【摘要】：目的觀察親環(huán)素A(CypA)對THP-1源性泡沫細(xì)胞三磷酸腺苷結(jié)合盒轉(zhuǎn)運(yùn)體A1(ABCA1)表達(dá)和膽固醇流出的影響及機(jī)制。方法 160 nmol/L佛波酯誘導(dǎo)人THP-1單核細(xì)胞分化為巨噬細(xì)胞,與50 mg/L氧化型低密度脂蛋白(ox-LDL)共孵育,使其荷脂形成泡沫細(xì)胞,常規(guī)體外培養(yǎng)細(xì)胞;實(shí)驗(yàn)分為對照組和Cyp A處理組;液體閃爍計(jì)數(shù)儀檢測細(xì)胞膽固醇流出水平,高效液相色譜檢測細(xì)胞內(nèi)脂質(zhì)成分,實(shí)時(shí)熒光定量PCR和Western blot檢測ABCA1表達(dá),Western blot檢測核因子κB(NF-κB)核轉(zhuǎn)位水平;NF-κB抑制劑小白菊內(nèi)酯抑制NF-κB活化;脂質(zhì)體2000轉(zhuǎn)染CD147 siRNA至THP-1源性泡沫細(xì)胞。結(jié)果 CypA顯著抑制THP-1源性泡沫細(xì)胞膽固醇流出,促進(jìn)NF-κB核轉(zhuǎn)位,下調(diào)ABCA1表達(dá);NF-κB抑制劑小白菊內(nèi)酯拮抗CypA對ABCA1表達(dá)及膽固醇流出的抑制作用;用siRNA干擾CD147后,顯著抑制Cyp A誘導(dǎo)的NF-κB核轉(zhuǎn)位,上調(diào)ABCA1表達(dá),促進(jìn)膽固醇流出。結(jié)論 CypA可能通過CD147激活NF-κB,下調(diào)ABCA1表達(dá),抑制THP-1源性泡沫細(xì)胞膽固醇流出。
[Abstract]:Aim to investigate the effect and mechanism of cyclophile A (CypA) on the expression of adenosine triphosphate binding cassette transporter A1 (ABCA1) and cholesterol efflux in THP-1 foam cells. Methods Human THP-1 monocytes were induced to differentiate into macrophages at 160 nmol/L, and incubated with 50 mg/L oxidized low density lipoprotein (ox-LDL) to form foam cells, which were cultured in vitro, and were divided into two groups: control group and Cyp A treatment group. Liquid scintillation counter was used to detect cholesterol efflux, and high performance liquid chromatography (HPLC) was used to detect lipid components in cells. Real-time fluorescence quantitative PCR and Western blot were used to detect, Western blot expression of nuclear factor 魏 B (NF- 魏 B) nuclear translocation, NF- 魏 B inhibitor chrysanthemum lactone inhibited NF- 魏 B activation, and liposome 2000 was transfected into THP-1 derived foam cells. Results CypA significantly inhibited cholesterol efflux of THP-1 derived foam cells, promoted nuclear translocation of NF- 魏 B and down-regulated ABCA1 expression, and NF- 魏 B inhibitor leucolactone antagonized the inhibition of CypA on ABCA1 expression and cholesterol efflux. SiRNA interfered with CD147. The nuclear translocation of NF- 魏 B induced by Cyp A was significantly inhibited, the expression of ABCA1 was upregulated, and cholesterol efflux was promoted. Conclusion CypA may activate NF- 魏 B through CD147, down-regulate ABCA1 expression and inhibit cholesterol efflux of THP-1 derived foam cells.
【作者單位】： 邵陽學(xué)院醫(yī)學(xué)院病理生理學(xué)教研室;南華大學(xué)心血管疾病研究所動脈硬化學(xué)湖南省重點(diǎn)實(shí)驗(yàn)室南華大學(xué)醫(yī)學(xué)研究中心分子靶標(biāo)湖南省協(xié)同創(chuàng)新中心;
【基金】：國家自然科學(xué)基金項(xiàng)目(81570408、81370377和81470569) 南華大學(xué)研究生創(chuàng)新課題(2016XCX04)
【分類號】：R543.5

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