软脂酸、油酸和极低密度脂蛋白对巨噬细胞内毒素敏感性的影响

Effects of palmitic acid,oleic acid and VLDL on the sensitivity to endotoxin of macrophages

目的观察软脂酸、油酸和极低密度脂蛋白(VLDL)对巨噬细胞内毒素敏感性的影响。方法以小鼠巨噬细胞株RAW264.7为研究对象,分别以4种不同浓度软脂酸、油酸和VLDL干预后,用100ng/ml内毒素刺激细胞株,放射免疫法测定不同时点上清液TNFα水平;免疫细胞法观察0.125mmol/L软脂酸和油酸,7.5mmol/LVLDL对该细胞NFκB活性的影响。结果软脂酸、油酸和VLDL干预24h可使100ng/ml内毒素刺激后RAW264.7细胞生成的TNFα水平不同程度的增高,并且与3种脂质的浓度呈一定依赖性。软脂酸、油酸和VLDL干预24h还可使基础状态下RAW264.7细胞核NFκB阳性率显著增加。结论软脂酸、油酸、VLDL均能不同程度地增强巨噬细胞内毒素敏感性,此现象可能与这些脂质可诱导巨噬细胞NFκB活化有关。

Objective To investigate the effects of palmitic acid, oleic acid and very low density lipoprotein （VLDL） on the sensitivity to endotoxin of macrophages. Methods After incubated with various concentrations of palmitic acid, oleic acid or VLDL, the RAW264.7 macrophages （murine macrophage cell line） were stimulated by 100 ng/ml endotoxin, and the TNFα levels in culture medium were measured by radioimmunoassay. The effects of 0. 125 mmol/L palmitic acid, 0. 125 mmol/L oleic acid and 7.5 mmol/L VLDL on the activity of NFκB of RAW264.7 macrophages were observed by immunohistochemistry. Results Incubated by palmitic acid, oleic acid or VLDL for 24 hours, TNFa production of RAW264.7 macrophages after stimulation by 100 ng/ml endotoxin was increased and was dependent on the lipid concentrations. Exposure to palmitic acid, oleic acid or VLDL for 24 hours significantly increased the rates of positive stain of NFκB of RAW264.7 macrophages （control 5.8% ±3.4%, palmitic acid 52.7%±10.5%＊＊, oleic acid 25.2%±8.3%＊＊, VLDL 17.3%±8.7%＊,＊＊ P 〈0.01 vs control, ＊P 〈0.05 vs control） . Conclusion Palmitic acid, oleic acid and VLDL might increased the sensitivity to endotoxin of macrophages which was related to the activation of NFκB of macrophages.