附子多糖预防高胆固醇血症的作用及其对肝脏CYP7α-1表达的影响

Effects of Aconiti tuber polysaccharides on hypercholesterolemia and hepatic cholesterol 7α-hydroxylase expression in rats

目的:探讨附子多糖(FPS)预防高胆固醇血症的作用及其对肝脏胆固醇7α-羟化酶(CYP7α-1)表达的影响。方法:SPF级雄性Wistar大鼠50只,体重100 g,随机分为正常组(control)、高胆固醇组(HC)和HC+附子多糖(HC+FPS)低、中、高3个剂量组,每组10只,分别给予正常、高胆固醇及高胆固醇加附子多糖(224、448和896mg.kg-1.d-1)饮食,持续2周,检测各组的血脂水平;观察control组、HC组和HC+FPS(224 mg.kg-1.d-1)组大鼠的体重、进食量和粪便量的变化,实验结束后取3组大鼠的肝脏行HE染色;并检测3组大鼠肝脏羟甲基戊二酰辅酶A(HMG-CoA)还原酶mRNA水平、CYP7α-1 mRNA和蛋白水平以及粪便总胆汁酸含量等方面的改变。结果:附子多糖能显著抑制高胆固醇血症大鼠血清中总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)的水平(P<0.05);HC+FPS组大鼠肝细胞脂肪变性较HC组轻微;real-time PCR和Western blotting结果显示附子多糖能显著上调高胆固醇大鼠肝脏CYP7α-1 mRNA水平和蛋白表达并明显降低HMG-CoA还原酶的mRNA水平(P<0.01);HC组大鼠粪便中胆汁酸的含量增多而HC+FPS组进一步增加(P<0.05)。结论:附子多糖具有明显的降血胆固醇作用,其机制与上调CYP7α-1 mRNA及蛋白水平和下调大鼠肝脏HMG-CoA还原酶mRNA水平有关。

AIM： To investigate the effects of polysaccharides isolated from Aconiti tuber（Fuzi polysaccharides,FPS） on the prevention of hypercholesterolemia induced by high-cholesterol diet and the expression of hepatic cholesterol 7α-hydroxylase（cytochrome P450 7α-1,CYP7α-1） in rats.METHODS： Fifty male Wistar rats were randomly divided into 3 groups.The rats were fed with normal diet（control group）,high-cholesterol diet（HC group） or high-cholesterol diet plus FPS（224,448 or 896 mg·kg-1·d-1,FPS group） for 2 weeks.The serum lipid level,body weight,food-intake and fecal amount were measured at week 2.The pathological changes of the liver were observed with HE staining.The mRNA expression of hydroxy methylglutaryl coenzyme A（HMG-CoA） reductase and CYP7α-1,the protein level of CYP7α-1,and fecal bile acid were also detected at week 2.RESULTS： FPS significantly inhibited high-cholesterol diet-induced elevation of serum total cholesterol（TC） and low-density lipoprotein cholesterol（LDL-C）（P0.05）.HE staining showed that FPS attenuated fatty degeneration in liver.Real-time PCR analysis showed that FPS significantly up-regulated the mRNA expression of CYP7α-1,but down-regulated the mRNA expression of HMG-CoA reductase（P0.01）.The protein level of CYP7α-1 was higher in FPS group than that in HC group（P0.01）.The level of fecal bile acid in HC-treated rats was higher than that in the control rats,and FPS stimulated the excretion of fecal bile acid（P0.05）.CONCLUSION： FPS significantly reduces serum cholesterol levels,which is associated with the up-regulation of hepatic CYP7α-1 expression and down-regulation of hepatic HMG-CoA reductase expression.