Effects of intratracheal tumor necrosis factor-alpha plasmid vector on lipopolysaccharide lethality and lung injury in mice.
Effects of intratracheal tumor necrosis factor-alpha plasmid vector on lipopolysaccharide lethality and lung injury in mice.
复制标题
气管内肿瘤坏死因子-α质粒载体对小鼠脂多糖致死率和肺损伤的影响。
DOI：
10.1080/01902140490517791
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发表时间：
2004
影响因子：
1.7
通讯作者：
Jackson,RobertM
中科院分区：
文献类型：
--
作者：
Wright,MarcienneM;Powell,CharlesS;Jackson,RobertM
细菌脂多糖（LPS）可导致急性肺损伤（ALI），并导致急性呼吸窘迫综合征（ARDS）和败血症中的炎症，使得对LPS的抵抗机制在临床环境中至关重要。作者推测，腹腔注射编码大鼠肿瘤坏死因子-α（TNF-α）的质粒（pcDNA3.0-rTNFα）可增加小鼠对LPS诱导的ALI或死亡的抵抗力。他们研究了C57/BL 6小鼠中LPS诱导的ALI发展的时间过程和剂量反应，并在LPS攻击前1、2或3周内注射100 μg pcDNA3.0-rTNFα可能的保护作用。腹腔内（IP）LPS攻击后48小时，肺髓过氧化物酶（MPO）活性和肺泡灌洗液（BALF）细胞计数显著增加。经pcDNA3.0-rTNFα预处理后，LPS攻击小鼠的肺/体重比低于pcDNA3.0治疗组小鼠，但其他肺损伤指标无差异。与用对照载体pcDNA3.0预处理的小鼠相比，经腹腔内注射pcDNA3.0-rTNFα载体2周后用致死性IP LPS攻击的小鼠的存活率显著提高。然而，pcDNA3.0预处理的小鼠耐受LPS攻击不如盐水预处理的对照。LPS可引起嗜肺细胞的肺损伤和死亡，而pcDNA3.0-TNFα不能预防LPS引起的ALI。与pcDNA3.0预处理组相比，pcDNA3.0-rTNFα腹腔内预处理组小鼠LPS攻击后的存活率明显提高。
Bacterial lipopolysaccharide (LPS) causes acute lung injury (ALI) and contributes to inflammation in the acute respiratory distress syndrome (ARDS) and sepsis, making mechanisms of resistance to LPS critically important in clinical settings. The authors postulated that intratracheal administration of a plasmid (pcDNA3.0-rTNFα) encoding rat tumor necrosis factor-alpha (TNF-α) would increase resistance of mice to LPS-induced ALI or mortality. They investigated the time course and dose-response for development of LPS-induced ALI in C57/BL6 mice and sought possible protective effects of 100 µg pcDNA3.0-rTNFα intratracheally 1, 2, or 3 weeks before LPS challenge. Lung myeloperoxidase (MPO) activity and alveolar lavage fluid (BALF) cell counts increased significantly 48 hours after intraperitoneal (IP) LPS challenges. After pcDNA3.0-rTNFα pretreatment, mice challenged with LPS had lower lung/body weight ratios than mice treated with pcDNA3.0; however, other indices of lung injury did not differ. Survival of mice challenged with lethal IP LPS 2 weeks after intratracheal pcDNA3.0-rTNFα vector improved significantly, compared to mice pretreated with the control vector, pcDNA3.0. However, pcDNA3.0-pretreated mice tolerated LPS challenge less well than saline-pretreated controls. LPS causes neutrophilic lung injury and mortality, but pcDNA3.0-TNFα does not prevent ALI due to LPS. Intratracheal pcDNA3.0-rTNFα pretreatment significantly improves survival of mice after LPS challenge, compared to those pretreated with pcDNA3.0.