中国组织工程研究

中国组织工程研究 ›› 2020, Vol. 24 ›› Issue (8): 1238-1242.doi: 10.3969/j.issn.2095-4344.1975

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

8-羟基-2-(二丙基氨基)四氢萘干预弥漫性轴索损伤模型大鼠低氧诱导因子1α的表达

毛振立1，宋振全2，张海松2，刘恩智3   

  1. 1朝阳市中心医院神经外科，辽宁省朝阳市  122000；2北部战区总医院神经外科，辽宁省沈阳市 110016；3抚顺市中心医院神经外科，辽宁省抚顺市  113006
  • 收稿日期:2019-04-22 修回日期:2019-04-30 接受日期:2019-06-12 出版日期:2020-03-18 发布日期:2020-01-22
  • 通讯作者: 宋振全，博士，主任医师，教授，北部战区总医院神经外科，辽宁省沈阳市 110016
  • 作者简介:毛振立，男，1983年生，河北省任县人，汉族，2013年辽宁医学院毕业，硕士，主治医师，主要从事脑损伤及脑血管病相关研究。

Effect of 8-hydroxy-2-(di-n-propylamino)tetralin on hypoxia inducible factor 1 alpha expression following diffuse axonal injury in rats  

Mao Zhenli1, Song Zhenquan2, Zhang Haisong2, Liu Enzhi3   

  1. 1Department of Neurosurgery, Chaoyang Central Hospital, Chaoyang 122000, Liaoning Province, China; 2Department of Neurosurgery, General Hospital of Northern Theater Command, Shenyang 110016, Liaoning Province, China; 3Department of Neurosurgery, Fushun Central Hospital, Fushun 113006, Liaoning Province, China
  • Received:2019-04-22 Revised:2019-04-30 Accepted:2019-06-12 Online:2020-03-18 Published:2020-01-22
  • Contact: Song Zhenquan, MD, Chief physician, Professor, Department of Neurosurgery, General Hospital of Northern Theater Command, Shenyang 110016, Liaoning Province, China
  • About author:Mao Zhenli, Master, Attending physician, Department of Neurosurgery, Chaoyang Central Hospital, Chaoyang 122000, Liaoning Province, China

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摘要：

文题释义：
8-羟基-2-(二丙基氨基)四氢萘(8-hydroxy-2-(di-n-propylamino)tetralin，8-OH-DPAT)：是五羟色胺1A (5-HTlA)受体激动剂的一种，长久以来一直做为抗精神类药物被广泛研究，其在减轻焦虑和抑郁症的治疗作用的机制已经有据可查，除此以外，5-HTlA受体激动剂仍具有降低体温及神经保护作用。
脑弥漫性轴索损伤(diffuse axonal injury，DAI)：是头部遭受加速性旋转外力作用时，因剪应力造成的以脑内神经轴索肿胀断裂为主要特征的损伤。一般认为，当头部加速运动时，脑组织因受瞬时产生的剪力和张力作用而发生应变，使神经轴索、毛细血管和小血管损伤。弥漫性轴索损伤好发于神经轴索聚集区，如胼胝体、脑干头端背外侧、大脑半球的灰质和白质交界处、小脑、内囊、基底节核团附近及透明隔等处。

背景：8-羟基-2-(二丙基氨基)四氢萘(8-hydroxy-2-(di-n-propylamino)tetralin，8-OH-DPAT)具有降低脑温的作用，且此作用可能是其发挥神经保护作用的潜在机制之一。

目的：观察8-OH-DPAT对弥漫性轴索损伤大鼠脑组织低氧诱导因子1α表达的影响，探讨8-OH-DPAT对弥漫性轴索损伤大鼠神经保护作用的途径。

方法：实验方案经北部战区动物实验伦理委员会批准。将Wistar大鼠随机分为4组：模型组(n=35)、恒温组(n=35)、8-OH-DPAT组(n=35)和正常组(n=7)。除正常组外，其他各组均参照Marmarou法制作弥漫性轴索损伤模型，恒温组和8-OH-DPAT组建模成功后腹腔注射8-OH-DPAT，模型组和正常组腹腔注射生理盐水；恒温组用恒温毯维持体温(37.0±0.5) ℃。每隔1 h测量大鼠脑温。分别于弥漫性轴索损伤后6，12，24，72， 168 h观察大鼠脑组织的损伤程度以及血清和损伤脑组织中低氧诱导因子1α的表达。

