依折麦布对饮食性高胆固醇血症大鼠胆固醇吸收及代谢相关靶点的调节作用

Regulation effect of Ezetimibe on the cholesterol absorption and metabolism in diet-induced hypercholesterolemia rats

目的探讨依折麦布对饮食性高胆固醇血症大鼠胆固醇吸收及代谢相关靶点的调节作用。方法雄性SD大鼠,正常组喂食普通饲料,其余组喂食高脂饲料,复制饮食性高胆固醇血症大鼠模型。依折麦布组除喂食高脂饲料外,每天灌胃给药,连续给药4周,测定大鼠血清、粪便、肝脏的总胆固醇,并测定大鼠肝脏CYP7A1、LXRα、小肠NPC1L1 mRNA和蛋白的表达水平。结果与正常组比较,模型组大鼠血清、粪便总胆固醇含量均显著上升(P<0.01),肝脏总胆固醇含量上升(P<0.05)。与模型组比较,依折麦布组大鼠血清、肝脏总胆固醇含量均显著下降(P<0.01),粪便总胆固醇含量显著上升(P<0.01)。依折麦布组大鼠肝脏CYP7A1、LXRα、小肠NPC1L1 mRNA和蛋白的表达与模型组、正常组比较均显著下降(P<0.01)。结论依折麦布能降低饮食性高胆固醇血症大鼠血清和肝脏总胆固醇含量,增加粪便总胆固醇排出,并能抑制肝脏CYP7A1及小肠NPC1L1的表达,其抑制CYP7A1表达可能与下调LXRα有关。

Objective To study the regulation effect of Ezetimibe on the cholesterol absorption and metabolism in diet-induced hypercholesterolemia rats. Methods Health Sprague Dawley （SD） rats were divided into the control group, the model group and the Ezetimibe group. Except the control group, other two groups were fed with high fat diet to establish hypercholesterolemia. Ezetimibe was intragastrically administered to the Ezetimibe group for four weeks. Total cholesterol levels of serum, feces and liver, mRNA and protein expressions of liver CYPTA1, LXRα and intestinal NPC iLl were measured. Results Compared to the control group, the total cholesterol levels of serum, feces and liver in the model group were significantly increased （P〈0.05）. Compared to the model group,the total cholesterol levels of serum and liver in the Ezetimibe group were significantly decreased （P〈0.01）, but the total cholesterol levels of feces were significantly increased （P〈0.01）. mRNA and protein expressions of liver CYPTA1, LXRα and intestinal NPC1L1 were decreased in the Ezetimibe group when compared with both the control and model groups （P〈0.01）. Conclusion Ezetimibe can decrease the total cholesterol levels of serum and liver in diet-induced hypereholesterolemia rats and enhance the excretion of feces total cholesterol. Ezetimibe inhibits the expression of liver CYPTA1 ,which may be related to down-regulation of LXRα expression.