依达拉奉干预永久性脑缺血大鼠神经干细胞增殖及分化

梁晓艳

doi:10.16098/j.issn.0529-1356.2021.03.007

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解剖学报 ›› 2021, Vol. 52 ›› Issue (3) : 370-376. DOI: 10.16098/j.issn.0529-1356.2021.03.007

神经生物学

依达拉奉干预永久性脑缺血大鼠神经干细胞增殖及分化

梁晓艳¹ 顾玉²赵梦¹ 杜鑫¹ 刘宏伟¹周洋¹ 张铁军^3*

作者信息 +

Edaravone intervening the proliferation and differentiation of neural stem cells in rats with permanent cerebral ischemia

LIANG Xiao-yan¹ GU Yu² ZHAO Meng¹ DU Xin1 LIU Hong-wei¹ZHOU Yang¹ ZHANG Tie-jun^3*

Author information +

文章历史 +

摘要

目的探讨依达拉奉对永久性脑缺血大鼠脑内内源性神经干细胞的影响。方法采用电凝法建立大鼠永久性脑缺血模型。将30只SD大鼠随机分为假手术组、脑损伤组与依达拉奉组，每组10只，模型制作成功后6 h，1.5 g/L依达拉奉组腹腔注射依达拉奉（10 ml/kg），每天1次，假手术组与脑缺血组腹腔注射等体积的生理盐水，连续注射7 d。末次给药后24 h，免疫荧光染色观察损伤侧脑室下区与缺血周围脑皮质区BrdU标记阳性细胞、Nestin/BrdU标记阳性细胞、神经元Ⅲ型β-微管蛋白（Tuj1）/BrdU标记阳性细胞与胶质纤维酸性蛋白（GFAP）/BrdU标记阳性细胞，Western blotting 检测缺血周围脑皮质区Tuj1与GFAP蛋白表达。结果与脑缺血组比较，依达拉奉组损伤侧脑室下区与缺血周围脑皮质区的BrdU标记阳性细胞、Nestin/BrdU标记阳性细胞、Tuj1/BrdU标记阳性细胞与GFAP/BrdU标记阳性细胞明显增加(P<0.05)。与脑缺血组比较，依达拉奉组缺血周围脑皮质区的Tuj1与GFAP蛋白表达量增加(P<0.05)。结论依达拉奉可促进缺血损伤侧脑室下区与缺血周围脑皮质内源性神经干细胞与星形胶质细胞的增殖，促进内源性神经干细胞分化为神经元。

Abstract

Objective To observe the effect of edaravone on endogenous neural stem cells in rats with permanent cerebral ischemia. Methods The rat model of permanent cerebral ischemia was established by electrocoagulation. Thirty SD rats were randomly divided into three groups: sham operation group, brain injury group and edaravone group. Six hours after the establishment of the model, the edaravone group was intraperitoneally injected with 1.5 g/L edaravone (10 ml/kg) once a day. The sham operation group and the cerebral ischemia group were intraperitoneally injected with saline of equal volume for 7 days. 24 hours after the last administration, BrdU positive cells, Nestin/BrdU positive cells, neuronal class Ⅲ β-tubulin（Tuj1）/BrdU positive cells and glial fibrillary acidic protein (GFAP)/BrdU positive cells were observed by immunofluorescent staining, Tuj1 and GFAP protein expressions were detected by Western blotting. Results Compared with the cerebral ischemia group, the BrdU positive cells, Nestin/BrdU positive cells, Tuj1/BrdU positive cells and GFAP/BrdU positive cells increased significantly in the infraventricular area and the cortex area around the ischemia in the edaravone group (P<0.05).Compared with the cerebral ischemia group, the expression of Tuj1 and GFAP protein in the cerebral cortex of edaravone group increased (P<0.05). Conclusion Edaravone can promote the proliferation of endogenous neural stem cells and astrocytes in the subventricular area and the cortex around ischemia, and promote the differentiation of endogenous neural stem cells into neurons.

导出引用

梁晓艳顾玉赵梦杜鑫刘宏伟周洋张铁军. 依达拉奉干预永久性脑缺血大鼠神经干细胞增殖及分化[J]. 解剖学报. 2021, 52(3): 370-376 https://doi.org/10.16098/j.issn.0529-1356.2021.03.007

LIANG Xiao-yan GU Yu ZHAO Meng DU Xin LIU Hong-wei ZHOU Yang ZHANG Tie-jun. Edaravone intervening the proliferation and differentiation of neural stem cells in rats with permanent cerebral ischemia[J]. Acta Anatomica Sinica. 2021, 52(3): 370-376 https://doi.org/10.16098/j.issn.0529-1356.2021.03.007

中图分类号： R743.3

参考文献

［1］ Zhu JB, Wang YH, Hu ZhD, et al. Research progress on pathogenesis of ischemic stroke and traditional Chinese medicine commonly used for treatment of ischemic stroke ［J］.Zhongguo Zhong Yao Za Zhi，2019，44(3):422-432. (in Chinese)

朱靖博，王永华，胡仲冬，等.缺血性脑卒中发痛机制及常用中医药治疗缺血性脑卒中的研究进展\[J\].中国中药杂志，2019,44（3）：422-432.

