中国组织工程研究

中国组织工程研究 ›› 2017, Vol. 21 ›› Issue (25): 4020-4025.doi: 10.3969/j.issn.2095-4344.2017.25.014

• 干细胞移植 stem cell transplantation • 上一篇    下一篇

小剂量雌激素肌肉注射联合骨髓间充质干细胞移植修复脊髓损伤

康 聪1，孟宪勇2，杨新明2，成垚昱1，张振梁1   

  1. 1河北北方学院，河北省张家口市  075000；2河北北方学院附属第一医院，河北省张家口市  075000
  • 修回日期:2017-03-20 出版日期:2017-09-08 发布日期:2017-10-09
  • 通讯作者: 孟宪勇，副主任医师，河北北方学院附属第一医院骨科，河北省张家口市 075000
  • 作者简介:康聪，男，1988年生，河北省衡水市人，汉族，河北北方学院在读硕士，主要从事脊柱外科方向研究。
  • 基金资助:

    河北省卫生厅2011年医学科学研究重点项目计划(20110176)：BMSC体外分化移植治疗脊髓损伤临床与基础研究

Combined use of low-dose 17-beta estradiol and bone marrow mesenchymal stem cell transplantation for spinal cord repair

Kang Cong1, Meng Xian-yong2, Yang Xin-ming2, Cheng Yao-yu1, Zhang Zhen-liang1   

  1. 1Hebei North University, Zhangjiakou 075000, Hebei Province, China; 2Department of Orthopedics, the First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei Province, China
  • Revised:2017-03-20 Online:2017-09-08 Published:2017-10-09
  • Contact: Meng Xian-yong, Associate chief physician, Department of Orthopedics, the First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei Province, China
  • About author:Kang Cong, Studying for master’s degree, Hebei North University, Zhangjiakou 075000, Hebei Province, China
  • Supported by:

    the Medical Research Project of Hebei Provincial Health Department in 2011, No. 20110176

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文题释义：
骨髓间充质干细胞移植治疗脊髓损伤的机制：骨髓间充质干细胞局部移植到相应受损脊髓节段不但能够长期存活，而且向神经元和胶质细胞分化起到一种“网架”的作用，支持和引导神经轴突的生长和再生。骨髓间充质干细胞除了在损伤局部发挥替代作用以外，还可直接调节脊髓损伤部位的微环境，迁移至损伤处的骨髓间充质干细胞可自分泌和(或)旁分泌脑源性神经营养因子、神经生长因子、血管内皮生长因子等多种神经保护性营养因子，这些因子表达上调，可促进局部微血管再生、神经再生和重构，修复损伤细胞。

 

摘要
背景：多种手段联合应用可针对不同靶点进行有效干预，发挥叠加或协同作用，已成为当前脊髓损伤治疗的新思路。
目的：探讨骨髓间充质干细胞移植联合应用小剂量雌激素对大鼠脊髓损伤后神经功能恢复及炎症反应的影响。  
方法：将70只雄性SD大鼠随机分5组，假手术组(n=10)仅暴露脊髓，不做损伤处理；模型组、雌激素组、干细胞组、联合组(每组15只)采用改良的Allen’s法建立脊髓损伤模型。干细胞组、联合组造模后立即在损伤部位移植骨髓间充质干细胞；雌激素组、联合组造模后第1，24小时肌肉注射17β-雌二醇。造模后第1，3，5，7天，进行BBB行为学评价；造模后6，12，24，72 h，应用ELISA法测定脊髓匀浆组织白细胞介素1β、肿瘤坏死因子α水平，TUNEL染色观察脊髓组织切片神经细胞凋亡情况。
结果与结论：①与假手术组比较，模型组造模后不同时间点的BBB行为学评分下降(P < 0.05)；与模型组比较，干细胞、雌激素组、联合组造模后5，7 d的BBB行为学评分升高(P < 0.05)，且联合组高于干细胞、雌激素组(P < 0.05)；②与假手术组比较，模型组造模后6，12，24 h的白细胞介素1β、肿瘤坏死因子α水平升高(P < 0.05)；与模型组比较，干细胞、雌激素组、联合组造模后12，24 h的白细胞介素1β、肿瘤坏死因子α水平降低(P < 0.05)，且联合组低于干细胞、雌激素组(P < 0.05)；③造模后72 h，模型组神经细胞凋亡率高于假手术组，干细胞、雌激素组、联合组低于模型组(P < 0.05)，且以联合组最低(P < 0.05)；④结果表明在脊髓损伤中，雌激素与骨髓间充质干细胞联合应用具有协同作用，能更有效抑制神经细胞凋亡，促进脊髓功能恢复。

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程
ORCID: 0000-0002-1663-9429(孟宪勇)

关键词: 干细胞, 移植, 脊髓损伤, 雌激素, 骨髓间充质干细胞, 白细胞介素1β, 肿瘤坏死因子α, 细胞凋亡, 细胞移植

Abstract:

BACKGROUND: Combined use of multiple interventions for different targets play superimposed or synergistic effects, which has become the current idea for spinal cord injury treatment.
OBJECTIVE: To investigate the synergistic effects of low doses of 17-β estradiol combined with bone marrow mesenchymal stem cells (BMSCs) transplantation on the recovery of motor function and inflammatory reactions after spinal cord injury in rats. 
METHODS: The 10 of 70 male Sprague-Dawley rats served as sham group in which the spinal cord was only exposed but with no treatment, and the rest 60 rats were used to make animal models of spinal cord injury using modified Allen’s method and then randomized into four groups (n=15 per group): model, estrogen, stem cell and combined treatment groups. Rats in the stem cell and combined treatment groups were given BMSCs transplantation at injured side; rats in the estrogen and combined treatment groups were given intramuscular injection of 17-β estradiol at 1 and 24 hours after modeling. At 1, 3, 5 and 7 days after modeling, rat functional recovery was evaluated by the Basso, Beatlie, Bresnahan score. The expressions of interleukin-1β and tumor necrosis factor-α in the injured spinal cord were detected by ELISA at 6, 12, 24, and 72 hours after modeling. Apoptosis in nerve cells was observed using TUNEL staining. 
RESULTS AND CONCLUSION: The Basso, Beatlie, Bresnahan scores were declined significantly after modeling, increased at 5 and 7 days after stem cell transplantation, estrogen treatment or their combined treatment (P < 0.05), especially in the combined treatment group (P < 0.05). The levels of interleukin-1β and tumor necrosis factor-α were elevated gradually after spinal cord injury (P < 0.05), but the levels decreased significantly at 12 and 24 hours in stem cell, estrogen and combined treatment groups (P < 0.05), and this decrease trend was more significant in the combined treatment group compared with the stem cell and estrogen groups (P < 0.05). At 72 hours after modeling, the rate of TUNEL positive cells was highest in the model group (P < 0.05) and lowest in the combined treatment group (P < 0.05). To conclude, the combined use of low doses of 17-β estradiol and BMSCs transplantation can facilitate the recovery of motor function after spinal cord injury by effectively inhibiting apoptosis in nerve cells.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Mesenchymal Stem Cells, Spinal Cord Injuries, Estrogens, Tissue Engineering

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