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首页> 美国卫生研究院文献>other >Gamma-Tocopherol Nebulization Decreases Oxidative Stress Arginase Activity and Collagen Deposition after Burn and Smoke Inhalation in the Ovine Model
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Gamma-Tocopherol Nebulization Decreases Oxidative Stress Arginase Activity and Collagen Deposition after Burn and Smoke Inhalation in the Ovine Model

机译：γ-生育酚雾化降低氧化胁迫氨基酶活性和在绵羊模型中燃烧和吸入后的胶原沉积

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More than 20,000 burn injury victims suffer from smoke inhalation injury in the United States annually. In an ovine model of acute lung injury, gamma-tocopherol (g-T) had a beneficial effect when nebulized into the airway. We hypothesize that g-T scavenges reactive oxygen and nitrogen species (ROS/RNS) resulting from burn and smoke inhalation injury and that these ROS/RNS activate the arginase pathway, leading to increased collagen deposition and decreased pulmonary function. To test this hypothesis, ewes were operatively prepared for chronic study, then they were randomly divided into groups (n=8): uninjured, injured, or injured with nebulization (g-T (950 mg/g) and alpha-T (40 mg/g) from hours 3–48 after the injury. The injury, under deep anesthesia, consisted of a 20% total body surface burn and 36 breaths of cotton smoke; all animals were euthanized after 3 weeks. Treatment increased lung g-T at three weeks post-g-T nebulization compared to injured sheep (1.75 ± 0.62 nmol/g vs 0.45 ± 0.06, p<0.05). The expression of dimethylarginine dimethylaminohydrolase-2, which degrades asymmetrical dimethylarginine, a nitric oxide synthase inhibitor, significantly increases with g-T treatment compared to injured sheep (p<0.05). Arginase activity (0.15 ± 0.02 µM urea/µg protein vs 0.24 ± 0.009, p<0.05), ornithine aminotransferase (11,720 ± 888 vs 13,170 ± 1775), and collagen deposition (0.62 ± 0.12 µM hydroxyproline/µg protein vs 1.02 ± 0.13, p<0.05) significantly decrease with g-T compared to injured animals without g-T. The decreases in arginase and collagen with g-T are associated with significantly increased diffusion capacity (p<0.05) and decreased lung wet-to-dry ratio (p<0.05). Smoke-induced chronic pulmonary dysfunction is mediated through the ROS/asymmetrical dimethylarginine/arginase pathway and ROS scavengers such as g-T may be a potential therapeutic management of burn patients with inhalation injury.
机译：在美国，每年有超过20,000名烧伤伤害受害者遭受烟雾吸入伤害。在急性肺损伤的绵羊模型中，将γ-生育酚（g-T）雾化入气道具有有益的作用。我们假设g-T清除了烧伤和烟雾吸入损伤引起的活性氧和氮物质（ROS / RNS），并且这些ROS / RNS激活了精氨酸酶途径，导致胶原蛋白沉积增加和肺功能下降。为了验证这一假设，可操作地将母羊准备进行慢性研究，然后将其随机分为几组（n = 8）：未受伤，受伤或雾化受伤（gT（950 mg / g）和alpha-T（40 mg / g）从受伤后3–48小时开始，深麻醉下的受伤包括20％的全身表面烧伤和36次棉烟呼吸；所有动物在3周后被安乐死，治疗后3周肺gT增加-gT雾化与受伤绵羊相比（1.75±0.62 nmol / g vs 0.45±0.06，p <0.05）。降解一氧化氮合酶抑制剂不对称二甲基精氨酸的二甲基精氨酸二甲基氨基水解酶-2的表达与gT处理相比显着增加受伤的绵羊（p <0.05）。精氨酸酶活性（0.15±0.02 µM尿素/ µg蛋白vs 0.24±0.009，p <0.05），鸟氨酸氨基转移酶（11,720±888 vs 13,170±1775）和胶原蛋白沉积（0.62±0.12 µM羟脯氨酸/ µg蛋白vs 1.02±0.13，p <0.05）显着降低与没有g-T的受伤动物相比，有g-T的动物会增加。带有g-T的精氨酸酶和胶原蛋白的减少与扩散能力显着增加（p <0.05）和肺湿干比降低（p <0.05）有关。烟雾引起的慢性肺功能障碍是通过ROS /不对称二甲基精氨酸/精氨酸酶途径介导的，ROS清除剂（如g-T）可能是烧伤吸入性损伤患者的潜在治疗方法。

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