新生小鼠缺氧缺血脑组织基质细胞衍生因子1α的表达及其作用

doi:10.6040/j.issn.1671-7554.0.2015.097

摘要/Abstract

摘要： 目的观察基质细胞衍生因子1α(SDF-1α)在新生小鼠缺氧缺血性脑组织中的表达模式,及外源性给予SDF-1α对新生小鼠脑组织增殖细胞相关核抗原ki67表达和小鼠神经行为学的影响。方法将90只KM小乳鼠分为空白组、缺氧缺血性脑损伤模型组(HIBD模型组)和SDF-1α组,每组30只。HIBD模型组和SDF-1α组于HIBD造模后30 min分别腹腔注射0.9% NaCl和SDF-1α(每只小鼠2.0 μg/d),3个亚组分别连续腹腔注射1、3、7 d,空白组仅腹腔注射等体积0.9% NaCl。通过免疫荧光与Real-time PCR观察HIBD后不同时间点SDF-1α的表达情况,通过免疫荧光及Western blotting观察ki67的表达,通过高架十字迷宫实验观察小鼠神经行为学的变化。结果 HIBD模型组脑组织SDF-1α表达上调,第3天达高峰,与空白组相比,差异有统计学意义(P<0.01)。SDF-1α组ki67在各时间点的表达均较HIBD模型组增加(P≤0.01),小鼠的神经行为学表现也较HIBD模型组明显改善(P<0.05)。结论 SDF-1α在脑组织缺氧缺血损伤后表达上调且有时间窗。外源性SDF-1α可促进ki67的表达,对发生缺氧缺血性脑损伤的小鼠的神经行为学表现有改善作用。

关键词: 基质细胞衍生因子1α, 脑损伤, 脑缺氧缺血, ki67, 神经行为学

Abstract: Objective To explore the expression of stromal cell derived factor-1α(SDF-1α) in the brain of mice after hypoxic ischemic brain damage (HIBD), and to discuss the effects of SDF-1α on the expression of ki67 and the improvement of neurological behavior. Methods Ninety KM newborn mice were devided into blank control group, HIBD model group and SDF-1α group, with 30 mice in each group. HIBD model group and SDF-1α group were intraperitoneal injected with 0.9% NaCl and SDF-1α(2.0 μg/d in each group) respectively at 30 min after HIBD modeling. Three subgroups were intraperitoneal injected with SDF-1α for 1, 3, 7 d, while blank control group were injected with equivalent 0.9% NaCl. SDF-1α expression at different time points were observed by immunofluorescence and Real-time PCR. ki67 expression was observed by immunofluorescence and Western blotting. Neurobehavioral improvement were recorded by elevated plus maze. Results SDF-1α expression in HIBD model group increased and reached a peak on the third day, and the difference between this group and blank control group was statistically significant (P<0.01). ki67 expression significantly increased in SDF-1α group, compared with that in HIBD model group (P≤0.01). Theneurological behavior of mice in SDF-1α group also was improved, compared with HIBD model group(P<0.05). Conclusion SDF-1α expression is upregulated in HIBD model group, and reaches a peak on the third day. Exogenous SDF-1α induces the expression of ki67, and improves the learning ability of mice with HIBD.

Key words: Brain hypoxic-ischemic, ki67, Neurobehavioral, Brain injuries, Stromal cell derived factor-1α

中图分类号:

R725

李媛媛, 张楠, 徐谧, 秦明明, 窦冬冬, 朱薇薇. 新生小鼠缺氧缺血脑组织基质细胞衍生因子1α的表达及其作用[J]. 山东大学学报（医学版）, 2015, 53(10): 26-31.

LI Yuanyuan, ZHANG Nan, XU Mi, QIN Mingming, DOU Dongdong, ZHU Weiwei. Expression of stromal cell derived factor-1α and its effects in hypoxic-ischemic brain tissue of neonatal mice[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(10): 26-31.

