田蓟苷对高脂饮食ApoE^(⁃/⁃)小鼠抗动脉粥样硬化活性及作用机制

Anti⁃atherosclerotic activity and mechanism of tilianin in ApoE^(⁃/⁃) mice on high⁃fat diet

目的探讨田蓟苷对高脂饮食ApoE^(⁃/⁃)小鼠抗动脉粥样硬化活性及作用机制研究。方法将ApoE^(⁃/⁃)小鼠60只随机分为普通饮食组,高脂饮食组,田蓟苷低、中、高剂量组(40、120、200 mg/kg)和阿托伐他汀给药组(15 mg/kg),1次/d,连续给药12周后,收集小鼠血清,检测其中TC(总胆固醇)、TG(甘油三酯)、HDL⁃C(高密度脂蛋白胆固醇)、LDL⁃C(低密度脂蛋白胆固醇)、ALT(谷丙转氨酶)、AST(谷草转氨酶)、TBA(总胆汁酸)和FBG(空腹血糖)水平。通过油红O染色对各组小鼠主动脉进行染色,并计算主动脉斑块面积占总血管面积之比。采用Western blot检测各组小鼠肝脏组织中PI3K(磷脂酰肌醇3⁃激酶)、p⁃PI3K、AKT(蛋白激酶B)、p⁃AKT、SREBP⁃2(固醇调节元件结合蛋白2)、LDLR(低密度脂蛋白受体)蛋白表达。结果与普通饮食组比较,高脂饮食组ApoE^(⁃/⁃)小鼠血清中TC、TG、LDL⁃C和FBG水平均升高,而HDL⁃C和TBA水平降低,差异具有统计学意义(P<0.05,P<0.01)。与高脂饮食组比较,田蓟苷高剂量组和阿托伐他汀组ApoE^(⁃/⁃)小鼠血清TC水平降低,田蓟苷高剂量组血清TG水平降低,田蓟苷低、中、高剂量组和阿托伐他汀组血清LDL⁃C水平均降低、主动脉斑块的沉积减少,田蓟苷高剂量组和阿托伐他汀给药组小鼠肝脏组织中p⁃PI3K、p⁃AKT、SREBP⁃2和LDLR蛋白表达升高,差异具有统计学意义(P<0.05,P<0.01)。结论田蓟苷可降低高脂饮食ApoE^(⁃/⁃)小鼠血脂代谢水平,减少主动脉斑块沉积,可能与调节肝脏中SREBP⁃2和LDLR蛋白表达有关,从而发挥抗动脉粥样硬化的作用。

AIM To investigate the anti⁃atherosclerotic activity and mechanism of tilianin in ApoE^(⁃/⁃) mice on high⁃fat diet.METHODS Sixty ApoE^(⁃/⁃) mice were randomly divided into normal diet group,high⁃fat diet group,experimental groups for co⁃administration of high⁃fat diet and low⁃dose,medium⁃dose and high⁃dose tilianin(40,120,200 mg/kg),and positive group for administration of high⁃fat diet and atorvastatin(15 mg/kg).After 12⁃week corresponding consecutive daily administration,the mice had their serum collected for detection of levels of TC,TG,HDL⁃C,LDL⁃C,ALT,AST,TBA and FBG;their aorta treated by oil red O staining for the determination of the ratio of the aortic plaque area to the total vascular area;their hepatic protein expressions of PI3K,p⁃PI3K,AKT,p⁃AKT,SREBP⁃2,LDLR were detected by Western⁃blot.RESULTS Compared with the normal diet group,the high⁃fat diet group demonstrated statistically significant increase in serum levels of TC,TG,LDL⁃C and FBG,and decrease in levels of HDL⁃C and TBA(P<0.05,P<0.01).We observed lower serum TC level,statistically significant increase in hepatic protein expressions of p⁃PI3K,p⁃AKT,SREBP⁃2 and LDLR(P<0.05,P<0.01)in groups intervened with high⁃dose tilianin and atorvastatin;lower TG level in high⁃dose tilianin group;lower serum LDL⁃C level,and reduced deposition of aortic plaque in all tilianin groups and atorvastatin group,in contrast to the result of the high⁃fat diet group.CONCLUSION Tilianin displays its role of regulator in hepatic SREBP⁃2 and LDLR protein expression as a mechanism contributing to the anti⁃atherosclerotic property in reducing level of blood lipid and aortic plaque deposition of ApoE^(⁃/⁃) mice on high⁃fat diet.