Recombinant human thioredoxin suppresses lipopolysaccharide-induced bronchoalveolar neutrophil infiltration in rat
Recombinant human thioredoxin suppresses lipopolysaccharide-induced bronchoalveolar neutrophil infiltration in rat
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DOI：
10.1016/j.lfs.2006.03.026
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发表时间：
2006-08-15
期刊：
影响因子：
6.1
通讯作者：
Nakamura, Hajime
中科院分区：
文献类型：
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作者：
Ueda, Shugo;Nakamura, Takayuki;Nakamura, Hajime
人硫氧还蛋白(Trx)是一种多功能氧化还原活性蛋白。我们之前曾报道，重组人硫氧还蛋白(RhTRX)可以减轻炎症细胞因子或博莱霉素诱导的小鼠肺损伤。本研究分析了大鼠静脉注射脂多糖(LPS)后静脉注射重组人TRX的作用。大鼠注射脂多糖后给予重组人TRX治疗。尽管团注没有保护作用，但持续静脉注射rhTRX显著抑制了支气管肺泡灌洗液中中性粒细胞的百分比。组织学检查还显示，rhTRX减少了肺组织中中性粒细胞的浸润。给药后，rh TRX主要通过尿液排泄，肺组织蓄积较少。在这个模型中，脂多糖诱导的肺内氧化应激很轻微。这些结果表明，持续静脉注射rh TRX可通过抗趋化作用抑制脂多糖诱导的支气管肺泡中性粒细胞的浸润。在异种移植模型中，给予rhTRX没有促进肿瘤生长，也没有影响化疗敏感性，提示rhTRX治疗癌症患者是安全的。(C)2006 Elsevier Inc.保留所有权利。
Human thioredoxin (TRX) is a multifunctional redox-active protein. We previously reported that the intraperitoneal administration of recombinant human thioredoxin (rhTRX) attenuates inflammatory cytokine- or bleomycin-induced lung injury in mice. In this study, the effect of rhTRX injected intravenously after lipopolysaccharide (LPS) injection was analyzed in rats. Rats were injected with LPS followed by treatment with rhTRX. Although the bolus injection exerted no protective effect, continuous intravenous administration of rhTRX significantly suppressed percentage number of neutrophils in bronchoalveolar lavage fluid. Histological examination also showed that rhTRX decreased neutrophil infiltration in the lung tissues. Administered rhTRX was mainly excreted into the urine and the tissue accumulation of rhTRX in the lung was marginal. LPS-induced oxidative stress in the lung was slight in this model. These results demonstrated that continuous intravenous administration of rhTRX suppresses LPS-induced bronchoalveolar neutrophil infiltration by an anti-chemotactic effect. Administration of rhTRX did not promote the tumor growth nor affect chemosensitivity in the xenotransplantation model, suggesting the safety of rhTRX therapy for cancer patients. (c) 2006 Elsevier Inc. All rights reserved.