Bi Ming-hua, Wang Bao-en, Schafer Martina, Mayer Konstantin, Zhang Shu-wen, Li Min, Wang Hui-ji
Medical and Health Center, Beijing Friendship Hospital Affiliated to the Capital University of Medical Science, Beijing 100050, China.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2006 Dec;18(12):711-5.
To assess the effect of Clinoleic 20% (olive oil-based, n-9) and Lipoven 20% (soy bean-based, n-6) lipid emulsions on inflammatory parameters in a murine acute lung injury (ALI) model induced by lipopolysaccharide (LPS) of E. coli O111:B4.
Male Balb/C mice were infused for three days with 0.9% NaCl, Clinoleic 20%, or Lipoven 20% respectively, and sacrificed either at 8 hours or 24 hours after intra-tracheal introduction of LPS. Survival rate, lung wet/dry weight ratio (W/D), lung tissue myeloperoxidase (MPO) activity were determined, and tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage fluid (BALF) were determined with enzyme linked immunosorbent assay (ELISA). Serum free fatty acids [arachidonic acid (AA), oleic acid, linoleic acid] were determined by gas chromatography. Leukocytes in BALF were counted under light microscope.
Lipoven significantly decreased survival rate at 24 hours after intra-tracheal LPS challenge compared to corresponding controls (both P<0.01). No significant difference was observed between Clinoleic and NaCl groups. MPO activity was obviously increased in lipids groups than that in NaCl group at 24 hours (both P<0.01), and no difference was found between two lipids groups. LPS markedly induced an increase in leukocyte infiltration, W/D ratio, lung MPO activity, release of TNF-alpha as well as MIP-2 into alveolar space in both lipids and NaCl groups. Pre-infusion with Lipoven gave rise to heavier leukocyte infiltration at 24 hours, which was blunted in Clinoleic group and NaCl group (both P<0.01). In contrast to Clinoleic and NaCl groups, Lipoven increased production of TNF-alpha at 24 hours and MIP-2 at 8 hours in LPS-treated mice (all P<0.01). Notably, lipid emulsions increased LPS-induced MPO activity, but no difference in effects was found in both Lipoven and Clinoleic groups. Clinoleic significantly reduced free AA at 8 and 24 hours compared with Lipoven (both P<0.01). There were no differences in lung tissues edema, serum oleic acid and linoleic acid among three groups.
In murine model of ALI, although LPS caused an increase in alveolar leucocytic infiltration, MPO activity, cytokine generation in both lipids and NaCl groups, Lipoven 20%, n-6 lipid emulsion induces a severer inflammatory reaction. It is speculated that by increasing AA, Lipoven 20% may aggravate ALI, whereas Clinoleic 20%, n-9 lipid emulsion possibly offers an alternative choice in producing less impact on inflammatory lung injury.
评估20% Clinoleic（基于橄榄油，n-9）和20% Lipoven（基于大豆油，n-6）脂质乳剂对大肠杆菌O111:B4脂多糖（LPS）诱导的小鼠急性肺损伤（ALI）模型中炎症参数的影响。
雄性Balb/C小鼠分别连续三天输注0.9%氯化钠、20% Clinoleic或20% Lipoven，在气管内注入LPS后8小时或24小时处死。测定存活率、肺湿/干重比（W/D）、肺组织髓过氧化物酶（MPO）活性，并用酶联免疫吸附测定（ELISA）法测定支气管肺泡灌洗液（BALF）中的肿瘤坏死因子-α（TNF-α）和巨噬细胞炎性蛋白-2（MIP-2）。通过气相色谱法测定血清游离脂肪酸[花生四烯酸（AA）、油酸、亚油酸]。在光学显微镜下对BALF中的白细胞进行计数。
与相应对照组相比，气管内LPS攻击后24小时，Lipoven显著降低了存活率（均P<0.01）。Clinoleic组和氯化钠组之间未观察到显著差异。24小时时，脂质组的MPO活性明显高于氯化钠组（均P<0.01），两个脂质组之间未发现差异。LPS显著诱导脂质组和氯化钠组的白细胞浸润增加、W/D比值增加、肺MPO活性增加、TNF-α以及MIP-2释放到肺泡腔中。预先输注Lipoven导致24小时时白细胞浸润更严重，而Clinoleic组和氯化钠组则减轻（均P<0.01）。与Clinoleic组和氯化钠组相比，Lipoven增加了LPS处理小鼠24小时时TNF-α的产生以及8小时时MIP-2的产生（均P<0.01）。值得注意的是，脂质乳剂增加了LPS诱导的MPO活性，但Lipoven组和Clinoleic组在作用效果上没有差异。与Lipoven相比，Clinoleic在8小时和24小时时显著降低了游离AA水平（均P<0.01）。三组之间肺组织水肿、血清油酸和亚油酸没有差异。
在ALI小鼠模型中，尽管LPS导致脂质组和氯化钠组的肺泡白细胞浸润增加、MPO活性增加、细胞因子生成增加，但20% Lipoven（n-6脂质乳剂）诱导了更严重的炎症反应。推测20% Lipoven可能通过增加AA加重ALI，而20% Clinoleic（n-9脂质乳剂）可能在对炎症性肺损伤产生较小影响方面提供了一种替代选择。