参考文献

[1] Takenouchi T, Sugiura Y, Morikawa T, et al. Therapeutic hypothermia achieves neuroprotection via a decrease in acetylcholine with a concurrent increase in carnitine in the neonatal hypoxia-ischemia[J]. J Cereb Blood Flow Metab, 2015, 35(5):794-805.
[2] Shroff G, Gupta A, Barthakur J. Therapeutic potential of human embryonic stem cell transplantation in patients with cerebral palsy[J]. J Transl Med, 2014, 12(1):318. doi: 10.1186/s12967-014-0318-7.
[3] Heo JS, Choi SM, Kim HO, et al. Neural transdifferentiation of human bone marrow mesenchymal stem cells on hydrophobic polymer-modified surface and therapeutic effects in an animal model of ischemic stroke[J]. Neuroscience, 2013, 238:305-318.
[4] Subramanian P, Karshovska E, Reinhard P, et al. Lysophosphatidic acid receptors LPal and LPA3 promote CXCL12-mediated smooth muscle progenitor cell recruitment in neointima formation[J]. Circ Res, 2010, 107(1):96-105.
[5] 任素伟,崔志慧,黄托夫,等. p-p38 MAPK在A2AR敲除新生小鼠缺氧缺血脑区的表达及意义[J]. 中国病理生理杂志, 2013,29(1):36-42. REN Suwei, CUI Zhihui, HUANG Tuofu, et al. Expression of p-p38 MAPK in partial cerebral tissues after hypoxic-ischemic brain damage in neonatal A2AR knockout mice[J]. Chinese Journal of Pathophysiology, 2013, 29(1):36-42.
[6] Yu J, Li M, Qu Z, et al. SDF-1/CXCR4-mediated migration of transplanted bone marrow stromal cells toward areas of heart myocardial infarction through activation of PI3K/Akt[J]. J Cardiovasc Pharmacol, 2010, 55(5):496-505.
[7] Liu X, Zhou C, Li Y, et al. SDF-1 promotes endochondral bone repair during fracture healing at the traumatic brain injury condition[J]. PLoS One, 2013,8(1):e54077. doi: 10.1371/journal.pone.0054077.
[8] Wang K, Zhao X, Kuang C, et al. Overexpression of SDF-1α enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via CXCR4/PI3K pathway[J]. PLoS One, 2012, 7(9):e43922. doi: 10.1371/journal.pone.0043922.
[9] Wang Y, Huang J, Li Y, et al. Roles of chemokine CXCL12 and its receptors in ischemic stroke[J].Curr Drug Targets, 2012, 13(2):166-172.
[10] Li S, Wei M, Zhou Z, et al. SDF-1α induces angiogenesis after traumatic brain injury[J]. Brain Res, 2012, 20(3):76-86.
[11] Ryu CH, Park SA, Kim SM, et al. Migration of human umbilical cord blood mesenchymal stem cells mediated by stromal cell-derived factor-1/CXCR4 axis via Akt, ERK, and p38 signal transduction pathways[J]. Biochem Biophys Res Commun, 2010, 398(1):105-110.
[12] Li M, Yu J, Li Y, et al. CXCR4 positive bone mesenchymal stem cells migrate to human endothelial cell stimulated by ox-LDL via SDF-1alpha/CXCR4 signaling axis[J]. Exp Mol Pathol, 2010, 88(2):250-255.
[13] 刘小河,周平,孙大定,等. 温胆片对高架十字迷宫实验小鼠的抗焦虑作用[J]. 中药新药与临床药理, 2012, 23(5):519-521. LIU Xiaohe, ZHOU Ping, SUN Dading, et al. Anti-anxiety effect of Wendan tablets on mice in elevated plus maze test[J]. Traditional Chinese Drug Research and Clinical Pharmacology, 2012, 23(5):519-521.
[14] Godlevsky LS, Muratova TN, Kresyun NV, et al. Anxiolytic and antidepressive effects of electric stimulation of the paleocerebellar cortex in pentylenetetrazol kindled rats[J]. Acta Neurobiol Exp (Wars), 2014, 74(4):456-464.
[15] Liu Y, Namba T, Liu J, et al. Glial fibrillary acidic protein-expressing neural progenitors give rise to immature neurons via early intermediate progenitors expressing both glial fibrillary acidic protein and neuronal markers in the adult hippocampus[J]. Neuroscience, 2010, 166(1):241-251.
[16] Namba T, Mochizuki H, Suzuki R, et al. Time-lapse imaging reveals symmetric neurogenic cell division of GFAP-expressing progenitors for expansion of postnatal dentate granule neurons[J]. PLoS One, 2011, 6(9):e25303. doi: 10.1371/journal.pone.0025303.
[17] do Carmo A, Patricio I, Cruz MT, et al. CXCL12/CXCR4 promotes motility and proliferation of glioma cells[J]. Cancer Biol Ther, 2010, 9(1):56-65.

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