Lysophosphatidylcholine Containing Docosahexaenoic Acid at the sn-1 Position is Anti-inflammatory
Lysophosphatidylcholine Containing Docosahexaenoic Acid at the sn-1 Position is Anti-inflammatory
复制标题
DOI：
10.1007/s11745-010-3392-5
复制
发表时间：
2010-03-01
期刊：
影响因子：
1.9
通讯作者：
Kim, Mee Ree
中科院分区：
文献类型：
--
作者：
Huang, Long Shuang;Hung, Nguyen Dang;Kim, Mee Ree
已知溶血磷脂酰胆碱是多种细胞反应中的脂质介质。在这项研究中，我们研究了含有二十二碳六烯酸在sn-1位酯化的溶血磷脂酰胆碱的抗炎作用。首先，在RAW 264.7细胞中，DHA-lysoPtdCho浓度依赖性地抑制LPS诱导的NO形成。然而，ARA-lysoPtdCho显示部分抑制，LNA-lysoPtdCho没有显著影响。此外，DHA-lysoPtdCho还降低了TNF-α或IL-6的水平，但不降低PGE的水平（2）。在动物实验中，ARA-lysoPtdCho（150或500 μ g/kg）的静脉内给药显著地防止酵母聚糖A诱导的血浆渗漏，最大功效（Emax）为50%，与LNA-lysoPtdCho的无效相反。值得注意的是，DHA-lysoPtdCho抑制了酵母聚糖A诱导的血浆渗漏，ED 50值为46 μ g/kg，Emax值约为95%。此外，机制研究表明，DHA-lysoPtdCho的抗炎作用部分与LTC 4、TNF-α和IL-6的形成减少有关。当lysoPtdCho给药和酵母聚糖A激发之间的间隔时间延长至2小时时，DHA-lysoPtdCho的这种抑制作用增强，表明DHA-lysoPtdCho代谢产物对于抗炎作用是重要的。为了支持这一点，17-HPDHA-lysoPtdCho显示出比DHA-lysoPtdCho更大的抗炎作用。此外，腹膜内给予DHA-lysoPtdCho或17（S）-氢过氧衍生物也观察到类似的抗炎作用。此外，口服DHA-lysoPtdCho也表现出显著的抗炎作用。综上所述，提出DHA-lysoPtdCho及其代谢产物可能是体内系统中的抗炎脂质。
Lysophosphatidylcholine is known to be a lipid mediator in various cellular responses. In this study, we examined the anti-inflammatory actions of lysophosphatidylcholine containing docosahexaenoic acid esterified at the sn-1 position. First, in RAW 264.7 cells, DHA-lysoPtdCho suppressed the LPS-induced formation of NO concentration-dependently. However, ARA-lysoPtdCho showed a partial suppression, and LNA-lysoPtdCho had no significant effect. Additionally, DHA-lysoPtdCho also reduced the level of TNF-alpha or IL-6, but not PGE(2). In animal experiments, the i.v. administration of ARA-lysoPtdCho (150 or 500 mu g/kg) prevented zymosan A-induced plasma leakage remarkably with a maximal efficacy (Emax) of 50%, in contrast to no effect with LNA-lysoPtdCho. Remarkably, DHA-lysoPtdCho suppressed zymosan A-induced plasma leakage with an ED50 value of 46 mu g/kg and an Emax value of around 95%. Additionally, mechanistic studies indicated that the anti-inflammatory action of DHA-lysoPtdCho was partially related to the reduced formation of LTC4, TNF-alpha, and IL-6. When the interval time between lysoPtdCho administration and zymosan A challenge was extended up to 2 h, such a suppressive action of DHA-lysoPtdCho was augmented, suggesting that a DHA-lysoPtdCho metabolite is important for anti-inflammatory action. In support of this, 17-HPDHA-lysoPtdCho showed a greater anti-inflammatory action than DHA-lysoPtdCho. Furthermore, a similar anti-inflammatory action was also observed with i.p. administration of DHA-lysoPtdCho or a 17(S)-hydroperoxy derivative. Additionally, oral administration of DHA-lysoPtdCho also expressed a significant anti-inflammatory action. Taken together, it is proposed that DHA-lysoPtdCho and its metabolites may be anti-inflammatory lipids in vivo systems.