丹参酮ⅡA促进胆固醇逆向转运改善动脉粥样硬化

TanshinoneⅡA promotes reverse cholesterol transport to improve atherosclerosis

目的探究丹参酮ⅡA对动脉粥样硬化模型小鼠及巨噬细胞RAW264.7胆固醇逆向转运的影响及其作用机制。方法雄性LDLR-/-小鼠32只随机分为4组,给予普通饲料或高脂饲料喂养12周。对照组、模型组给予生理盐水,丹参酮ⅡA组、阿托伐他汀组给予丹参酮ⅡA溶液、阿托伐他汀溶液干预12周。RAW264.7细胞用氧化型低密度脂蛋白(ox-LDL)100 mg·L^(-1)诱导24 h,并同时给予含有丹参酮ⅡA低、中、高剂量(10、20、40μmol·L^(-1))的培养基。检测小鼠血清TC、TG、LDL-C、HDL-C值。油红O染色观察小鼠主动脉根部、RAW264.7细胞内脂质积聚。Western blot测定小鼠主动脉组织、肝组织、RAW264.7细胞ABCA1、ABCG1蛋白表达。结果与模型组比较,丹参酮ⅡA、阿托伐他汀降低小鼠血清TC、TG、LDL-C水平,升高HDL-C水平(P<0.05),减小小鼠主动脉根部斑块相对管腔面积比值,上调小鼠主动脉组织、肝组织ABCA1、ABCG1蛋白水平(P<0.05);丹参酮ⅡA减少RAW264.7细胞内的脂滴累积,ABCA1、ABCG1蛋白表达增加(P<0.05)。结论丹参酮ⅡA通过促进胆固醇逆向转运,抑制泡沫细胞形成,改善脂代谢,发挥抗动脉粥样硬化的作用。

Aim To explore the effect of tanshinoneⅡA(TanⅡA)on reverse cholesterol transport in atherosclerosis model mice and RAW264.7 cells and the underlying mechanism.Methods Thirty-two male LDLR-/-mice were randomly divided into four groups.These mice were fed with normal diet or high fat diet for 12 weeks.The control group and model group were given normal saline.TanⅡA group and atorvastatin group were given TanⅡA solution and atorvastatin solution for 12 weeks.RAW264.7 cells were induced with oxidized low-density lipoprotein(ox-LDL)100 mg·L^(-1)for 24 h,and at the same time,they were given a medium containing TanⅡA at low-,medium-and high-dose(10,20,40μmol·L^(-1)).Biochemical detection methods were used to detect the serum TC,TG,LDL-C and HDL-C values of mice.Oil red O staining was used to observe mouse aortic sinus plaque area and the formation of foam cell.Western blot was used to determine the protein expression of ABCA1 and ABCG1in mouse aortic tissue,liver tissue and RAW264.7 cells.Results Compared with the model group,TanⅡA and atorvastatin reduced the levels of serum TC,TG and LDL-C in mice,and increased the level of serum HDL-C(P<0.05),reduced the relative lumen area ratio of aortic root plaque in mice,and up-regulated the protein levels of ABCA1 and ABCG1(P<0.05).TanⅡA also reduced the accumulation of lipid droplets in RAW264.7 cells,and up-regulated the expression of ABCA1,ABCG1 protein(P<0.05).Conclusions TanⅡA exerts anti-atherosclerotic effects through promoting reverse cholesterol transport,inhibiting foam cell formation,and improving lipid metabolism.