中国组织工程研究 ›› 2019, Vol. 23 ›› Issue (23): 3667-3672.doi: 10.3969/j.issn.2095-4344.1311

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

反复短暂缺血可抑制坐骨神经损伤模型大鼠失神经支配的腓肠肌萎缩

周晓彬1,王  东2,林朋朝1,高伟静1,姬艳林1,祁  欢3,李  静4,周君琳2   

  1.  (石家庄市第三医院,1创伤三科,3创伤二科,河北省石家庄市  050000;2首都医科大学附属北京朝阳医院创伤骨科,北京市  100008;4河北省老年病医院中医科,河北省石家庄市  050000)
  • 收稿日期:2019-03-23 出版日期:2019-08-18 发布日期:2019-08-18
  • 通讯作者: 周君琳,博士,主任医师,教授,首都医科大学附属北京朝阳医院创伤骨科,北京市 100008
  • 作者简介:周晓彬,女,1979年生,河北省石家庄市人,汉族, 2018年首都医科大学毕业,博士,副主任医师,副教授,主要从事周围神经损伤修复,骨与关节损失修复的研究。
  • 基金资助:

    河北省医学科学研究重点课题计划(20181060),项目负责人:周晓彬;北京市科学技术委员会(Z161100000116080),项目负责人:周君琳

Repeated transient ischemia inhibits denervated gastrocnemius atrophy in rat models of sciatic nerve injury 

Zhou Xiaobin1, Wang Dong2, Lin Pengzhao1, Gao Weijing1, Ji Yanlin1, Qi Huan3, Li Jing4, Zhou Junlin2   

  1. (1Third Department of Traumatology, 3Second Department of Traumatology, Shijiazhuang Third Hospital, Shijiazhuang 050000, Hebei Province, China; 2Department of Orthopedic Traumatology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100008, China; 4Department of Traditional Chinese Medicine, Hebei Provincial Geriatric Hospital, Shijiazhuang 050000, Hebei Province, China)
  • Received:2019-03-23 Online:2019-08-18 Published:2019-08-18
  • Contact: Zhou Junlin, MD, Chief physician, Professor, Department of Orthopedic Traumatology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100008, China
  • About author:Zhou Xiaobin, MD, Associate chief physician, Associate professor, Third Department of Traumatology, Shijiazhuang Third Hospital, Shijiazhuang 050000, Hebei Province, China
  • Supported by:

    the Hebei Provincial Key Program of Medical Science Research, No. 20181060 (to ZXB); the Science and Technology Commission of Beijing, No. Z161100000116080 (to ZJL)

摘要:

文章快速阅读:

文题释义:

反复短暂缺血:即短暂的重复缺血后,可以增强组织、器官对缺血的耐受性,可将缺血耐受形象的称为“置于死地而后生”。大自然创造了许多天然的缺血适应模型。例如在自然界中,适应极端恶劣的条件如低氧或无氧的现象本身就是耐受模型,另外,冬眠也是一种适应极度低灌注损伤的耐受现象,因此可以将缺血耐受看作是自然界进化的保守形式。
血管内皮生长因子(vascular endothelial growth factor,VEGF):是血管内皮细胞特异性的肝素结合生长因子,可在体内诱导血管新生,由于mRNA不同的剪切方式,产生出分别VEGF121、VEGF145、VEGF165、VEGF185、VEGF206等至少5种蛋白形式,其中VEGF121、VEGF145、VEGF165是分泌型可溶性蛋白,能直接作用于血管内皮细胞促进血管内皮细胞增殖,增加血管通透性。
摘要
背景
:既往实验表明反复短暂缺血可以诱导肌肉的缺血耐受,达到营养靶器官的作用。
目的:探讨反复短暂缺血对坐骨神经损伤模型大鼠失神经支配腓肠肌细胞萎缩的抑制作用。
方法:60只8周龄SD大鼠,由北京维通利华动物技术有限公司提供,实验过程得到首都医科大学动物实验伦理委员会批准(伦理号AEEI-2017-055)。随机将大鼠分为3组,实验组和对照组大鼠均建立坐骨神经损伤模型,实验组患侧下肢给予每天1次3×(10 min缺血/10 min再灌注);对照组:吻合神经后不给予反复短暂缺血处理;假手术组:未损伤神经,给予患侧肢体每天1次3×(10 min缺血/10 min再灌注)。比较2周及4周时3组间腓肠肌湿质量维持率,腓肠肌苏木精-伊红染色,坐骨神经电生理及ELISA测定腓肠肌内血管内皮生长因子的含量。
结果与结论:①电生理显示4周时实验组与对照组均未检测到腓肠肌的动作电位及潜伏期;②腓肠肌湿质量维持率检测结果显示实验组较对照组明显增加(P < 0.05),假手术组优于实验组和对照组(P < 0.01);③腓肠肌纤维横截面积结果显示实验组肌纤维化较对照组明显减轻(P < 0.05);④ELISA检测结果显示实验组及假手术组腓肠肌内血管内皮生长因子含量均显著高于对照组(P < 0.05);⑤结果说明,神经损伤后4周内,反复短暂缺血可以有效提高腓肠肌内源性血管内皮生长因子的表达,从而发挥内源性血管内皮生长因子抑制腓肠肌萎缩的作用。

关键词: 反复短暂缺血, 腓肠肌, 血管内皮生长因子, 电生理, 肌萎缩, 坐骨神经损伤, 大鼠

Abstract:

BACKGROUND: Preliminary study has shown that repeated transient ischemia may induce muscle ischemia tolerance to enrich target organs.
OBJECTIVE: To investigate the inhibitory effect of repeated transient ischemia on atrophy of denervated gastrocnemius muscle cells in a rat model of sciatic nerve injury.
METHODS: Sixty Sprague-Dawley rats aged 8 weeks were provided by Beijing Weitong Lihua Animal Technology Co., Ltd., and the study was approved by the Laboratory Animal Ethics Committee of Capital Medical University, approval number: AEEI-2017-055. The rats were randomly divided into control group (sciatic nerve injury model), experimental group (sciatic nerve injury model plus 3x(10-minute ischemia/10-minute reperfusion) and sham group [3x(10-minute ischemia/10-minute reperfusion)]. The wet mass maintenance rate of gastrocnemius, hematoxylin-eosin staining of gastrocnemius, electrophysiology of sciatic nerve, and content of vascular endothelial growth factor in gastrocnemius detected by ELISA were compared among groups at 2 and 4 weeks. 
RESULTS AND CONCLUSION: (1) Electrophysiology showed that neither experimental nor control groups presented action potential or latency at 4 weeks. (2) The wet mass maintenance rate of gastrocnemius in the experimental group was significantly increased compared with the control group (P < 0.05), and the sham group was significantly superior to the experimental and control groups (P < 0.01). (3) The cross-sectional area of gastrocnemius fibers in the experimental group was significantly decreased compared with the control group (P < 0.05). (4) The content of vascular endothelial growth factor in gastrocnemius detected by ELISA in the experimental and sham groups was significantly higher than that in the control group (P < 0.05). (5) These results suggest that within 4 weeks of nerve injury, the repeated transient ischemia can effectively improve the expression of endogenous vascular endothelial growth factor in gastrocnemius, thus inhibiting its atrophy.

Key words:  repeated transient ischemia, gastrocnemius, vascular endothelial growth factor, electrophysiology, muscle atrophy, sciatic nerve injury, rats

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