Critical role of acrolein in secondary injury following ex vivo spinal cord trauma.
Critical role of acrolein in secondary injury following ex vivo spinal cord trauma.
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DOI：
10.1111/j.1471-4159.2008.05622.x
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发表时间：
2008-11
影响因子：
4.7
通讯作者：
Shi R
中科院分区：
文献类型：
--
作者：
Hamann K;Durkes A;Ouyang H;Uchida K;Pond A;Shi R
脊髓损伤（SCI）的病理生理学特征是最初的原发性损伤，随后是继发性损伤过程，其中氧化应激是关键组成部分。继发性损伤过程不仅会加剧原发性损伤部位的病理，还会导致损伤扩散到邻近的健康组织。脂质过氧化副产物丙烯醛被认为是继发性损伤的一种潜在介质。为了进一步严格阐明丙烯醛在继发性损伤中的作用，利用独特的离体模型来分离机械损伤与SCI后内源性产生的毒素（例如丙烯醛）的有害影响。我们证明：1）丙烯醛-赖氨酸加合物能够从受压组织扩散到邻近的未受伤组织； 2）继发性损伤本身会产生显着的膜损伤并增加超氧化物的产生； 3) 丙烯醛清除剂肼屈嗪可显着减轻这些损伤。此外，肼苯哒嗪治疗可在压缩损伤后 2 小时内显着减少膜损伤，但不是在压缩损伤后立即出现。这些发现支持我们的假设，即 SCI 后，丙烯醛增加至病理浓度，对继发性损伤有显着贡献，因此代表了促进恢复的新清除目标。
The pathophysiology of spinal cord injury (SCI) is characterized by the initial, primary injury followed by secondary injury processes in which oxidative stress is a critical component. Secondary injury processes not only exacerbate pathology at the site of primary injury, but also result in spreading of injuries to the adjacent, otherwise healthy tissue. The lipid peroxidation byproduct acrolein has been implicated as one potential mediator of secondary injury. In order to further and rigorously elucidate the role of acrolein in secondary injury, a unique ex vivo model is utilized to isolate the detrimental effects of mechanical injury from toxins such as acrolein that are produced endogenously following SCI. We demonstrate that: 1) acrolein-lys adducts are capable of diffusing from compressed tissue to adjacent, otherwise uninjured tissue; 2) secondary injury by itself produces significant membrane damage and increased superoxide production; and 3) these injuries are significantly attenuated by the acrolein scavenger hydralazine. Furthermore, hydralazine treatment results in significantly less membrane damage 2 hours following compression injury, but not immediately after. These findings support our hypothesis that, following SCI, acrolein is increased to pathologic concentrations, contributes significantly to secondary injury, and thus represents a novel target for scavenging to promote improved recovery.
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影响因子：
3.6
作者：
Burcham, PC;Fontaine, FR;Pyke, SM
通讯作者：
Pyke, SM
DOI：
10.1124/jpet.104.067330
发表时间：
2004-09-01
影响因子：
3.5
作者：
Kaminskas, LM;Pyke, SM;Burcham, PC
通讯作者：
Burcham, PC
DOI：
10.1080/15287390490276539
发表时间：
2004-03-26
影响因子：
2.6
作者：
Li, H;Wang, JL;Khan, MF
通讯作者：
Khan, MF
影响因子：
4.4
作者：
Peasley, MA;Shi, RY
通讯作者：
Shi, RY
影响因子：
4.7
作者：
Luo, J;Borgens, R;Shi, R
通讯作者：
Shi, R