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缺氧诱导因子-1α、基质金属蛋白酶-9 与慢性脊髓压迫后功能恢复的相关性。

The correlation between hypoxia-inducible factor-1α, matrix metalloproteinase-9 and functional recovery following chronic spinal cord compression.

机构信息

Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, People's Republic of China.

Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, People's Republic of China.

出版信息

Brain Res. 2019 Sep 1;1718:75-82. doi: 10.1016/j.brainres.2019.04.034. Epub 2019 May 2.

Abstract

The molecular mechanisms underlying cervical spondylotic myelopathy (CSM) are poorly understood. To assess the correlation between HIF-1α, MMP-9 and functional recovery following chronic cervical spinal cord compression (CSCI). Rats in the sham group underwent C5 semi-laminectomy, while a water-absorbable polyurethane polymer was implanted into the C6 epidural space in the chronic CSCI group. Basso, Beattie and Bresnahan score and somatosensory evoked potentials were used to evaluate neurological function. Hematoxylin and eosin staining was performed to assess pathological changes in the spinal cord, while immunohistochemical analysis was used to examine HIF-1α and MMP-9 expression on days 7, 28, 42 and 70 post-surgery. Normal rats were only used for HE staining. The BBB score was significantly reduced on day 28 following CSCI, while SEPs exhibited decreased amplitude and increased latency. In chronic CSCI group, the BBB score and SEPs significantly improved on day 70 compared with day 28. HE staining revealed different level of spinal cord edema after chronic CSCI. Compared with the sham group, immunohistochemical analyses revealed that HIF-1α- and MMP-9-positive cells were increased on day 7 and peaked on day 28. HIF-1α and MMP-9 expression were demonstrated to be significantly positively correlated, whereas HIF-1α expression and BBB score were significantly negatively correlated, as well MMP-9 expression and BBB score. HIF-1α and MMP-9 expression are increased following chronic spinal cord compression and are positively correlated with one another. Decreased expression of HIF-1α and MMP-9 may contribute to functional recovery following CSCI. This expression pattern of HIF-1α and MMP-9 may give a new perspective on the molecular mechanisms of CSM.

摘要

颈椎脊髓病(CSM)的发病机制尚不清楚。本研究旨在评估慢性颈脊髓压迫(CSCI)后 HIF-1α、MMP-9 与功能恢复的相关性。假手术组大鼠行 C5 半椎板切除术,慢性 CSCI 组大鼠 C6 硬膜外腔植入可吸收性多聚体。采用 Basso、Beattie 和 Bresnahan 评分和体感诱发电位评估神经功能。采用苏木精-伊红(HE)染色评估脊髓病理变化,免疫组化分析检测术后第 7、28、42 和 70 天 HIF-1α和 MMP-9 的表达。正常大鼠仅用于 HE 染色。CSCI 后第 28 天 BBB 评分明显降低,SEP 波幅降低,潜伏期延长。慢性 CSCI 组大鼠第 70 天 BBB 评分和 SEP 较第 28 天明显改善。HE 染色显示慢性 CSCI 后脊髓水肿程度不同。与假手术组相比,免疫组化分析显示 HIF-1α 和 MMP-9 阳性细胞于第 7 天增加,第 28 天达到高峰。HIF-1α 和 MMP-9 的表达呈显著正相关,而 HIF-1α 的表达与 BBB 评分呈显著负相关,MMP-9 的表达与 BBB 评分呈显著正相关。慢性脊髓压迫后 HIF-1α 和 MMP-9 表达增加,且二者之间呈正相关。HIF-1α 和 MMP-9 表达降低可能有助于 CSCI 后的功能恢复。HIF-1α 和 MMP-9 的这种表达模式可能为 CSM 的发病机制提供新的视角。

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