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三磷酸腺苷结合盒转运体A1(ABCA1)是体内胆固醇逆向转运的关键环节.对氧磷是广泛使用的有机磷农药的活性代谢产物.研究发现,对氧磷能增加巨噬细胞中胆固醇的堆积,但具体机制还不清楚.以RAW264.7巨噬细胞源性泡沫细胞为研究对象,观察对氧磷对RAW264.7巨噬细胞源性泡沫细胞ABCA1表达和胆固醇流出的影响并探讨其机制.结果显示,对氧磷以时间和剂量依赖的方式增加RAW264.7巨噬细胞源性泡沫细胞中总胆固醇、游离胆固醇和胆固醇酯水平,降低ABCA1表达和胆固醇流出,同时对氧磷降低细胞中环磷酸腺苷(cAMP)的水平及腺苷酸环化酶(AC)的活性和增加磷酸二酯酶(PDE)的活性,而cAMP的类似物双丁酰环腺苷酸(dBcAMP)能够阻断对氧磷降低ABCA1表达和部分阻断对氧磷降低胆固醇流出,对氧磷导致的cAMP水平的降低也可被AC激动剂福斯高林(Forskolin)和PDE抑制剂3-异丁基-1-甲基黄嘌呤(IBMX)所阻断.以上结果表明,对氧磷通过cAMP信号通路下调RAW264.7巨噬细胞源性泡沫细胞ABCA1的表达,降低细胞内胆固醇流出和增加细胞内胆固醇堆积.
ATP-binding cassette transporter A1 (ABCA1) is a key link in the reverse cholesterol transport in vivo and paraoxon is the most widely used active metabolite of organophosphorus pesticides. Studies have found that paraoxon increases the accumulation of cholesterol in macrophages, The mechanism of RAW264.7 macrophage-derived foam cells was studied, and the effect of oxygen and phosphorus on ABCA1 expression and cholesterol efflux in RAW264.7 macrophage-derived foam cells was observed and the mechanism was discussed. , Oxygen and phosphorus in a time-and dose-dependent manner increased RAW264.7 macrophage-derived foam cells in total cholesterol, free cholesterol and cholesterol ester levels, reduce ABCA1 expression and cholesterol efflux, while oxygen and phosphorus reduction in cells cAMP (cAMP) and adenylyl cyclase (AC) activity and increase phosphodiesterase (PDE) activity, while the analog of cAMP, dibutyryl cyclic adenosine monophosphate (dBcAMP), blocks the reduction of paraoxon and phosphorus in ABCA1 Overexpression and partial blocking of paraoxon decreased cholesterol efflux, and the reduction of cAMP levels by paraoxon was also suppressed by the AC agonist Forskolin and the PDE inhibitor 3-isobutyl-1-methylxanthine ( IBMX) .The results showed that paraoxon down-regulated the expression of ABCA1 in RAW264.7 macrophage-derived foam cells through cAMP signaling pathway, decreased intracellular cholesterol efflux and increased intracellular cholesterol accumulation.