal stem cells transplantation on the cognitive ability in a rat model of vascular dementia[J/OL]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2015, 01(05): 25-29.

目的

探究骨髓间充质干细胞(BMSCs)移植对血管性痴呆大鼠认知功能及海马CA1区域GAD67、GABABR1的表达的影响。

方法

成年雄性SD大鼠60只随机分为假手术组(n=20),模型组(n=20)和移植组(n=20)。结扎双侧颈总动脉建立大鼠血管性痴呆模型,2 h后BMSCs尾静脉移植,28 d后水迷宫检测认知变化,Western blotting和免疫组化分析大鼠海马CA1区GAD67和GABABR1的表达变化。

结果

(1)Western blotting和免疫组化结果显示,模型组相比假手术组在慢性期海马CA1区GAD67和GABABR1表达水平(蛋白水平以及免疫组化染色强度)下调,差异具有统计学意义(分别为1.347±0.357比2.237±0.956,t=5.478,P=0.0076;0.779±0.181比1.691±0.337,t=4.893,P=0.0073)。(2)移植组GAD67和GABABR1表达水平改变均比模型组轻微,差异具有统计学意义(分别为1.611±1.007比1.347±0.357,t=2.379,P=0.0373;1.009±0.257比0.779±0.181,t=2.678,P=0.0441)。(3)水迷宫认知功能测试显示,移植组比模型组潜伏期缩短(20.817±2.891比30.192±3.472,t=2.743,P=0.0442),且在游泳轨迹方面显示出更好的方向性。

结论

BMSCs移植可提升血管性痴呆大鼠认知功能并上调海马CA1区GAD67和GABABR1表达水平。

Objective

To investigate the effect of bone marrow mesenchymal stem cells (BMSCs) transplantation on bilateral common carotid artery occlusion (2VO)-induced cognitive impairments and expression of GAD67 and GABABR1 in the hippocampal CA1 subfield.

Methods

60 adult male SD rats were randomly divided into Sham group (n=20), group (n=20) and BMSCs group (n=20). BMSCs transplantation was performed 2 h after the surgery of 2VO. After 28 days, Morris Water Maze (MWM) test was performed to investigate the cognitive changes, and Western blot and immunohistochemistry were used to evaluate the expression of GAD67 and GABABR1 in the hippocampal CA1 subfield.

Results

(1)Western blot and immunohistochemistry showed that compared to sham group, the expression of GAD67 and GABABR1 (protein level and the intensity of immunohistochemical staining) lowered(1.347±0.357 vs. 2.237±0.956, t=5.478, P=0.0076; 0.779±0.181 vs. 1.691±0.337, t=4.893, P=0.0073, respectively). (2)while BMSCs transplants partly reversed these changes(1.611±1.007 vs. 1.347±0.357, t=2.379, P=0.0373; 1.009±0.257 vs. 0.779±0.181, t=2.678, P=0.0441, respectively). (3)MWM also showed that cognitive ability in the BMSCs group improved significantly (20.817±2.891 vs. 30.192±3.472, t=2.743, P=0.0442) compared to VaD group.

Conclusion

BMSCs transplantation could improve the expression of GAD67 and GABABR1 in the hippocampal CA1 subfield and restore the cognitive ability in a rat model of vascular dementia.

