绞股蓝总苷颗粒改善高脂血症C57BL/6J小鼠脂代谢的研究

Gypenoside granules improved lipid metabolism in C57BL/6J mice with hyperlipidemia

为评价绞股蓝总苷颗粒以及其与他汀联用的降血脂作用,采用高脂饲料诱导构建高脂血症C57BL/6J小鼠模型。随机分为空白组、模型组、阳性药组(Lip,10 mg/kg)、绞股蓝总苷颗粒低、中、高剂量组(L、M、H,90,120,180 mg/kg),联合组(Lip+H,180 mg/kg+10 mg/kg)。连续给药4周后检测血脂成分、血清ALT、AST及载脂蛋白B(Apo B)含量,H&E染色观察小鼠肝脏病理变化,利用RT-PCR法和Western blot法测定三磷酸腺苷结合盒转运体A1(ABCA1)、肝X受体(LXRα)、胆固醇7α-羟化酶(CYP7A1)和B族Ι型清道夫受体(SR-BΙ)等肝脏胆固醇代谢关键因子蛋白、基因表达水平。结果显示绞股蓝总苷颗粒能显著降低小鼠体重、腹部脂肪质量及血清总胆固醇(TC)、AST水平,并修复受损小鼠肝细胞;联合组能显著降低小鼠TC水平,效果优于绞股蓝总苷颗粒高剂量组和阳性药单用组。此外,绞股蓝总苷颗粒能显著升高ABCA1的蛋白水平,同时上调ABCA1、CYP7A1和SR-BΙ的基因表达。实验结果表明,绞股蓝总苷颗粒能够显著降低血脂,且与阿托伐他汀联用后降脂效果提高,并可降低血清转氨酶,初步探索其降脂机制可能是通过参与胆固醇逆转运调节TC含量。

To investigate the hypolipidemic effects of gypenosides granules and its combination with lipitor,a model of hyperlipidaemia C57 BL/6 J mice was established by high-fat diet feeding for 4 weeks.The mice were randomly divided into blank group,model group,lipitor group(10 mg/kg of lipitor),low dose group(90 mg/kg of gypenosides granules),medium dose group(120 mg/kg of gypenosides granules),high dose group(180 mg/kg of gypenosides granules) and the combination group(180 mg/kg of gypenosides granules and 10 mg/kg of lipitor).After 4 weeks of continuous administration,the contents of serum lipid indexes,serum ALT,AST and apolipoprotein B(ApoB) were measured.The liver tissues of mice were observed by H&E staining.The expression levels of key factors involved in hepatic cholesterol metabolism were observed by RT-PCR and Western blot methods,such as adenosine triphosphate combined box transporter A1(ABCA1),liver X receptor(LXRα),cholesterol 7 alpha hydroxylase(CYP7 A1) and type BΙ scavenger receptor(SR-BΙ).The results revealed that gypenosides granules significantly decreased the mice body weight,total abdominal fat area and the level of serum total cholesterol(TC).The combination group showed a more significant reduction in TC level than the other administration groups.Moreover,gypenosides granules treatment remarkably increased the protein expression of ABCA1 and up-regulated the mRNA expression of ABCA1,CYP7 A1 and SR-BI.The above results suggest that gypenosides granules can significantly reduce blood lipid contents,and the combination therapy with lipitor show better the lipid-lowering effect.Meanwhile,gypenosides granules can decrease the level of serum transaminase.Preliminary exploration suggests the lipid-lowering mechanism of gypenosides granules may be involved in cholesterol reversal to regulate the level of TC.