重组人促红细胞生成素改善小鼠创伤性脑损伤神经功能

基础医学与临床 ›› 2020, Vol. 40 ›› Issue (3): 289-293.

• 研究论文 • 下一篇

重组人促红细胞生成素改善小鼠创伤性脑损伤神经功能

吴晨瑞, 何虹兵, 程予琦, 毛岚田, 廖正步^*

重庆医科大学附属第一医院神经外科, 重庆 400016

收稿日期:2019-04-12 修回日期:2019-07-12 出版日期:2020-03-05 发布日期:2020-03-02
通讯作者: ^*liaozhengbu@hotmail.com
基金资助:
国家自然科学基金(81771355);重庆市自然科学基金(cstc2015jcyjA0526)

Recombinant human erythropoietin improves neurological function after traumatic brain injury of mice

WU Chen-rui, HE Hong-bing, CHENG Yu-qi, MAO Lan-tian, LIAO Zheng-bu^*

Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China

Received:2019-04-12 Revised:2019-07-12 Online:2020-03-05 Published:2020-03-02
Contact: ^*liaozhengbu@hotmail.com

摘要/Abstract

摘要： 目的探讨重组人促红细胞生成素(rhEPO)对小鼠创伤性脑损伤(TBI)血管生成及神经功能恢复的影响。方法将小鼠随机分为假手术组(sham组)、模型组(TBI组,控制性皮质撞击制作重型TBI模型)和治疗组[EPO组,损伤后连续7 d腹腔注射5 000 IU/(kg·d) rhEPO],每组小鼠15只。伤后3、7和14 d进行神经功能缺损评分(mNSS),14 d以Western blot及免疫荧光法检测脑损伤灶周边区域eNOS、VEGF和CD31 蛋白表达,并通过CD31⁺细胞进行微血管密度计数(MVD);21 d以苏木精-伊红(HE)染色大脑切片并检测损伤灶体积。结果伤后3、7及14 d,TBI组较sham组mNSS明显上升(P＜0.001),伤后7 及14 d EPO组mNSS低于TBI组(P＜0.05)。伤后14 d,损伤灶周边区eNOS、VEGF和CD31蛋白的表达,TBI组较sham组升高(P＜0.05),EPO组较TBI组升高 (P＜0.05);TBI组的MVD显著低于sham组(P＜0.001),EPO组的MVD显著高于TBI组(P＜0.001)。伤后21 d EPO组较TBI组创伤体积减小(P＜0.05)。结论 rhEPO促进小鼠TBI血管生成,改善颅脑损伤后神经功能。

关键词: 促红细胞生成素, 创伤性脑损伤, 血管生成, eNOS, VEGF

Abstract: Objective To investigate the effects of recombinant human erythropoietin (rhEPO) on angiogenesis and neurofunction recovery of mice with traumatic brain injury(TBI). Methods Mice were randomly divided into sham operation group (sham group), traumatic brain injury group (TBI group, severe TBI model made by controlled cortical impact) and rhEPO treatment group (EPO group, rhEPO intraperitoneal injected at 5 000 IU/(kg·d) for 7 days after the trauma). Each group included 15 mice. Neurological scores were performed at 3, 7, and 14 d using modified neurological severity score(mNSS). Fourteen days after injury, Western blot and immunofluorescence were used to detect the protein expression of eNOS, VEGF and CD31 around ipsilateral cerebral cortex, and the microvessel density (MVD) was detected by CD31⁺ cells. The lesion volume was measured at 21 d after injury using hematoxylin-eosin (HE) stained specimens. Results 3,7 and 14 d after TBI, mNSS of TBI group was signifi- cantly higher than that of sham group (P＜0.001). 7 and 14 d after TBI, mNSS of EPO group was lower than those of TBI group (P＜0.05). Fourteen days after TBI, the protein expression of eNOS, VEGF and CD31 was higher in TBI group than those of sham group, and the EPO group was higher than those of TBI group. (P＜0.05). 14 d after TBI, the MVD of TBI group was significantly lower than sham group(P＜0.001), and the MVD of EPO group was significantly higher than TBI group(P＜0.001). Twenty one days after injury, the volume of EPO group was reduced compared with TBI group (8.90±1.79) (P＜0.05). Conclusions rhEPO promotes angiogenesis and improves neurological function after TBI of mice.