图1 大鼠水迷宫实验的逃避潜伏期
图2 大鼠水迷宫实验的游泳轨迹
图3 GAD67和GABABR1的免疫组化染色结果
图4 GAD67和GABABR1的Western blot结果
[1]
Iadecola C. The pathobiology of vascular dementia[J]. Neuron, 2013, 80(4): 844-866.
[2]
Soares LM, Schiavon AP, Milani H, et al. Cognitive impairment and persistent anxiety-related responses following bilateral common carotid artery occlusion in mice[J]. Behav Brain Res, 2013, 249(7): 28-37.
[3]
Jiwa NS, Garrard P, Hainsworth AH. Experimental models of vascular dementia and vascular cognitive impairment: a systematic review[J]. J Neurochem, 2010, 115(4): 814-828.
[4]
Xi Y, Wang M, Zhang W, et al. Neuronal damage, central cholinergic dysfunction and oxidative damage correlate with cognitive deficits in rats with chronic cerebral hypoperfusion[J]. Neurobiol Learn Mem, 2014, 109(3): 7-19.
[5]
Mao X, Ji C, Sun C, et al. Topiramate attenuates cerebral ischemia/reperfusion injury in gerbils via activating GABAergic signaling and inhibiting astrogliosis[J]. Neurochem Int, 2012, 60(1): 39-46.
[6]
Cullen PK, Dulka BN, Ortiz S, et al. GABA-mediated presynaptic inhibition is required for precision of long-term memory[J]. Learn Mem, 2014, 21(4): 180-184.
[7]
Li CJ, Lu Y, Zhou M, et al. Activation of GABAB receptors ameliorates cognitive impairment via restoring the balance of HCN1/HCN2 surface expression in the hippocampal CA1 area in rats with chronic cerebral hypoperfusion[J]. Mol Neurobiol, 2014, 50(2): 704-720.
[8]
Caputi A, Melzer S, Michael M, et al. The long and short of GABAergic neurons[J]. Curr Opin in Neurobiol, 2013, 23(2): 179-186.
[9]
Lu Y, Li C, Zhou M, et al. Clonidine ameliorates cognitive impairment induced by chronic cerebral hypoperfusion via up-regulation of the GABABR1 and GAD67 in hippocampal CA1 in rats[J]. Pharmacol Biochem Behav, 2015, 132(1): 96-102.
[10]
Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke, 1989, 20(1): 84-91.
[11]
Loreth D, Ozmen L, Revel FG, et al. Selective degeneration of septal and hippocampal GABAergic neurons in a mouse model of amyloidosis and tauopathy[J]. Neurobiol Dis, 2012, 47(1): 1-12.
[12]
Li G, Bien-Ly N, Andrews-Zwilling Y, et al. GABAergic interneuron dysfunction impairs hippocampal neurogenesis in adult apolipoprotein E4 knockin mice[J]. Cell Stem Cell, 2009, 5(6): 634-645.
[13]
Wang J, Fu X, Jiang C, et al. Bone marrow mononuclear cell transplantation promotes therapeutic angiogenesis via upregulation of the VEGF-VEGFR2 signaling pathway in a rat model of vascular dementia[J]. Behav Brain Res, 2014, 265(5): 171-180.
[14]
樊才瑞,刘卫平,龙乾发,等.骨髓间充质干细胞对血管性痴呆大鼠的保护作用[J].中华神经外科疾病研究杂志, 2015(2): 146-149.
[15]
