Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.
J Pediatr Surg. 2010 Dec;45(12):2412-8. doi: 10.1016/j.jpedsurg.2010.08.044.
Long-term total parenteral nutrition (TPN) in children is often complicated by parental nutrition-associated liver disease and may even lead to liver failure. Recently, the addition of ω-3 fatty acids to TPN has been shown to reduce the risk of parental nutrition-associated liver disease. The purpose of this study was to explore the anti-inflammatory effects of ω-3 fatty acids (eicosapentaenoic acid [EPA]) to demonstrate the protection of the liver against hepatic steatosis and damage.
Lipopolysaccharide (LPS) and prostaglandin E(2) (PGE(2)) were used to stimulate human macrophages and hepatocytes (THLE-3) to induce in vitro inflammatory condition. The cells were then incubated with either ω-3 (EPA) or ω-6 (arachidonic acid) fatty acids. Supernatants were collected at different time points for the measurement of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin 10 (IL-10) using enzyme-linked immunosorbent assay. Furthermore, pretreated macrophages by LPS stimulation and after incubation with EPA were added to prestimulated hepatocytes for the subsequent measurement of cytokine response.
Eicosapentaenoic acid effectively reduced LPS-induced or PGE(2)-induced TNF-α and IL-6 expression, and increased IL-10 expression significantly when compared with arachidonic acid. Furthermore, supernatant collected after co-culturing EPA with macrophages also suppressed the levels of TNF-α and IL-6 in hepatocytes. This would suggest that EPA not only had an anti-inflammatory effect on macrophages and hepatocytes directly, it could indirectly reduce hepatocyte inflammation through activated macrophages.
The addition of ω-3 fatty acids in TPN suppresses the inflammatory response via direct and indirect routes. The findings may help explain the clinical benefits of EPA in pediatric patients receiving long-term TPN.
儿童长期全胃肠外营养（TPN）常并发与肠外营养相关的肝病，甚至可能导致肝功能衰竭。最近，TPN 中添加ω-3 脂肪酸已被证明可降低与肠外营养相关的肝病风险。本研究旨在探讨 ω-3 脂肪酸（二十碳五烯酸[EPA]）的抗炎作用，以证明其对肝脂肪变性和损伤的保护作用。
使用脂多糖（LPS）和前列腺素 E（2）（PGE（2））刺激人巨噬细胞和肝细胞（THLE-3），诱导体外炎症状态。然后，将细胞分别与 ω-3（EPA）或 ω-6（花生四烯酸）脂肪酸孵育。在不同时间点收集上清液，通过酶联免疫吸附试验测量肿瘤坏死因子 α（TNF-α）、白细胞介素 6（IL-6）和白细胞介素 10（IL-10）。此外，用 LPS 刺激巨噬细胞，然后用 EPA 预处理，加入预先刺激的肝细胞，以测量随后的细胞因子反应。
与花生四烯酸相比，二十碳五烯酸可有效降低 LPS 诱导或 PGE（2）诱导的 TNF-α和 IL-6 的表达，并显著增加 IL-10 的表达。此外，收集 EPA 与巨噬细胞共培养后的上清液也可抑制 TNF-α和 IL-6 在肝细胞中的水平。这表明 EPA 不仅对巨噬细胞和肝细胞有直接的抗炎作用，还可以通过激活的巨噬细胞间接减少肝细胞的炎症反应。
TPN 中添加 ω-3 脂肪酸通过直接和间接途径抑制炎症反应。这些发现可能有助于解释 EPA 在接受长期 TPN 的儿科患者中的临床益处。
