原位气泡在减压病脊髓神经元损伤中的作用及机制研究

Decompression sickness spinal cord injury (DCS-SCI), the core medical problems in diving operations, is a serious disease with complicated symptoms and severe consequences. As the the underlying pathogenesis is poorly understood, there is still short of effective prevention and treatment measures. Bubble formation during decompression process is the fundamental cause of DCS-SCI and glial cell activation is an important damage factor. However, until now, the direct effects of autochthonous bubbles on spinal cord neuron injury, the glial cells activation mechanism and their role in bubble-induced spinal cord neuron injury have not been explored. Studies have shown that bubble contact can induce vascular endothelial cell damage and even death by increasing influx of extracellular Ca2+. Our preliminary experimental results showed that, in addition to activating the glial cells, bubble contact can also significantly increase intracellular Ca2+ levels and induce apoptosis in spinal cord neurons. Based on these results, in this study, primary cultured cells and DCS-SCI rats model were employed to further investigate the effects of bubble contact on glial cell activation and role of extracellular Ca2+ influx and activated glial cells in bubble-contact induced spinal cord neuron injury. This study may clarify the effects of autochthonous bubbles on DCS spinal cord neurons injury and provide theoretical basis for the further exploration of the pathogenesis of DCS-SCI and the development of prevention and treatment measures.

减压病脊髓损伤（DCS-SCI）是潜水作业中的核心医学问题，起病急、病情重、救治困难。由于发病机制尚未完全明确，仍缺乏有效的防治措施。减压过程中气泡的形成是DCS-SCI的根本原因，胶质细胞活化则是重要损伤因素。但是，在DCS-SCI发病过程中原位气泡对脊髓神经元的直接损伤作用、胶质细胞活化途径及其活化后在气泡损伤神经元中的作用尚不明确。研究表明气泡触碰能通过增加胞外Ca2+内流诱导血管内皮细胞损伤甚至死亡。我们的研究发现，气泡触碰除能激活胶质细胞外，也能显著增加脊髓神经元胞内Ca2+水平以及诱导其凋亡。本项目拟在动物和细胞水平，通过进一步观察胞外Ca2+内流在气泡损伤脊髓神经元中的作用、气泡对胶质细胞活化的影响及其活化后在气泡损伤脊髓神经元中的作用，初步阐明原位气泡在减压病脊髓神经元损伤中的作用及机制，为DCS-SCI发病机制和防治措施的进一步探索提供借鉴。

背景：减压病脊髓损伤（DCS-SCI）是潜水作业中的核心医学问题，起病急、病情重、救治困难。由于发病机制尚未完全明确，仍缺乏有效的防治措施。减压过程中气泡的形成是DCS-SCI的根本原因，胶质细胞活化则是重要损伤因素。但是，在DCS-SCI发病过程中气泡对脊髓神经元的直接损伤作用、胶质细胞活化在气泡损伤神经元中的作用均尚待进一步观察。.内容：（1）气泡触碰对脊髓神经元的直接损伤作用及规律：气泡触碰可直接导致脊髓神经元损伤，在一定范围内，气泡直径越大，触碰时间越长，损伤越明显。（2）气泡触碰对脊髓星形胶质细胞和小胶质细胞活化的影响：气泡触碰均可直接激活星形胶质细胞和小胶质细胞。不同直径气泡对星形胶质细胞和小胶质细胞的激活作用无显著差异。气泡触碰激活小胶质细胞后可促进星形胶质细胞活化，但是星形胶质细胞激活后对小胶质细胞的活化无明显影响。（3）星形胶质细胞和小胶质细胞活化在气泡触碰损伤脊髓神经元中的作用：星形胶质细胞和小胶质细胞激活后可加重气泡触碰所致脊髓神经元损伤。（4）芦丁对SD大鼠减压病脊髓损伤的保护效应：提前给与芦丁可以有效降低大鼠DCS发病率，减轻脊髓炎症和氧化损伤。.结论：减压所致脊髓组织内形成的原位气泡一方面可以直接损伤脊髓神经元，另一方面也可以通过激活胶质细胞，释放炎症因子等加重脊髓神经元损伤。