Trehalose treatment suppresses inflammation, oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage.
Trehalose treatment suppresses inflammation, oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage.
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DOI：
10.1186/1479-5876-10-80
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发表时间：
2012-04-30
影响因子：
7.4
通讯作者：
Sasaki N
中科院分区：
文献类型：
--
作者：
Echigo R;Shimohata N;Karatsu K;Yano F;Kayasuga-Kariya Y;Fujisawa A;Ohto T;Kita Y;Nakamura M;Suzuki S;Mochizuki M;Shimizu T;Chung UI;Sasaki N
蛛网膜下腔出血（SAH）经常导致一些并发症，包括脑血管痉挛，与高死亡率相关。虽然脑血管痉挛是SAH后脑损伤的主要原因，但其他因素如炎症反应和氧化应激也导致SAH后的高死亡率。海藻糖是一种非还原性双糖，其中两个葡萄糖单元通过α，α-1,1-糖苷键连接，已被证明在许多生物体中诱导对各种应激源的耐受性。本研究在体外和体内研究海藻糖对血液诱导的脑血管痉挛、炎症反应和氧化应激的影响。用溶血液处理巨噬细胞样细胞，采用酶免疫法检测类20蛋白、促炎细胞因子和内皮素-1的表达，并用western blotting分析环氧化酶-2、诱导型一氧化氮合酶和NF-κB抑制剂的表达。用溶血液和过氧化氢处理后，还分析了过氧化脂质水平和花生四烯酸释放量。在实验性SAH发作3小时后，18只日本大白兔在大池中注射生理盐水、海藻糖或麦芽糖。对基底动脉进行了血管造影和组织学分析。在另一项研究中，将60只大鼠的股动脉暴露于新鲜的自体血液中。在治疗后1、3、5、7、10和20天，对从股动脉制备的冷冻切片进行组织学分析。当用溶血液处理细胞时，海藻糖抑制几种炎症介质的产生和NF-κB抑制剂的降解，并抑制脂质过氧化、活性氧诱导的花生四烯酸的体外释放。在家兔模型中，海藻糖对实验性SAH发作后的血管痉挛有抑制作用，而麦芽糖只有中等作用。对暴露于血液中的大鼠股动脉进行了20天的观察，组织学分析显示海藻糖抑制血管痉挛、炎症反应和脂质过氧化。这些数据表明海藻糖对SAH后的一些病理事件有抑制作用，包括血管痉挛、炎症反应和脂质过氧化。海藻糖可能是一种新的治疗SAH并发症的方法。
Subarachnoid hemorrhage (SAH) frequently results in several complications, including cerebral vasospasm, associated with high mortality. Although cerebral vasospasm is a major cause of brain damages after SAH, other factors such as inflammatory responses and oxidative stress also contribute to high mortality after SAH. Trehalose is a non-reducing disaccharide in which two glucose units are linked by α,α-1,1-glycosidic bond, and has been shown to induce tolerance to a variety of stressors in numerous organisms. In the present study, we investigated the effect of trehalose on cerebral vasospasm, inflammatory responses, and oxidative stress induced by blood in vitro and in vivo. Enzyme immunoassay for eicosanoids, pro-inflammatory cytokines, and endothelin-1, and western blotting analysis for cyclooxygenase-2, inducible nitric oxide synthase, and inhibitor of NF-κB were examined in macrophage-like cells treated with hemolysate. After treatment with hemolysate and hydrogen peroxide, the levels of lipid peroxide and amounts of arachidonic acid release were also analyzed. Three hours after the onset of experimental SAH, 18 Japanese White rabbits received an injection of saline, trehalose, or maltose into the cisterna magna. Angiographic and histological analyses of the basilar arteries were performed. In a separate study, the femoral arteries from 60 rats were exposed to fresh autologous blood. At 1, 3, 5, 7, 10, and 20 days after treatment, cryosections prepared from the femoral arteries were histologically analyzed. When cells were treated with hemolysate, trehalose inhibited the production of several inflammatory mediators and degradation of the inhibitor of NF-κB and also suppressed the lipid peroxidation, the reactive oxygen species-induced arachidonic acid release in vitro. In the rabbit model, trehalose produced an inhibitory effect on vasospasm after the onset of experimental SAH, while maltose had only a moderate effect. When the rat femoral arteries exposed to blood were investigated for 20 days, histological analysis revealed that trehalose suppressed vasospasm, inflammatory response, and lipid peroxidation. These data suggest that trehalose has suppressive effects on several pathological events after SAH, including vasospasm, inflammatory responses, and lipid peroxidation. Trehalose may be a new therapeutic approach for treatment of complications after SAH.
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影响因子：
3.3
作者：
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通讯作者：
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通讯作者：
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影响因子：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Squadrito, Francesco