［2］ Wang F, Tang H, Zhu J, et al. Transplanting mesenchymal stem cells for treatment of ischemic stroke［J］.Cell Transplant，2018，27(12):1825-1834.

［3］ Enomoto M, Endo A, Yatsushige H, et al. Clinical effects of early edaravone use in acute ischemic stroke patients treated by endovascular reperfusion therapy［J］.Stroke，2019，50(3):652-658.

［4］ Li C, Mo Z, Lei J, et al. Edaravone attenuates neuronal apoptosis in hypoxic-ischemic brain damage rat model via suppression of TRAIL signaling pathway［J］.Int J Biochem Cell Biol，2018，99:169-177.

［5］ Sun Z, Xu Q, Gao G, et al.Clinical observation in edaravone treatment for acute cerebral infarction［J］. Niger J Clin Pract,2019,22(10):1324-1327.

［6］ Lee XR, Xiang GL. Effects of edaravone, the free radical scavenger, on outcomes in acute cerebral infarction patients treated with ultra-early thrombolysis of recombinant tissue plasminogen activator［J］.Clin Neurol Neurosurg,2018，167:157-161.

［7］ Xiao ZY, Wang J. Establishment of middle cerebral artery occlusion model in SD rats by electrocoagulation ［J］.Guangdong Medical Journal,2019,40(8):1074-1077.(in Chinese)

肖宗宇,汪继. 开颅电凝法建立SD大鼠大脑中动脉阻塞脑梗死模型［J］.广东医学,2019,40(8):1074-1077

［8］ Feng X, Chen ShM, Zhang WR. Effect of 13-methyltetradecanoicacid on brain edema after cerebral ischemia in rats［J］.Chinese Pharmacological Bulletin, 2019,35(1):78-84.(in Chinese)

冯晓,陈世妹,张文荣. 13-甲基十四烷酸对大鼠脑缺血后脑水肿的影响［J］.中国药理学通报, 2019,35(1):78-84.

［9］ Wang TT, Chen ZhCh, Ye X, et al.The research progress of neurogenesis in adult brain［J］.Chinese Journal of Neuroanatomy,2019,35(5):561-564.(in Chinese)

王彤彤,陈治池,叶鑫,等.成年脑神经发生机制的研究进展［J］.神经解剖学杂志, 2019,35(5):561-564.

［10］ Chen W, Chen LF, Zhang MB, et al.Effects of different melatonin treatment regimens on the proliferation of endogenous neural stem cells in neonatal rats with hypoxic-ischemic brain damage［J］.Chinese Journal of Contemporary Pediatrics,2019,21(8):830-835.(in Chinese)

陈伟,陈岚芬,张梦蓓,等.不同褪黑素治疗方案对缺氧缺血性脑损伤新生大鼠内源性神经干细胞增殖的影响［J］.中国当代儿科杂志, 2019,21(8):830-835.

［11］ Wu X, Sun NN,Lü MH, et al.Effect of different courses of electroacupuncture intervention on recognition memory and proliferation and differentiation of hippocampal neural stem cells in mice with radiation-in-duced brain injury［J］.Acupuncture Research,2019,44(11):787-792,816.(in Chinese)

武鑫,孙宁宁,吕明惠,等.不同疗程电针干预对放射线照射小鼠海马神经干细胞增殖分化的影响.［J］.针刺研究,2019,44(11):787-792,816.

［12］ Han ZH, Duan M, Li QX, et al.Influence of edaravone on cerebral edema in neonatal rats with hypoxic-ischemic encephalopathy and on CD163/HO-1 signaling pathway［J］.Chinese Journal of Comparative Medicine,2019,29(4):34-40.(in Chinese)

韩遵华,段淼,李清香，等. 依达拉奉对缺氧缺血性脑病新生大鼠脑水肿及CD163/HO-1信号通路的影响［J］.中国比较医学杂志,2019,29(4):34-40.

［13］ Xu G, Shen H, Nibona E, et al. Fundc1 is necessary for proper body axis formation during embryogenesis in zebrafish［J］. Sci Rep，2019，9(1):18910.

［14］ V ?lker J, Engert J, Ⅴ?lker C, et al. Isolation and characterization of neural stem cells from the Rat inferior colliculus［J］.Stem Cells Int，2019，2019:5831240.

［15］ Guo D, Zou J, Rensing N, et al, In vivo two-photon imaging of astrocytes in GFAP-GFP transgenic mice［J］. PLoS One，2017，12(1):e0170005.

［16］ Yuan J, Ge H, Liu W, et al. M2 microglia promotes neurogenesis and oligodendrogenesis from neural stem/progenitor cells via the PPARγ signaling pathway［J］.Oncotarget，2017，8(12):19855-19865.