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绞股蓝总苷颗粒改善高脂血症C57BL/6J小鼠脂代谢的研究
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引用本文:张瑶丹,姜新宇,操兰洁,王杰,蒋翠花,赵梦鸽,张健,殷志琦.绞股蓝总苷颗粒改善高脂血症C57BL/6J小鼠脂代谢的研究[J].中国药科大学学报,2019,50(6):713-720.
Cite:ZHANG Yaodan,JIANG Xinyu,CAO Lanjie,WANG Jie,JIANG Cuihua,ZHAO Mengge,ZHANG Jian,YIN Zhiqi.Gypenoside granules improved lipid metabolism in C57BL/6J mice with hyperlipidemia[J].J China Pharm Univ,2019,50(6):713-720.
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作者单位
张瑶丹 万邦德制药集团杭州医药技术有限公司 
姜新宇 湖南华宝通制药有限公司 
操兰洁 中国药科大学中药学院中药制剂系&天然药物活性组分与药效国家重点实验室 
王杰 中国药科大学中药学院中药制剂系&天然药物活性组分与药效国家重点实验室 
蒋翠花 江苏省中医药研究院转化医学实验室 
赵梦鸽 中国药科大学中药学院中药制剂系&天然药物活性组分与药效国家重点实验室 
张健 江苏省中医药研究院转化医学实验室 
殷志琦 中国药科大学中药学院中药制剂系&天然药物活性组分与药效国家重点实验室 
基金项目:江苏省自然科学基金资助项目(No.BK20161460);江苏高校优势学科建设工程资助项目(PAPD)
中文摘要: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。
中文关键词:绞股蓝  绞股蓝总苷颗粒  联合用药  高脂血症  胆固醇逆转运
 
Gypenoside granules improved lipid metabolism in C57BL/6J mice with hyperlipidemia
Abstract:To investigate the hypolipidemic effects of gypenosides granules and its combination with lipitor, a model of hyperlipidaemia C57BL/6J 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(CYP7A1)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, CYP7A1 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.
keywords:Gynostemma pentaphyllum  gypenosides granules  drug combination  hyperlipidemia  reverse cholesterol transport
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