Ischemic injury in the brain. Role of oxygen radical-mediated processes.
Ischemic injury in the brain. Role of oxygen radical-mediated processes.
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大脑缺血性损伤。
DOI：
10.1111/j.1749-6632.1989.tb22615.x
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发表时间：
1989
影响因子：
5.2
通讯作者：
Ginsberg,MD
中科院分区：
文献类型：
--
作者：
Watson,BD;Ginsberg,MD
自由基是在一定条件下产生的短命分子物种，被认为在生物系统中引发毒性作用。自由基在化学上是不稳定的，因此具有潜在的反应性，因为它的一个或多个价电子轨道是半满的，只有一个电子而不是通常的一对电子。自由基的反应性是由于它们倾向于通过从邻近分子中提取电子或氢原子来获得稳定的反自旋构型的热力学稳定性。也许最常见的组织自由基损伤的临床表现是电离辐射引起的。例如，放射生物学中的氧效应，即在分子氧存在的情况下，导致细胞死亡的辐射损伤增强，实质上是由逐步添加电子而导致的氧分子的还原形式介导的。这些还原形式，称为“氧自由基”或“活性氧”，包括超氧阴离子自由基（02-）及其质子化形式的过羟基自由基（HO,）产生于低pH值（单还原），过氧化氢（双重还原），和羟基自由基(OH在体内。过氧化氢是由超氧化物阴离子的分解产生的，这是一个由超氧化物歧化酶催化的反应。*羟基自由基是由过氧化氢的单电子还原得到的。当被亚铁离子催化时，这个反应被称为芬顿反应。因为铁离子是通过超氧阴离子与（铁）蛋白的相互作用从铁结合位点释放出来的？该反应是“特定地点”的，被指定为铁催化的、超氧化物驱动的芬顿反应。（没有铁离子的氧化还原参与，这个过程被称为Haber-Weiss反应。）过羟基自由基，“尤其是羟基自由基”，可以从不饱和脂肪酸中强力地提取氢原子，形成脂质自由基；这是脂质过氧化链过程的第一步。脂质过氧化也被称为脂质自氧化，因为在氧存在下脂质自由基会自发过氧化（直接添加分子氧）。生成的过氧自由基能够从邻近分子中提取一个氢原子，从而将自由基的性质转移到目标分子中，同时将自身转化为中性的过氧化氢摩尔规则。，~* ' ~* ' ~新的自由基可以重新启动并以链式方式传播循环。产物氢过氧化物可以用类似于芬顿反应的方式被亚铁离子解离成烷氧基自由基。
Free radicals are short-lived molecular species, produced under certain conditions, that are believed to initiate toxic effects in biological systems.’-3 A free radical is chemically unstable, and thus potentially reactive, because one or more of its valence electron orbitals is half-filled, with just one electron instead of the usual pair of electrons. The reactivity of free radicals results from their propensity to acquire thermodynamic stability in the stable, opposite-spin configuration by abstracting electrons or hydrogen atoms from adjacent molecules. Perhaps the most familiar clinical expression of free radical injury in tissues is that induced by ionizing radiation. For example, the oxygen effect4 of radiobiology, in which radiation damage leading to cell death is enhanced in the presence of molecular oxygen, is substantially mediated by reduced forms of the oxygen molecule resulting from the stepwise addition of electrons. These reduced forms, called “oxygen radicals” or “active oxygens,” include the superoxide anion radical (02-) and its protonated form the perhydroxyl radical (HO,.) produced at low pH (both singly reduced), hydrogen peroxide (doubly reduced), and hydroxyl radical (OH In vivo. hydrogen peroxide is produced by dismutation of superoxide anions, a reaction catalyzed by the enzyme superoxide dismutase.* Hydroxyl radical is derived by single electron reduction of hydrogen peroxide. When catalyzed by ferrous ion, this reaction is known as the Fenton reaction. Because ferrous ion is released from iron-binding sites by the interaction of superoxide anion with (ferri) proteins? the reaction is “site specific,” and is designated as the iron-catalyzed, superoxide-driven Fenton reaction.”(Without the redox participation of iron ions, the process is known as the Haber-Weiss reaction.) The perhydroxyl radical,” and especially the hydroxyl radical,’, can vigorously abstract hydrogen atoms from unsaturated fatty acids to form lipid radicals; this is the initial step in the chain process of lipid peroxidation. Lipid peroxidation is also known as lipid autoxidation, because in the presence of oxygen the lipid radical is spontaneously peroxidized (molecular oxygen is added directly). The resultant peroxy radical is capable of abstracting a hydrogen atom from a neighboring molecule, thus transferring radical character to this target molecule while transforming itself into a neutral hydroperoxide mole~ ule.”,~*’~*’~ The new radical can then reinitiate and propagate the cycle in chain fashion. The product hydroperoxides can be dissociated by ferrous ion into alkoxyl free radicals, in a manner analogous to the Fenton reaction.