王昌铭,李华信,姚永杰,等. BMSCs颈内动脉移植在VD大鼠脑内存活迁移及其对海马细胞凋亡的影响[J].免疫学杂志, 2014(3): 215-219.
[16]
井沆,田茂,董艳军,等.骨髓间充质干细胞移植对血管性痴呆大鼠认知功能及一氧化氮合酶的表达的影响[J].临床神经病学杂志, 2015(4): 276-280.
[17]
Taguchi A. Cell-based therapy for patients with vascular dementia[J]. Psychogeriatrics, 2011, 11(2): 113-115.
[18]
Long Q, Qiu B, Wang K, et al. Genetically engineered bone marrow mesenchymal stem cells improve functional outcome in a rat model of epilepsy[J]. Brain Res, 2013, 1532(3): 1-13.
[19]
Wang K, Long Q, Jia C, et al. Over-expression of Mash1 improves the GABAergic differentiation of bone marrow mesenchymal stem cells in vitro[J]. Brain Res Bull, 2013, 99(10): 84-94.
[20]
Mauri M, Lentini D, Gravati M, et al. Mesenchymal stem cells enhance GABAergic transmission in co-cultured hippocampal neurons[J]. Mol Cell Neurosci, 2012, 49(4): 395-405.
[1] 何甘霖, 陈香侬, 李萍, 甄佳怡, 李京霞, 邹外一, 许多荣. 白血病异基因造血干细胞移植术后股骨坏死的影响因素[J/OL]. 中华关节外科杂志(电子版), 2024, 18(04): 450-456.
[2] 刘云, 时月, 郭冬梅, 邱志远, 王丽娟, 冉学红, 李乾鹏. 造血干细胞移植治疗伴有胚系突变的髓系肿瘤患者三例并文献复习[J/OL]. 中华移植杂志(电子版), 2024, 18(04): 230-234.
[3] 刘麾, 赵鹏, 冯静, 胡晓彦, 杜涛, 王凌云. 三维调强放射治疗对急性髓系白血病异基因造血干细胞移植后髓外复发的疗效观察[J/OL]. 中华移植杂志(电子版), 2024, 18(02): 110-115.
[4] 朴美英, 刘娜, 孟繁峥, 李春艳. 支气管镜诊断儿童造血干细胞移植后闭塞性细支气管炎综合征二例[J/OL]. 中华移植杂志(电子版), 2024, 18(02): 116-119.
[5] 李赞, 许芝彬, 冯志金, 张雄. 重型β-地中海贫血患儿异基因造血干细胞移植后淋巴细胞亚群动态分析[J/OL]. 中华移植杂志(电子版), 2024, 18(01): 22-29.
[6] 孔欣, 宋宝全, 刘吟, 张剑, 仇惠英, 吴德沛. 异基因造血干细胞移植并发难治性呃逆一例[J/OL]. 中华移植杂志(电子版), 2023, 17(04): 253-255.
[7] 邓瑞锋, 程璐, 周宇林, 刘远灵, 江文聪, 江敏耀, 江福能, 习明. TGF-β1诱导骨髓间充质干细胞外泌体分泌miR-424-3p促进前列腺癌细胞增殖及转移[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(01): 82-89.
[8] 王向丽, 吴涛, 毛东锋, 刘恒, 刘文慧, 周芮, 田红娟. 异基因造血干细胞移植治疗ANKRD26相关性血小板减少症1例并文献复习[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(04): 236-238.
[9] 杨阳, 王琤, 周文土, 周冰. Caveolae/Caveolin-1与膜胆固醇共同调控小鼠BMSCs成骨分化[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(03): 137-142.
[10] 刘洋, 吴涛, 刘恒, 刘文慧, 田红娟, 周芮, 高铭敏, 王向丽, 张睿. 异基因造血干细胞移植治疗CSF3R基因突变急性髓系白血病M2型1例并文献复习[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(02): 90-92.
[11] 詹卓, 晋佩佩, 张建敏, 何莉. 自体干细胞移植治疗POEMS综合征3例[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(01): 27-29.
[12] 刘文慧, 吴涛, 张曦. 间充质干细胞联合血小板生成素受体激动剂在异基因造血干细胞移植后血小板恢复中的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2023, 13(04): 242-246.
[13] 李芸芸, 吴涛, 毛东锋, 鱼玲玲, 刘文慧. 轻型β-地中海贫血供者异基因造血干细胞移植治疗重型再生障碍性贫血1例[J/OL]. 中华细胞与干细胞杂志(电子版), 2023, 13(02): 84-86.
[14] 刘然然, 方倩倩, 唐泽文. 周围神经损伤对骨髓间充质干细胞增殖及成骨分化影响的研究[J/OL]. 中华神经创伤外科电子杂志, 2023, 09(01): 7-11.
[15] 汪鹏飞, 程莹莹, 赵海康. 骨髓间充质干细胞改善神经病理性疼痛的机制探讨[J/OL]. 中华脑科疾病与康复杂志(电子版), 2024, 14(04): 230-234.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?