摘要
目的通过探讨弥漫性轴索损伤(diffuse axonal injury,DAI)后脑组织SDF-1α及CXCR4的表达以及抑制该通路后对外周炎症细胞浸润、轴索损伤和β-APP及MMP-9表达的影响,揭示SDF-1α/CXCR4通路在DAI后炎性损伤中的作用。方法采用大鼠头颅瞬间旋转装置制备大鼠DAI模型,于造模后6、24、48、72h取脑组织,采用Western blot测定脑组织SDF-1α及其受体CXCR4的表达,并且通过给予该通路特异性抑制剂,观察外周炎症细胞浸润后相关蛋白β-APP、MMP-9的表达,及脑脊液中轴索损伤相关蛋白MBP的含量,揭示其在DAI后的炎性损伤中的作用及其机制。结果 DAI模型组皮层SDF-1α及CXCR4的表达量较对照组均显著增加,测定DAI后24h,脑皮层组织中MPO阳性细胞数、β-APP、MMP-9的表达均较对照组显著升高,脑脊液中MBP的水平也较对照组明显升高;给予CXCR4特异性抑制剂AMD3100后,脑皮层组织中MPO阳性细胞数、β-APP、MMP-9的表达较DAI模型组均明显下降,并且脑脊液中MBP水平也较DAI模型组显著下降。结论 SDF-1α/CXCR4通路活化在介导大鼠DAI后脑组织的炎性损伤中具有重要作用。
Objective By detecting the expressions of stromal cell derived factor-1α (SDF-1a) and its receptor chemokine (C-X-C motif) receptor 4 (CXCR4) in rat diffuse axonal injury (DAI) models and the effects of AMD3100 (a specific inhibitor of CXCR4) on the expressions of β-amyloid precursor protein (P-APP) and matrix metallopeptidase 9 (MMP-9), we aimed to clarify its roles in the inflammatory response and axonal injury after DAI. Methods A rat DAI model was established by using a coronal rotation device, and the brain tissue was obtained at 6 h, 24 h, 48 h and 72 h after DAI. AMD3100 was intraperitoneally injected to inhibit the SDF-la/ CXCR4 interaction. Western blot was used to detect the expressions of SDF-le, CXCR4, ^-APP and MMP-9. lmmunohistochemistry was used to observe the neutrophil infiltration and ELISA was used to detect the level of axonal injury-related protein (myelin basic protein) MBP in the cerebral spinal fluid (CSF). Results The expression of SDF-1α was significantly increased at 6 h, 24 h and 48 h after DAI compared with that in the control group, and at 24 h it reached the peak. The expression of CXCR4 was also significantly increased at 6 h, 24 h, 48 h and 72 h after DAI compared with that in the control group. /LApp and MMP-9 expressions, the number of myelopcroxidase (MPO)-positive ceils, and the MBP level in CSF at 24 h after DAI detection. After the administration of AMD3100, the expressions of β-APP and MMP-9, the number of MPO-positive cells, and the MBP level in CSF were also significantly decreased in the AMD3100 group compared with those in DAI group. Conclusion SDF-1α/CXCR4 signaling pathway plays an important role in mediating the inflammatory reaction after DAI in rats.
出处
《西安交通大学学报(医学版)》
CAS
CSCD
北大核心
2015年第1期40-44,共5页
Journal of Xi’an Jiaotong University(Medical Sciences)
基金
国家自然科学基金资助项目(No.30471774)
教育部新世纪优秀人才支持计划资助项目(No.NCET-05-0831)
陕西省自然科学基金资助项目(No.2003C1-16)~~