Department of Intensive Care Unit, the First Affiliated Hospital, China Medical University, Bei-er Road 92, Shenyang, 110001, Liaoning Province, People's Republic of China.
Inflammation. 2013 Dec;36(6):1201-8. doi: 10.1007/s10753-013-9656-5.
The present study aimed to determine the protective effects and the underlying mechanisms of unfractionated heparin on lipopolysaccharide (LPS)-induced endotoxemia and lung injury in rats. Rats were injected intravenously with LPS at 6 mg/kg. We examined the therapeutic effects of unfractionated heparin (100 or 300 U/kg) on LPS-induced endotoxemia by dosing intravenously simultaneously after LPS challenge. The animal lung edema degree was evaluated by wet/dry weight ratio. The levels of inflammatory mediators including interleukin-1β (IL-1β) and interleukin-6 (IL-6) were assayed by enzyme-linked immunosorbent assay and quantitative real-time RT-PCR. The activation of nuclear factor-κB (NF-κB) was evaluated by Western blotting. The investigations revealed that treatment with unfractionated heparin can attenuate inflammatory responses in a rat model of LPS-induced acute lung injury, and the effect was much better in 300 U/kg group. The mechanisms by which unfractionated heparin exerts its anti-inflammatory effect are correlated with inhibition of IL-1β and IL-6 production via inactivation of NF-κB.
本研究旨在探讨未分级肝素对脂多糖（LPS）诱导的内毒素血症和大鼠肺损伤的保护作用及其机制。大鼠静脉注射 LPS 6mg/kg。我们通过 LPS 攻击后同时静脉内给予未分级肝素（100 或 300U/kg），检测其对内毒素血症的治疗作用。通过湿/干重比评估动物肺水肿程度。通过酶联免疫吸附试验和实时定量 RT-PCR 测定包括白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）在内的炎症介质的水平。通过 Western 印迹评估核因子-κB（NF-κB）的激活。研究表明，未分级肝素治疗可减轻 LPS 诱导的急性肺损伤大鼠模型中的炎症反应，且 300U/kg 组的效果更好。未分级肝素发挥抗炎作用的机制与通过失活 NF-κB 抑制 IL-1β 和 IL-6 的产生有关。