结果与结论：①造模后1 h，与恒温组和模型组比较，8-OH-DPAT组大鼠脑温明显下降(P < 0.05)，至造模后2 h降至最低(P < 0.05)，之后缓慢上升；②苏木精-伊红染色显示，模型组大鼠脑组织损伤最为严重，恒温组次之，8-OH-DPAT组损伤最轻；③免疫组织化学和ELISA结果显示，正常组血清及脑组织低氧诱导因子1α表达很低；弥漫性轴索损伤后6 h，模型组血清及脑组织低氧诱导因子1α表达增多，24 h达高峰，之后逐渐减少；与模型组比较，恒温组和8-OH-DPAT组对应时间点血清及脑组织低氧诱导因子1α表达明显减少(P < 0.05或P < 0.01)，8-OH-DPAT组减少更明显(P < 0.01)；④结果说明，8-OH-DPAT对弥漫性轴索损伤大鼠脑组织的神经保护作用与其降低大鼠脑温，减少损伤脑组织低氧诱导因子1α的表达有关。

ORCID: 0000-0002-4637-3553(毛振立)

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: 8-羟基-2-(二丙基氨基)四氢萘, 弥漫性轴索损伤, 亚低温, 低氧诱导因子1α, 神经保护

Abstract:

BACKGROUND: 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) can decrease brain temperature, which is the potential mechanism of its neuroprotection.

OBJECTIVE: To investigate the effect of 8-OH-DPAT on hypoxia inducible factor 1α in the brain tissue of rats with diffuse axonal injury, and to explore the underlying mechanism of 8-OH-DPAT exerting neuroprotection in rats of diffuse axonal injury.

METHODS: The study was approved by the Laboratory Animal Ethical Committee of General Hospital of Northern Theater Command. Wistar rats were randomly assigned into four groups: model group (n=35), constant temperature group (n=35), 8-OH-DPAT group (n=35) and normal group (n=7). Excepting the normal group, rat models of diffuse axonal injury were established according to Marmarou method. Rat models in the constant temperature and 8-OH-DPAT were intraperitoneally injected with 8-OH-DPAT, but those in the model and normal groups were intraperitoneally injected with physiological saline. The body temperature of rats in the constant temperature group was maintained at (37.0±0.5)°C using the blanket. The body temperature of rats was measured every 1 hour. Then, brain injury and hypoxia inducible factor 1α expression level were observed at 6, 12, 24, 72, and 168 hours after diffuse axonal injury in rats.

RESULTS AND CONCLUSION: (1) Compared with the constant temperature and model groups, brain temperature was significantly lower in the 8-OH-DPAT group at 1 hour following modeling (P < 0.05), became lowest at 2 hours (P < 0.05), and then gradually increased. (2) Hematoxylin-eosin staining results revealed that brain injury was more serious in the model group, followed by constant temperature group, and lightest in the 8-OH-DPAT group. (3) Results of immunohistochemistry and ELISA showed that the expression level of hypoxia inducible factor 1α in the serum and brain tissue was lowest in the normal group. In the 8-OH-DPAT group, the expression level of hypoxia inducible factor 1α was increased at 6 hours after diffuse axonal injury, and peaked at 24 hours. Compared with the model group, the expression level of hypoxia inducible factor 1α in serum and brain tissue in the constant temperature and 8-OH-DPAT groups was significantly decreased (P < 0.05 or P < 0.01), especially the 8-OH-DPAT group (P < 0.01). (4) These results imply that 8-OH-DPAT decreases hypoxia inducible factor 1α expression in brain tissue of diffuse axonal injury rats by reducing brain temperature, alleviates the degree of nerve injury, and exerts a neuroprotective effect. 

Key words: 8-hydroxy-2-(di-n-propylamino)tetralin, diffuse axonal injury, mild hypothermia, hypoxia inducible factor 1α, neuroprotection

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