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基础药物对小鼠急性肺损伤预后的影响。

Effects of basic drugs on prognosis of acute lung injury in mice.

作者信息

Jia Liming, Ren Junming, Zhang Weiwei, Qi Yuehong, Zheng Lina, Guo Yongqing

机构信息

Department of Anesthesiology, The People's Hospital of Shanxi Province Taiyuan 030012, China.

Department of Anesthesiology of Shanxi Medical University Taiyuan 030012, China.

出版信息

Int J Clin Exp Med. 2015 Oct 15;8(10):19079-85. eCollection 2015.

Abstract

The aim of this study was to investigate the effects of basic drugs that alkalizes blood, on prognosis of acute lung injury in mice. Mice were randomized into three groups: Group normal saline, Group THAM, injected with 3.64% tri-(hydroxymethyl) methylamine (THAM), and Group NaHCO3, injected with 5% NaHCO3 (n=26, each group). The acute lung injury model was established by intraperitoneal injection of lipopolysaccharide (LPS; 50 mg/kg), followed by infusion of varying concentrations of the above solution into tail vein at the rate of 0.5 ml/h (controlled by micro pump) for over 2 h. Thirty minutes later, 6 mice from each group were randomly selected for blood gas analysis; then, the mice were killed and their lung tissues were sampled for detection of relative indicators, and the remaining mice were observed for signs of mortality for 72 h. Arterial pH, bicarbonate (HCO3 (-)), and BE and mortality of group THAM and NaHCO3 increased significantly compared to the corresponding parameters of the group normal saline (P<0.05); compared to the group normal saline, group NaHCO3 had increased blood [Na(+)] and decreased [K(+)] and [Ca(2+)] (P<0.05). Blood [Na(+)] of group THAM decreased while the lactic acid concentration increased (P<0.05) compared to the corresponding values of the group normal saline. Malondialdehyde (MDA) and myeloperoxidase (MPO) activity and wet-to-dry lung weight ratio (W/D) of group THAM and NaHCO3 increased significantly relative to group normal saline (P<0.05). Compared with the biopsy results of (A), pathological biopsy of (B) and (C) clearly revealed alveolar wall thickening, edema of alveolar epithelial cells, and infiltration of large neutrophils. Alkalizing blood could neither inhibit inflammatory reactions in LPS mouse model nor reduce the mortality rate of mice with acute lung injury, while excessive alkalization of blood could increase mice mortality.

摘要

本研究旨在探讨血液碱化基础药物对小鼠急性肺损伤预后的影响。将小鼠随机分为三组:生理盐水组、THAM组(注射3.64%三(羟甲基)甲胺(THAM))和NaHCO₃组(注射5% NaHCO₃,每组n = 26)。通过腹腔注射脂多糖(LPS;50 mg/kg)建立急性肺损伤模型,随后以0.5 ml/h的速率(由微量泵控制)经尾静脉输注不同浓度的上述溶液,持续2 h以上。30分钟后,每组随机选取6只小鼠进行血气分析;然后处死小鼠,取肺组织样本检测相关指标,其余小鼠观察72 h的死亡体征。与生理盐水组相应参数相比,THAM组和NaHCO₃组的动脉pH、碳酸氢盐(HCO₃⁻)、碱剩余(BE)及死亡率显著升高(P < 0.05);与生理盐水组相比,NaHCO₃组血[Na⁺]升高,[K⁺]和[Ca²⁺]降低(P < 0.05)。与生理盐水组相应值相比,THAM组血[Na⁺]降低而乳酸浓度升高(P < 0.05)。与生理盐水组相比,THAM组和NaHCO₃组的丙二醛(MDA)、髓过氧化物酶(MPO)活性及肺湿/干重比(W/D)显著升高(P < 0.05)。与(A)的活检结果相比,(B)和(C)的病理活检清楚显示肺泡壁增厚、肺泡上皮细胞水肿及大量中性粒细胞浸润。血液碱化既不能抑制LPS小鼠模型中的炎症反应,也不能降低急性肺损伤小鼠的死亡率,而血液过度碱化会增加小鼠死亡率。

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