二甲双胍介导胆固醇逆转运抑制动脉粥样硬化

Metformin mediated reverse cholesterol transport to inhibit atherosclerosis

目的探讨二甲双胍通过对胆固醇逆转运抑制ApoE^-/-小鼠动脉粥样硬化的分子机制。方法18只ApoE^-/-小鼠随机分为三组,对照组、模型组和二甲双胍组,每周监测体质量变化。取血检测血清血脂水平;小动物超声检测腹主动脉管壁厚度;HE和油红O染色评价肝脏脂肪病变程度;Western blot检测肝脏胆固醇逆转运相关蛋白LXRɑ、ABCA1的表达。结果与对照组比,模型组体质量、血清TC、TG、LDL升高,HDL降低(P<0.05),腹主动脉管壁增厚(P<0.05),肝脏脂肪沉积加重及LXRɑ、ABCA1的表达降低。二甲双胍组体质量、血清TC、TG、LDL降低,HDL升高(P<0.05),肝脏脂肪沉积及腹主动脉管壁厚度显著减轻(P<0.05),LXRɑ、ABCA1表达显著增高(P<0.05)。结论二甲双胍通过上调肝脏胆固醇逆向转运相关蛋白LXRɑ和ABCA1的表达,增强肝脏胆固醇逆转运能力,调节血脂代谢、减轻肝脏脂质沉积,从而延缓动脉粥样硬化的进展。

Aim To investigate the molecular mecha-nism of metformin inhibiting atherosclerosis in ApoE^-/-mice by reverse cholesterol transport.Methods Eighteen ApoE^-/-mice were randomly divided into three groups,control group,model group and metformin group,and body weight changes were monitored weekly.Blood samples were taken to measure serum lipid levels;animal ultrasound was used to measure abdominal aortic wall thickness;HE and oil red O staining were used to evaluate the degree of liver steatosis;Western blot was used to detect the expression of liver cholesterol reverse transport-related proteins LXRɑand ABCA1.Results Compared with control group,the body weight,serum TC,TG,and LDL in model group increased,HDL decreased(P<0.05),abdominal aortic wall thickened(P<0.05),liver fat deposition increased,and LXRɑ,ABCA1 expression was reduced.In metformin group,body weight,serum TC,TG,LDL decreased,HDL increased(P<0.05),liver fat deposition and abdominal aortic wall thickness were significantly reduced(P<0.05),and LXRɑand ABCA1 expressions markedly increased(P<0.05).Conclusions Metformin can delay the progression of atherosclerosis by up-regulating the expression of liver cholesterol reverse transport related proteins LXRɑand ABCA1,enhancing liver reverse cholesterol transport,regulating blood lipid metabolism and reducing liver lipid deposition.