Key words: erythropoietin, traumatic brain injury, angiogenesis, eNOS, VEGF

中图分类号:

R651.1

吴晨瑞, 何虹兵, 程予琦, 毛岚田, 廖正步. 重组人促红细胞生成素改善小鼠创伤性脑损伤神经功能[J]. 基础医学与临床, 2020, 40(3): 289-293.

WU Chen-rui, HE Hong-bing, CHENG Yu-qi, MAO Lan-tian, LIAO Zheng-bu. Recombinant human erythropoietin improves neurological function after traumatic brain injury of mice[J]. Basic & Clinical Medicine, 2020, 40(3): 289-293.

参考文献

[1]Pearn ML, Niesman IR, Egawa J, et al. Pathophysiology associated with traumatic brain injury: current treatments and potential novel therapeutics[J]. Cell Mol Neurobiol, 2017, 37: 571-585.
[2]Robinson S, Winer JL, Chan LAS, et al. Extended erythropoietin treatment prevents chronic executive functional and microstructural deficits following early severe traumatic brain injury in rats[J]. Front Neurol, 2018,9:451. doi:10.3389/fneur.2018.00451
[3]Gantner DC, Bailey M, Presneill J, et al. Erythropoietin to reduce mortality in traumatic brain injury: a post-hoc dose-effect analysis[J]. Ann Surg, 2018,267:585-589.
[4]Li ZM, Xiao YL, Zhu JX, et al. Recombinant human erythropoietin improves functional recovery in patients with severe traumatic brain injury: A randomized, double blind and controlled clinical trial[J]. Clin Neurol Neurosurg, 2016,150:80-83.
[5]Ma X, Aravind A, Pfister BJ, et al. Animal models of traumatic brain injury and assessment of injury severity[J]. Mol Neurobiol, 2019, 56(8): 5332-5345
[6]Behrouzifar S, Vakili A, Bandegi AR. Neuroprotective nature of adipokine resistin in the early stages of focal cerebral ischemia in a stroke mouse model[J]. Neurochem Int,2018,114:99-107.
[7]Siddiq I, Park E, Liu E, et al. Treatment of traumatic brain injury using zinc-finger protein gene therapy target-ing VEGF-A[J]. J Neurotraum,2012,29:2647-2659.
[8]Annese T, Tamma R, Ruggieri S. Erythropoietin in tumor angiogenesis[J]. Exp Cell Res,2019,374:266-273.
[9]Che X, Fang Y, Si X, et al. The role of gaseous molecules in traumatic brain injury: an updated review[J]. Front Neurosci,2018,12:392. doi: 10.3389/fnins.2018.00392.
[10]Hers I, Vincent EE. Akt signalling in health and disease[J]. Cell Signal,2011,23:1515-1527.
[11]Thau-Zuchman O, Shohami E, Alexandrovich AG. Subacute treatment with vascular endothelial growth factor after traumatic brain injury increases angiogenesis and gliogenesis[J]. Neurosci,2012,202:334-341.
[12]Sköld MK, Risling M. Inhibition of vascular endothelial growth factor receptor 2 activity in experimental brain contusions aggravates injury outcome and leads to early increased neuronal and glial degeneration[J]. Eur J Neurosci,2006,23:21-34.
[13]Zhou S, Yin DP, Wang Y, et al. Dynamic changes in growth factor levels over a 7-day period predict the functional outcomes of traumatic brain injury[J]. Neural Regen Res,2018,13:2134-2140.
[14]Krum JM, Mani N. Angiogenic and astroglial responses to vascular endothelial growth factor administration in adult rat brain[J]. Neurosci,2002,110:589-604.

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重组人促红细胞生成素改善小鼠创伤性脑损伤神经功能

Recombinant human erythropoietin improves neurological function after traumatic brain injury of mice

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