自由基與敗血症：超氧歧化酶的角色

Free Radicals and Sepsis: Role of Superoxide Dismutase

廖文進(Wen-Jinn Liaw) ； 吳錦楨(Chin-Chen Wu) ； 何善台(Shung-Tai Ho) ； 王志中(Jhi-Joung Wang)

《重症醫學雜誌》 9卷1期 (2008/03) Pp. 10-19

https://doi.org/10.30035/TCCM.200803.0002

摘要

不論人體或動物，一旦罹患敗血性休克，將會出現血流量異常分佈、白血球與血小板聚集、血管內皮受損與凝血異常等現象。敗血性休克時，白血球會釋放活性氧類(reactive oxygen species, ROS)，包括超氧游離基(superoxide anion, O2(上標 •-))與過氧化氫(hydrogen peroxide, H2O2)等，會傷害細胞、組織與DNA，造成細胞膜磷酯質過氧化，會改變胞膜流體特性，喪失細胞完整性，導致能量降低及器官衰竭，甚至死亡。事實上，在正常生理過程中生物體即會產生小量的O2(上標 •-)，靠著體內的清道夫（抗氧化物），例如超氧化歧化酶(superoxide dismutase, SOD)、維他命E、維他命C及穀胱甘太過氧化酶(glutathione peroxidase, GPx)等將之中和，所以不會造成急性傷害。但是，在敗血性休克時，大量的O2(上標 •-)被釋放出來，超過生物體正常的清除能力範圍，就會導致傷害之結果
因爲，各種疾病狀態，O2(上標 •-)造成組織損傷及其伴隨之發炎反應都是以相似的方式進行。這樣的共同徑路提供了一個容易操控或治療的機會，因爲只要給予能夠清除O2(上標 •-)的藥物便可達到目的。因此，抗氧化劑SOD擬似物(SOD mimetics)就被認爲是非常具有前瞻性的治療藥物。研究發現，兒茶酚胺(catecholamines)本身被O2(上標 •-)攻擊後，會失去其效用。給予新腎上腺素(norepinephrine)會有低反應性現象是因爲被O2(上標 •-)攻擊而去失活性。此現象可以被SOD擬似物保護而不被氧化。
儘管生物體平時就會不斷產生自由基，本身也有很有效率的防衛機轉，但是，在某種壓力下，例如敗血症或敗血性休克時，O2(上標 •-)產量激增，而負責維持平衡的SOD活性反而下降。此時，提供SOD擬似物，例如Tempol，不但可以幫忙協助移除多餘的O2(上標 •-)，也可進一步降低趨炎細胞素的釋放，減少其進一步的傷害。

關鍵字

活性氧類 ； 超氧游離基 ； 敗血症 ； 超氧化歧化酶

並列摘要

Both in patients and animals with septic shock, maldistribution of blood flow, damage to endothelium, coagulation abnormalities, and aggregation of platelets and neutrophils are observed. The activation of neutrophils causes the release reactive oxygen species (ROS) including superoxide anion (O2(superscript •-)) and hydrogen peroxide (H2O2), which can damage cells, tissue, and DNA, and peroxidation of membrane phospholipids, which can alter membrane fluidity and lead to loss of cellular integrity, and low energy, organ failure and even death. In fact, O2(superscript •-) can be release in normal physiologic condition, which can be scavenged by antioxidant (superoxide dismutase, SOD), vitamin E, vitamin C, and glutathione peroxidase (GPx) to avoid acute injury. However, when animal or human in septic shock large amount of O2(superscript •-) is released, which is over the scavenging ability, and causes injury.
Because various disease states, as O2(superscript •-) produce tissue injury and associated inflammation in all tissues are in similar ways. This commonality provides a unique opportunity to manipulate with an agent that removes O2(superscript •-) to prevent or treat the diseased state. So, SOD mimetics are considered as an useful agent to manage sepsis. It has been found that catecholamines can be deactivation by O2(superscript •-). Hyporeactivity will develop in norepinephrine administration due to its deactivation by O2(superscript •-). Nevertheless, this can be protected by treatment of SOD.
Although free radical is produced in normal condition and there is an effective antioxidant mechanism, release of O2(superscript •-) increased extremely, but the activity of SOD suppressed during stress, e.g. sepsis or septic shock. So, SOD mimetics, e.g. Tempol, not only provide removal of O2(superscript •-), but also reduce proinflammatory cytokines to prevent damage.

並列關鍵字

Release reactive oxygen species ； Superoxide anion ； Sepsis ； Superoxide dismutase