摘要
目的研究过氧化物酶体增殖物激活型受体α激动剂非诺贝特对氧化型低密度脂蛋白诱导的人单核细胞源树突状细胞的免疫成熟的影响。方法采用免疫磁珠法分离人外周血CD14+单核细胞,经含重组人粒细胞—巨噬细胞集落刺激因子和重组人白细胞介素4的Cellgro培养5天,使其分化为未成熟树突状细胞。人单核细胞来源的树突状细胞经非诺贝特预干预后,加入氧化型低密度脂蛋白再干预,流式细胞术检测树突状细胞表型(CD1a、CD40、CD86和HLA-DR),FITC-右旋糖苷检测树突状细胞吞噬功能,酶联免疫吸附法检测细胞培养上清细胞因子(白细胞介素12、白细胞介素10和肿瘤坏死因子α)浓度。结果与氧化型低密度脂蛋白组比较,非诺贝特组CD1a、CD40、CD86和HLA-DR分别为46.50%±11.39%比68.80%±5.89%(P<0.05)、56.76%±11.16%比72.97%±10.38%(P<0.05)、65.74%±9.94%比79.82%±22.07%(P>0.05)和60.72%±11.85%比83.24%±6.60%(P<0.05);非诺贝特部分抑制氧化型低密度脂蛋白减弱树突状细胞吞噬功能(83.12%±3.10%比57.78%±23.28%,P<0.05)。与氧化型低密度脂蛋白组比较,非诺贝特组白细胞介素12、肿瘤坏死因子α和白细胞介素10分别为64.9±18.5 ng/L比106.7±20.7 ng/L(P<0.05)、26.0±8.8 ng/L比50.3±9.9 ng/L(P<0.05)和33.4±13.4 ng/L比66.1±2.6 ng/L(P<0.05)。结论过氧化物酶体增殖物激活型受体α激动剂非诺贝特可以部分阻断氧化型低密度脂蛋白诱导的树突状细胞的免疫成熟,这可能是它抗动脉粥样硬化的一个重要机制。
Aim To investigate the effect of peroxisome proliferator-activated receptors α（PPARα）agonist fenofibrate on the immune maturation of monocyte-derived dendritic cell （ DC ） induced by oxidized low-deusity lipoprotein （ ox-LDL ）. Methods Monecytes were purified （over 98% ） using Anti-CD14 microbeads. After cultured with DC Cellgro medium containing recombinated human granulocyte-macrophage colony stimulating factor （rhGM-CSF） （ 100 μg/L） and recombinated human intedeukin-4 （ rhIL-4 ） （20 μg/L） for 5 days, monocytes were derived into immature DC. Human monocyte-derived DC were incubated with fenofibrate （ 100 μmol/L） for 24 hours, and subsequently stimulated with ox-LDL （50 mg/L）for another 48 hours. The immunophenotypic expressions （CD1α, CD40, CD86, and HLA-DR） were analyzed by FACS and endecytosis function by FITC- dextran, and the cytokines secretions of culture supernatants （IL-12, IL-10, TNF-α） were measured with enzyme-linked immunosorbent assay （ELISA）. Results Fenofibrate reduced ox-LDL induced immunophenotypic expressions of DC （ CD1α： 68. 80% ±5.89% vs 46.50% ± 11.39%, P〈0.05; CD40： 72.97%±10.38% vs 56.76% ± 11.16%, P〈0.05; CD86： 79. 82%±22.07% vs65.74%±;9.94%, P〉0.05; HLA-DR： 83.24%±6.60%vs60.72%±11.85%, P〈0.05）. Ox- LDL inhibited the endocytosis of DC, which was partly prevented by fenofibrate （83.12% ± 3.10% vs 57.78%±23.28%, P 〈 0.05） ; fenofibrate attenuated ox-LDL induced cytokine secretions of DC （IL-12：106.7 ± 20.7 ng/L vs 64.9 ± 18.5 ng/L, P 〈0.05; TNFα： 50.3±9.9 ng/L vs 26.0±8.8 ng/L, P〈0.05; IL-10：66.1±2.6 ng/L vs 33.4± 13.4 ng/L, P 〈0.05）. Conclusion PPARaagonist fenofibrate partly inhibits ox-LDL induced immune maturation of DC, through which it may play an anti-atherosclerosis effect.
出处
《中国动脉硬化杂志》
CAS
CSCD
2006年第6期475-478,共4页
Chinese Journal of Arteriosclerosis
基金
国家重点基础研究发展规划资助项目(G2000056903)
上海市科委资助项目(02JC14026)
