【摘要】 目的探讨瑞舒伐他汀经过氧化物酶体增殖物激活受体γ-肝脏X受体α（PPARγ-LXRα）信号通路抑制THP-1巨噬细胞脂质蓄积的机制。方法 2018年12月—2019年3月于海口市人民医院/中南大学湘雅医学院附属海口医院中心实验室进行实验。设立THP-1巨噬细胞对照组（0 mmol/L ox-LDL）、ox-LDL组（100 mmol/L ox-LDL）及瑞舒伐他汀低、中、高剂量组（100 mmol/L ox-LDL+10.0μg/ml瑞舒伐他汀、100 mmol/L ox-LDL+100.0μg/ml瑞舒伐他汀、100 mmol/L ox-LDL+1 000.0μg/ml瑞舒伐他汀）,各组细胞置于CO₂培养箱,培养72 h。培养结束后,MTT法测定THP-1巨噬细胞活力,流式细胞仪测定THP-1巨噬细胞凋亡水平,贝克曼AU-480型生化仪测定THP-1巨噬细胞TC、FC、CE水平,RT-PCR法及Western-blot法测定THP-1巨噬细胞PPARγ、LXRα基因和蛋白水平。结果与对照组比较,ox-LDL组巨噬细胞OD值、存活率、TC、FC、CE水平明显升高（P<0.05）,凋亡率、PPARγ、LXRαmRNA和蛋白水平明显降低（P<0.05）,与ox-LDL组比较,瑞舒伐他汀各剂量组OD值、存活率、TC、FC、CE明显降低（F=13.254、24.145、121.321、259.658、368.487,P均=0.000）,凋亡率、PPARγ、LXRαmRNA和蛋白水平明显升高（F=19.632、16.145、18.547、21.214、23.148,P均=0.000）,且随着瑞舒伐他汀剂量的增加,瑞舒伐他汀各剂量组OD值、存活率、TC、FC、CE逐渐降低,凋亡率、PPARγ、LXRαmRNA和蛋白水平逐渐升高,差异有统计学意义（P<0.01）。结论瑞舒伐他汀能促进THP-1巨噬细胞胆固醇流出,减少THP-1泡沫细胞中的脂质积累;其机制与瑞舒伐他汀促进PPARγ、LXRαmRNA和蛋白表达,进而激活PPARγ/LXRα途径有关。更多还原

【Abstract】 Objective To investigate the inhibition of lipid accumulation in THP-1 macrophages by rosuvastatin via PPARγ-LXRα signaling pathway. Methods Experiments were performed at the Department of Molecular Biology of our hospital from December 2018 to March 2019. THP-1 macrophage control group（0 mmol/L ox-LDL）, ox-LDL group（100 mmol/L ox-LDL）, rosuvastatin low, medium and high dose group（100 mmol/L ox-LDL+10.0 μg/ml rosuvastatin, 100 mmol/L ox-LDL+100.0μg/ml rosuvastatin, 100 mmol/L-ox-LDL+1 000.0 μg/ml rosuvastatin, respectively） were established. The cells were placed in a CO₂ incubator（37℃, 5% CO₂, 2% O₂, 93% N₂）. The above groups were cultured for 72 hours with 6 parallel samples per hole. After culture, the activity of THP-1 macrophages was measured by MTT, the apoptotic level of THP-1 macrophages was measured by flow cytometry, the levels of TC, FC, and CE of THP-1 macrophages were measured by Beckman AU-480, and the levels of PPARγ, LXRα gene, and protein of THP-1 macrophages were determined by RT-PCR and Western blot. Results Compared with a relative, the OD value, survival rate, TC, FC, and CE levels of the ox-LDL group were significantly increased（F/P=15.654/0.000, F/P=25.147/0.000, F/P=18.654/0.000, F/P=26.654/0.000, F/P=35.147/0.000）, distinguished Rate, PPARγ, LXRα mRNA and protein levels were significantly reduced（F/P=19.654/0.000, F/P=26.541/0.000, F/P=19.854/0.000, F/P=26.541/0.000）. Compared with the ox-LDL group, the OD values of each rosuvastatin dose group survived. Rate, TC, FC, CE significantly decreased（F/P=15.417/0.000, F/P=26.241/0.000, F/P=19.547/0.000, F/P=23.014/0.000, F/P=18.543/0.000）, increased rates, PPARγ, LXRα mRNA and protein levels were significantly increased（F/P=26.547/0.000, F/P=35.654/0.000, F/P=42.216/0.000, F/P=38.471/0.000, F/P=34.547/0.000） and converted into an increase in rosuvastatin dose, OD value, survival rate, TC, FC, CE gradually decreased, the gradual rate, PPARγ, LXRα mRNA and protein levels gradually increased, the differences were statistically significant（F/P=29.547/0.000, F/P=36.417/0.000, F/P=52.146/0.000, F/P=32.214/0.000, F/P=42.214/0.000, F/P=46.471/0.000, F/P=49.547/0.000, F/P=29.654/0.000, F/P=56.147/0.000）. Conclusion Rosuvastatin can promote cholesterol efflux in THP-1 macrophages and reduce lipid accumulation in THP-1 foam cells. The mechanism is related to rosuvastatin promoting PPARγ, LXRα mRNA and protein expression, and then activating PPARγ/LXRα pathway.更多还原