[关键词]
[摘要]
目的 探讨香青兰Dracocephalum moldovica总黄酮对小鼠腹腔巨噬细胞源性泡沫细胞形成的影响及其可能机制.方法 以氧化低密度脂蛋白(Ox-LDL)诱导小鼠腹腔巨噬细胞建立泡沫细胞的模型,并以不同质量浓度的香青兰总黄酮进行干预.分别采用油红O染色观察泡沫细胞,荧光分光光度法检测细胞内胆固醇酯的量,荧光定量PCR法检测细胞内酰基辅酶A-胆固醇酰基转移酶1(ACAT-1)mRNA的表达水平,流式细胞术检测细胞表面清道夫受体A(SR-A)的表达水平.结果 香青兰总黄酮能显著抑制Ox-LDL诱导的泡沫细胞的形成、细胞内胆固醇酯的积聚、细胞中ACAT-1 mRNA及细胞表面SR-A分子的表达水平,且呈一定的剂量依赖性.结论 香青兰总黄酮通过抑制巨噬细胞源性泡沫细胞的形成,可能是其治疗动脉粥样硬化的药效机制之一.
[Key word]
[Abstract]
Objective To study the effects of total flavonoids from Dracocephalum moldovica on the formation of mouse peritoneal macrophage-derived foam cells and their possible mechanisms. Methods The mouse peritoneal macrophages were induced with oxidized low density lipoprotein (Ox-LDL) to establish foam cell model, and were intervened with different concentration of total flavonoids from D. moldovica. The foam cells were observed by oil red O staining and the contents of cholesterol ester in cells were detected by fluorescence spectrophotometric method. The expression levels of acyl-coenzyme A, cholesterol acyltransferase-1 (ACAT-1) mRNA in cells and scavenger receptor A (SR-A) on cells were determined using real-time quantitative PCR (RT-qPCR) and flow cytometry, respectively. Results The Ox-LDL-induced formation of foam cells, accumulation of cholesterol ester in cells, and the expression levels of ACAT-1 mRNA in cells and SR-A on cells were significantly inhibited by total flavonoids from D. moldovica, which showed a tendency toward a dose-dependent manner. Conclusion These data suggest that total flavonoids from D. moldovica could inhibit the formation of macrophage-derived foam cells, which is probably one of the underlying mechanisms of the total flavonoids for clinical treatment of atherosclerosis.
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[基金项目]
国家科技重大专项重大新药创制项目(2012ZX09102201-009)