Protective Effect of Antagonist of High-mobility Group Box 1 on Lipopolysaccharide-Induced Acute Lung Injury in Mice
Protective Effect of Antagonist of High-mobility Group Box 1 on Lipopolysaccharide-Induced Acute Lung Injury in Mice
复制标题
DOI：
10.1111/j.1365-3083.2008.02194.x
复制
发表时间：
2009-01-01
影响因子：
3.7
通讯作者：
Bian, Z. -L.
中科院分区：
文献类型：
--
作者：
Gong, Q.;Xu, J. -F.;Bian, Z. -L.
目的：探讨内源性高迁移率族蛋白1(HMGB1)特异性阻断剂重组A盒(Ra盒)对脂多糖(LPS)诱导的急性肺炎症的影响。BALB/c雄性小鼠气管内注射脂多糖(10mU g/只)可成功复制急性肺损伤(ALI)模型。RA-box(0.3，0.6 mg/只，ip)分别于染毒前30min或染毒后2 h给药。各时间点取支气管肺泡灌洗液(BALF)，测定趋化因子、促炎细胞因子、细胞总数和蛋白质含量。结果发现，Ra-box可使BALF中的细胞总数和中性粒细胞数显著减少，W/D值显著降低，蛋白渗漏明显减少。此外，Ra-box还被认为下调了内毒素诱导的趋化因子(角质形成细胞衍生的趋化因子)和促炎细胞因子的表达，包括早期介质TNF-a和晚期介质HMGB1。这些结果证实了Ra-box对内毒素诱导的ALI有明显的保护作用，其作用机制与减少趋化因子和促炎细胞因子的表达有关。
We explored the effects of recombinant A-box (rA-box), a specific blockade for endogenous high mobility group box 1 (HMGB1) protein, on acute lung inflammation induced by lipopolysaccharide (LPS) in vivo. Acute lung injury (ALI) was produced successfully by intratracheal administration of LPS (10 mu g/mouse) in male BALB/c mice. rA-box (0.3, 0.6 mg/mouse, i.p.) was administered 30 min prior to or 2 h after LPS exposure. Bronchoalveolar lavage fluid (BALF) was obtained to measure chemokines, proinflammatory cytokines, total cell counts and proteins at the indicated time points. It was found that rA-box caused a significant reduction in the total cells and neutrophils in BALF, a significant reduction in the W/D ratio and protein leakage at 24 h after LPS challenge. In addition, rA-box was also believed to have downregulated the expression of LPS-induced chemokines (keratinocyte-derived chemokine) and proinflammatory cytokines, including early mediator TNF-a and late mediator HMGB1. These findings confirm the significant protection of rA-box against LPS-induced ALI, and the effect mechanism of rA-box was associated with decreasing the expression of chemokines and proinflammatory cytokines.