脂多糖诱导的大鼠血清中白细胞介素-6肿瘤坏死因子-α前列腺素E_2含量及分泌型磷脂酶A_2活性的变化

Kinetics of serum interleukin6,tumor necrosis factorα,prostaglandin E 2 levels and secretary phospholipase A 2 activity in rats treated by lipopolysaccharide

目的：研究内毒素血症大鼠血中促炎性细胞因子白细胞介素 ６（ Ｉ Ｌ ６）、肿瘤坏死因子 α（ Ｔ Ｎ Ｆ α）及花生四烯酸代谢产物前列腺素 Ｅ２ （ Ｐ Ｇ Ｅ２）的含量和血中分泌型磷脂酶 Ａ２ （ｓ Ｐ Ｌ Ａ２）活性产生的动态变化规律，探讨脂多糖（ Ｌ Ｐ Ｓ）全面启动机体炎症反应的机制。方法：采用大鼠腹腔注射 Ｌ Ｐ Ｓ复制大鼠急性内毒素血症模型，分别动态测定了正常大鼠和急性内毒素血症大鼠血清中 Ｉ Ｌ ６、 Ｔ Ｎ Ｆ α、 Ｐ Ｇ Ｅ２ 含量及ｓ Ｐ Ｌ Ａ２ 活性。结果： Ｌ Ｐ Ｓ注射后，大鼠血清中 Ｉ Ｌ ６、 Ｔ Ｎ Ｆ α、 Ｐ Ｇ Ｅ２ 含量及ｓ Ｐ Ｌ Ａ２ 活性均显著升高（与正常组比较 Ｐ＜ ００５ 或 Ｐ＜００１ ）， Ｔ Ｎ Ｆ α最先升高，在 ４５ 分钟达峰值并呈双相变化，ｓ Ｐ Ｌ Ａ２ 和 Ｐ Ｇ Ｅ２ 达峰值时间（１５ 小时）晚于 Ｔ Ｎ Ｆ α，并分别呈双相及三相变化； Ｉ Ｌ ６ 缓慢升高于 ６ 小时达峰值并呈单相变化。相关性分析显示， Ｔ Ｎ Ｆ α含量升高与ｓ Ｐ Ｌ Ａ２ 活性升高呈正相关（ｒ＝ ０８１９ ６， Ｐ＜ ００５）。结论： Ｌ Ｐ Ｓ可明显引发机体内的早期细胞因子反应，通过迅速激活ｓ Ｐ Ｌ Ａ２ ，促进花生四烯酸代谢，使脂类介质产生增加，可?

Objective:To study the kinetics of the levels of proinflammatory cytokines interleukin6 (IL6) ,tumor necrosis factorα(TNFα) and arachidonic acid metabolites,as well as the activity of secretary phospholipase A 2 (sPLA 2) in rats treated with lipopolysaccharide (LPS).Methods:Acute endotoxemia in rats were produced by intraperitoneal injection of LPS (2 mg/kg),serum samples were collected in various time points and the contents of IL6,TNFα,prostaglandin E 2(PGE 2) and the activity of sPLA 2 were determined.Results:Following LPS administration,the concentrations of IL6,TNFα,PGE 2 and the activity of sPLA 2 increased significantly compared to normal controls,but these changes showed different patterns during 24 hours.TNFα levels elevated earlier and reached its peak value at 45 minutes after LPS treatment,while sPLA 2 activity and PGE 2 level reached their peak values at 1 5 hours,respectively.The elevation of TNFα and sPLA 2 showed biphase patterns while PGE 2 had a triphase one.The level of IL6 increased slowly and reached its peak value at 6 hours after LPS treatment,showing a monophase response.The significant correlation between TNFα levels and sPLA 2 activity ( r =0 819 6, P <0 05) indicated that TNFα might activate sPLA 2.Conclusions:LPS can initiate the early cytokine response in vivo and promote arachidonic acid metabolism as well as lipid mediator production through rapid sPLA 2 activation,which would be the important initiative factor during septic shock,even multiple organ dysfunction syndrome(MODS).TNFα might be the key cytokine in the pathogenesis of early sPLA 2 activation.