Yan Yi-Jie, Li Yue, Lou Bin, Wu Man-ping
Department of Biochemistry, School of Pharmacy, Fudan University, Shanghai, 200032, China.
Life Sci. 2006 Jun 6;79(2):210-5. doi: 10.1016/j.lfs.2006.02.011. Epub 2006 Mar 6.
High density lipoprotein (HDL) binds lipopolysaccharide (LPS) and neutralizes its toxicity. The aim of our study was to investigate the effects of Apolipoprotein (ApoA-I), the major apolipoprotein of HDL, on LPS-induced acute lung injury (ALI) and endotoxemia. BALB/c mice were challenged with LPS, followed by ApoA-I or saline administration for 24h. The mice were then sacrificed and histopathological analysis of the lung was performed. We found that ApoA-I could attenuate LPS-induced acute lung injury and inflammation. To investigate the mechanisms, we measured tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) levels in the serum and bronchoalveolar lavage (BAL) fluid and found that ApoA-I could significantly inhibit LPS-induced increases in the IL-1beta and TNF-alpha levels in serum (P<0.05, respectively), as well as in the IL-1beta, TNF-alpha, and IL-6 levels in BAL fluid (P<0.01 and P<0.05, P<0.05, respectively). Moreover, we evaluated the effect of ApoA-I on the mortality of L-929 cells which were attacked by LPS-activated peritoneal macrophages. We found that ApoA-I could significantly inhibit the LPS-induced cell death in a dose-dependent fashion. Furthermore, we investigated in vivo the effects of ApoA-I on the mortality rate and survival time after LPS administration and found that ApoA-I significantly decreased the mortality (P<0.05) and increased the survival time (P<0.05). In summary, the results suggest that ApoA-I could effectively protect against LPS-induced endotoxemia and acute lung damage. The mechanism might be related to inhibition of inflammatory cytokine release from macrophages.
高密度脂蛋白（HDL）可结合脂多糖（LPS）并中和其毒性。我们研究的目的是探讨HDL的主要载脂蛋白载脂蛋白A-I（ApoA-I）对LPS诱导的急性肺损伤（ALI）和内毒素血症的影响。用LPS攻击BALB/c小鼠，随后给予ApoA-I或生理盐水24小时。然后处死小鼠并对肺进行组织病理学分析。我们发现ApoA-I可减轻LPS诱导的急性肺损伤和炎症。为了探究其机制，我们检测了血清和支气管肺泡灌洗（BAL）液中肿瘤坏死因子α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的水平，发现ApoA-I可显著抑制LPS诱导的血清中IL-1β和TNF-α水平升高（分别为P<0.05），以及BAL液中IL-1β、TNF-α和IL-6水平升高（分别为P<0.01、P<0.05、P<0.05）。此外，我们评估了ApoA-I对受LPS激活的腹腔巨噬细胞攻击的L-929细胞死亡率的影响。我们发现ApoA-I可显著以剂量依赖方式抑制LPS诱导的细胞死亡。此外，我们在体内研究了ApoA-I对LPS给药后死亡率和存活时间的影响，发现ApoA-I显著降低了死亡率（P<0.05）并延长了存活时间（P<0.05）。总之，结果表明ApoA-I可有效预防LPS诱导的内毒素血症和急性肺损伤。其机制可能与抑制巨噬细胞释放炎性细胞因子有关。
