内皮细胞特异性分子-1对内毒素致小鼠急性肺损伤时炎症反应的影响

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摘要目的：探讨内皮细胞特异性分子-1（Endocan）对内毒素诱导的急性肺损伤（ALI）小鼠的保护作用及其机制。方法：将30只C57BL/6小鼠随机分为Control组、脂多糖（LPS）组和Endocan组，每组10只，LPS组和Endocan组采用LPS雾化吸入法（400 μg/mL）30 min，Control组雾化吸入等量0.9%氯化钠溶液，Endocan组于实验前30 min腹腔注射Endocan 0.25 mg/kg，造模24 h后处死小鼠。检测肺湿/干重比（W/D）、髓过氧化物酶（MPO）；酶联免疫吸附法（ELISA）检测小鼠肺泡灌洗液（BALF）中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和细胞间黏附分子1（ICAM-1）；电镜观察肺组织超微结构改变。结果：与Control组比，LPS组W/D、MPO、TNF-α、IL-6和ICAM-1均明显升高[W/D：5.62±0.95 vs. 4.08±0.76， MPO（U/g）：2.71±0.59 vs. 1.39±0.28，TNF-α（pg/mL）：140.36±10.01 vs. 79.65±6.23，IL-6（pg/mL）：156.54± 17.82 vs. 50.11±6.02，ICAM-1（pg/mL）：107.05±13.92 vs. 57.31±8.02，P＜0.01]；应用Endocan干预后，Endocan组W/D、MPO、TNF-α、IL-6和ICAM-1较LPS组显著下降[W/D：4.38±0.47 vs. 5.62±0.95，MPO（U/g）：1.84±0.42 vs. 2.71±0.59，TNF-α（pg/mL）：113.07±8.49 vs. 140.36±10.01，IL-6（pg/mL）：123.22± 12.80 vs. 156.54±17.82，ICAM-1（pg/mL）：89.44±10.92 vs. 107.05±13.92，P＜0.01]，电镜下超微结构改变明显减轻。结论：Endocan可明显减轻LPS诱导的ALI小鼠肺组织的炎症反应，提示Endocan在ALI中具有保护作用。

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	张晓隆
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关键词 ：内皮细胞特异分子-1, 脂多糖类, 急性呼吸窘迫综合征, 小鼠

Abstract：Objective: To investigate the effect of Endocan on lipopolysaccharide (LPS) induced acute lung injury (ALI). Methods: LPS was used to construct C57BL/6 mice ALI model by aerosol inhalation for 30 min, and Endocan was injected intraperitoneally at 30 min prior to LPS exposure. Mice in control group were treated with normal saline at an equal volume. The mice were sacrificed 24 h after aerosol inhalation. The ratio of lung wet weight to dry weight (W/D) was measured to assess the extent of pulmonary edema. Myeloperoxidase (MPO) activity in lung tissues was measured to determine Neutrophil infiltration. The level of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α) and interleukins-6 (IL-6) in bronchoalveolar lavage fluid (BALF) were detected by ELISA. The ultrastructural changes were visualized by electron microscope. Results: Compared with the control group, the lung W/D, MPO activity and the concentrations of TNF-α, IL-6 and ICAM-1 were dramatically increased in LPS group [W/D: 5.62±0.95 vs. 4.08±0.76, MPO (U/g): 2.71±0.59 vs. 1.39±0.28, TNF-α (pg/mL): 140.36±10.01 vs. 79.65±6.23, IL-6 (pg/mL): 156.54±17.82 vs. 50.11±6.02, ICAM-1 (pg/mL): 107.05±13.92 vs. 57.31±8.02, P<0.01] which could be relieved by Endocan treatment [W/D: 4.38±0.47 vs. 5.62±0.95, MPO (U/g): 1.84±0.42 vs. 2.71±0.59, TNF-α (pg/mL): 113.07±8.49 vs. 140.36±10.01, IL-6 (pg/mL): 123.22±12.80 vs. 156.54±17.82, ICAM-1 (pg/mL): 89.44±10.92 vs. 107.05±13.92, P<0.01]. Electron microscope data showed obvious ultrastructure injury induced by LPS, which was greatly attenuated in Endocan group. Conclusion: Endocan can suppress inflammatory response in endotoxin-induced acute lung injury, which suggests that Endcan may be a potential protective agent for ALI.

Key words： Endocan lipopolysaccharides acute respiratory distress syndrome mice

收稿日期: 2017-11-07

基金资助:国家自然科学基金资助项目（30772088）；温州市科技局科研基金资助项目（Y20140670）。

通讯作者: 吴成云，副主任医师，Email：wcy857516126@163.com。

作者简介: 张晓隆（1971-），男，浙江乐清人，主治医师，硕士。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2018/V48/I9/636

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