| 摘要: |
| 目的：观察减压性中枢神经系统损伤及高压氧（HBO）处理后小胶质细胞活性的变化，探讨小胶质细胞在减压性中枢神经损伤中的作用及其可能的机制与HBO效用的机制。方法：动物分为正常对照组、安全减压对照组、致伤组、HBO治疗组。以不安全快速减压大鼠中枢神经损伤模型为实验对象，致伤后6h给予HBO处理。观察活化小胶质细胞、TNF—α／TACE免疫阳性细胞、神经细胞凋亡，组织内TNF—α含量和脑脊液（CSF）内TNF—α的生物活性。结果：损伤后6h就可见脑和脊髓组织内IB4阳性活化小胶质细胞，数量的高峰出现在24h，活化的小胶质细胞出现形态改变。神经元凋亡在损伤后48h达到高峰。小胶质细胞出现的区域与神经细胞凋亡出现的区域相同。损伤后6h就可在CNS组织中检测到TNF-α，48h达到高峰，与IB4阳性细胞及神经细胞凋亡指数呈正相关（P〈0．05）。CSF中TNF—α的生物活性也出现相同的变化趋势。TNF—α和TACE免疫阳性细胞形态和分布与IB4阳性细胞类似。HBO治疗可显著减少中枢神经组织中活化小胶质细胞的数量，降低组织和CSF中TNF—α的含量，减少神经细胞凋亡。结论：减压性损伤中枢神经组织内小胶质细胞迅速激活，后者增加毒性物质的表达和分泌，介导继发损伤。HBO能够抑制小胶质细胞反应，降低其活性，减少毒性物质的分泌，起到神经元保护作用 |
| 关键词: 气压性损伤 中枢神经系统 小胶质细胞 高压氧 神经元 肿瘤坏死因子α |
| DOI：10.3724/SP.J.1008.2007.00127 |
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| 基金项目:海军后勤科研基金（03-3303）. |
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| Dysbaric injury of rats＇ central nervous system： the role of microglia |
| CHEN Rui-yong , LIU Jing-chang , FANG Yi-qun , YIN Ming, ZHAO Min , ZHANG Jun , YAO Jian , JIANG Ping , ZHANG Min , CHEN Hai-ting , LIN Shi-long |
| (1. Navy Medical Research Institute, Shanghai 200433, China; 2. Graduate Student Department, Second Military Medical University, Shanghai 200433; 3. Central Laboratory, Changhai Hospital, Second Military Medical University; 4. Medical Education Division, Changhai Hospital, Second Military Medical University) |
| Abstract: |
| Objective：To observe the change of microglia activity after fast decompressing and/or hyperbaric oxygenation （HBO）-induced central nervous system （CNS） damage, so as to study the role of microglia in CNS dysbaric injury and the effects of HBO on microglia. Methods.. Rats were randomly divided into the following groups., normal control, safe decompressing, fast decompressing （FD） injured, and HBO treated groups. Rat models of dysbaric injury were established by FD; 6 h later the rat models were subjected to HBO treatment. The activated microglia were detected by FITC-linked Isolectin B4; TNF-α and TNF-α converting enzyme （TACE） positive cells were detected immunohistochemically; and neural apoptosis was detected by TUNEL assay. TNF-α contents in CNS tissue were determined by ELISA and the bioactivity of sTNF-α in cerebrospinal fluid （CSF） were determined by L929 cell cytotoxicity bioassay. Results： IB4 positive microglia appeared in rats＇ CNS 6 h after FD treatment, peaked after 24 h, and declined thereafter. The activated microglia had morphological changes. Cell apoptosis indices of CNS reached its peak 48 h after FD treatment. Activated microglia and apoptotic neurons had similar distribution. TNF-α was detected in the brain and spinal cord 6 h after FD, significantly increased after 24 h, and peaked after 48 h. The content of TNF-α was positively correlated with IB4 positive cells and apoptosis index （P〈0.05）. TNF-α bioactivity in CSF of FD group had a similar change to TNF-α content in CNS tissue. The IHC results showed that, TNF-α and TACE positive cells had the same morphology and distribution to those of IB4 positive cells. HBO treatment significantly decreased IB4 positive cells after 24 h, 48 h, and 72 h, reduced TNF-α content in CNS tissues and TNF-α cytotoxicity in CSF; and decreased the apoptosis index after 48 h and 72 h. Conchlusion： Microglial cells are quickly activated after dysbaric-induced injury of CNS. The activated microglia play a role in secondary injury through increasing TNF-α and TACE expression. HBO therapy can protect the neurons through depressing the activation and proliferation of microglia and reducing secretion of neurotoxin. |
| Key words: dysbaric injury central nerve system microglial cell hyperbaric oxygen neuron tumor necrosis factor-α |
