重组人硫氧还蛋白可降低间歇性低氧小鼠胸主动脉外膜低氧诱导因子1和肿瘤坏死因子α的表达

Recombinant human thioredoxin decreased the expression level of thioredoxin, hypoxia-inducible factor-1 and tumor necrosis factor-ct in adventitia of thoracic aorta in mice model

目的以慢性间歇性低氧小鼠作为动物模型，观察重组人硫氧还蛋白（recombinant human thioredoxin，hTRX）对小鼠胸主动脉低氧诱导因子1（HIF-1）和肿瘤坏死因子1（TNF-1）表达的影响，以探讨hTRX对慢性间歇性低氧引起的炎症反应和氧化应激的作用。方法自制低氧舱进行长期间歇性低氧试验。以成年昆明小鼠为研究对象，随分为三组：对照组（8只），间歇性低氧组（8只）及hTRX＋间歇性低氧组（8只），hTRX腹腔注射每周1次（干预剂量为0．75μg／g体质量）干预，试验共12周。取小鼠胸主动脉，以免疫组织化学和Westernblot法检测TRX、HIF-1和TNF-α表达，比较各组差异。结果间歇性低氧组的TRX、HIF-1和TNF-α显著高于对照组，主要表达在血管外膜。而经hTRX干预后，TRX、HIF-1和TNF—α表达显著低于间歇性低氧组，但高于对照组，各组差异有统计学意义。结论间歇性低氧可导致小鼠胸主动脉外膜TRX、HIF-1和TNF-α表达增加，提示着动脉粥样硬化的风险增加。hTRX对降低HIF-1和TNF-α表达有效，有可能成为一种阻塞性睡眠呼吸暂停综合征的抗氧化治疗手段。

Objective To establish a mouse model of chronic intermittent hypoxia （IH） and observe the changes of expressions of TRX, HIF-1 and TNF-α in thoracic aorta after intervention of hTRX. Methods 24 adult kunming mice were grouped in 3：control group, IH group and hTRX-？ IH group. Long-term intermittent hypoxia test （totally 12 weeks） was proceeded in homemade hypoxia cabin. After the test was finished, horacic aorta of mice were taken and TRX, HIF-1 and TNF-α were detected by Western blot analysis and immunohistochemistry. The results were compared among 3 groups. Results The expression levels of TRX, HIF-1 and TNF-α were significantly higher in IH group than those in control group. However, the expression levels of these indexes were significantly deceased after intervention of hTRX in hTRX＋IH group. Conclusions IH caused the high expression level of TRX, HIF-1 and TNF-α in thoracic aorta of mice, which suggested the high risk of arteriosclerosis. The intervention of hTRX was effective to decrease the expression level of TRX, HIF-1 and TNF-α in thoracic aorta. So hTRX might be a novel antioxidant to reduce complications of OSAS that were linked with oxidative stress and chronic inflammation.