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高密度脂蛋白减轻小鼠内毒素性急性肺损伤

肖格磊, 罗自强, 肖宫, 李晨, 熊旭东, 杨莹, 刘惠君

中南大学湘雅医学院2004级学生.湖南,长沙 410078；中南大学湘雅医学院生理学系.湖南,长沙 410078；中南大学湘雅医学院2004级管理办公室.湖南,长沙 410078

摘要

高密度脂蛋白(high density lipoprotein, HDL)是一种血浆含量丰富的脂蛋白，通常认为它可在体内发挥抗炎作用。它能够与内毒素结合而抑制其生物活性。为探讨人HDL对内毒素性急性肺损伤的影响，将昆明小鼠分为假手术对照组、脂多糖(lipopolysaccharide, LPS)组、HDL组和LPS + HDL组，腹腔注射LPS (10 mg/kg体重)复制内毒素性急性肺损伤模型，HDL于腹腔注射LPS 30 min后经尾静脉给予，6 h后结束实验。处死动物前抽取动脉血测定血气变化(PaO_(2), PaO_(2)/FiO_(2), pH, and PaCO_(2))。处死后行支气管肺泡灌洗，计数灌洗中白细胞(white blood cell, WBC)数量，测定总蛋白浓度和乳酸脱氢酶(lactate dehydrogenase, LDH)活性，并取肺进行病理学观察，测定肺组织湿/干重比值、丙二醛(malondialdehyde, MDA)髓过氧化酶(myeloperoxidase, MPO)活性和肿瘤坏死因子--#alpha#(tumor necrosis factor #alpha#, TNF--#alpha#)含量。结果显示：(1) HDL改善小鼠肺换气功能，显著降低LPS所致的PaO_(2)、pH的降低和PaCO_(2)的增高({sl P}<0.01)；(2)HDL显著降低LPS所致的肺泡灌洗液WBC值、总蛋白浓度和LDH活性的增高({sl P}<0.01)，降低肺组织湿/干重比值、MPO活性、MDA和TNF--#alpha#含量({sl P}<0.05, {sl P}<0.01)；(3)病理形态学分析及评分显示，HDL治疗组小鼠在出血、肺水肿及肺组织内中性粒细胞浸润的程度均低于LPS所致肺损伤组({sl P}<0.01)。结果提示，HDL可减轻小鼠内毒素性急性肺损伤。

关键词： 高密度脂蛋白; 急性肺损伤; 内毒素; 肿瘤坏死因子-#alpha#

High--density lipoprotein attenuates lipopolysaccharide--induced acute lung injury in mice

Xiao Gelei, Luo Ziqiang, Xiao Gong, LI Chen, Xiong Xudong, Yang Ying, Liu Huijun

Grade 2004,Xiangya School of Medicine,Central South University.Changsha 410078,Hunan；China；Office of Grade 2004,Xiangya School of Medicine,Central South University.Changsha 410078,Hunan

Abstract

High-density lipoprotein (HDL), an abundant plasma lipoprotein, has been thought to be anti-inflammatory in both health and infectious diseases. It binds lipopolysaccharide (LPS) and neutralizes its bioactivity. The present study aimed to investigate the potential role of HDL, which was separated from human plasma, in LPS-induced acute lung injury in mice. Kunming mice (18-22 g) were treated with either HDL (70 mg/kg body weight, via tail vein) or saline 30 min after LPS administration (10 mg/kg body weight, intraperitoneally) and were decapitated 6 h after LPS challenge. The arterial blood was collected and analyzed for blood gas variables (PaO_(2), pH, and PaCO_(2)). The bronchoalveolar lavage fluid (BALF) samples were analyzed for total protein concentrateion, lactate dehydrogenase (LDH) activity, and white blood cell (WBC) count. The lung samples were taken for histopathological evaluation and for determination of wet-to-dry weight ratio (W/D) of lung weight, malondialdehyde (MDA) content, myeloperoxidase (MPO) activity and tumor necrosis factor 冄 (TNF-#alpha#) content. Arterial blood gas analysis showed that after LPS challenge, HDL-treated mice exhibited a higher PaO_(2), and pH, but a lower PaCO_(2) than control ones (P<0.01). LPS-induced increases in total protein concentration, WBC number and LDH activity in BALF were significantly attenuated in HDL-treated mice (P<0.01). HDL treatment also resulted in a significant protection of lung tissues against LPS-induced acute lung injury via decreasing W/D ratio, MPO activity, MDA content, and via decreasing the content of the pro-inflammatory cytokine TNF-#alpha# (P<0.05, P<0.01). Histological examination revealed that HDL treatment resulted in significantly lower scores of acute lung injury induced by LPS with reduced hemorrhage, intra-alveolar edema, and neutrophilic infiltration (P<0.01). It is suggested that HDL plays a protective role in attenuating LPS-induced acute lung injury in mice.

Key words: high-density lipoprotein;acute lung injury;lipopolysaccharide;tumor necrosis factor #alpha#

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引用本文：

肖格磊, 罗自强, 肖宫, 李晨, 熊旭东, 杨莹, 刘惠君. 高密度脂蛋白减轻小鼠内毒素性急性肺损伤[J]. 生理学报 2008; 60 (3): 403-408.

Xiao Gelei, Luo Ziqiang, Xiao Gong, LI Chen, Xiong Xudong, Yang Ying, Liu Huijun. High--density lipoprotein attenuates lipopolysaccharide--induced acute lung injury in mice. Acta Physiol Sin 2008; 60 (3): 403-408 (in Chinese with English abstract).