GPs抑制miRNA122表达及调节脂代谢酶活性降血脂作用研究  

Research on GPs Inhibition of miRNA-122 Expression and Lipid-lowering Effect Via Regulation of Lipid Metabolism Enzyme Activity

作　　者：吴柳松[1,2] 冯永怀[2] 钱民章[1] 

机构地区：[1]遵义医学院,遵义563004 [2]遵义医学院附属医院,遵义563004

出　　处：《世界科学技术-中医药现代化》2015年第8期1679-1685,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：贵州省科技厅基金项目(黔科合J字【2009】2-178号):绞股蓝总苷对人内皮细胞的保护作用及基因差异表达的影响;负责人:钱民章

摘　　要：目的:探讨绞股蓝总苷(Gypenosides,GPs)能否抑制miRNA122表达及调节脂代谢酶活性发挥降血脂作用。方法:将48只健康雄性SD大鼠随机分为正常对照(C)组、高脂模型(M)组、辛伐他汀(S)组、GPs(G)组,除C组喂食普通饲料外,其余3组大鼠均喂食高脂饲料。将GPs溶于0.3%羧甲基纤维素钠(CMC-Na)溶液中,灌胃给药。C组和M组每天灌0.3%CMC-Na(1 m L/100 g),G组每天灌GPs 160 mg·kg-1,S组每天灌辛伐他汀5 mg·kg-1,连续进行8周。最后一次给药后禁食12 h,用7%水合氯醛腹腔麻醉,取腹腔动脉血,测定血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C);称肝脏组织湿重,测定肝指数;提取肝脏总RNA,Real time-PCR测定肝脏miRNA-122的表达;另制备肝脏组织匀浆,测定肝酯酶(HL)、脂蛋白酯酶(LPL)、HMG-Co A还原酶活性;做离体胆固醇微胶粒形成实验。结果:与C组比较,M组大鼠血清TC、TG、LDL-C水平均显著升高(P<0.01),HDL-C水平则明显下降(P<0.05);与M组比较,S组、G组TC、TG、LDL-C水平均明显下降(P<0.05),HDL-C水平则明显升高(P<0.05);与M组大鼠比较,S组、G组肝指数均明显下降(P<0.05);与M组比较,S组、G组大鼠肝脏miRNA-122的表达均明显下降(P<0.05);与M组比较,S组、G组HMG-Co A还原酶活性明显降低(P<0.05),HL、LPL活性明显升高(P<0.05);GPs在一定程度上抑制肠道中胆固醇微胶粒的形成。结论:GPs可有效降低高脂血症大鼠血脂水平,减轻肝脏脂肪病变,其降脂机理与其抑制miRNA-122表达及调节脂代谢酶活性,抑制体内胆固醇微胶粒的形成有关。This study was aimed to explore whether gypenosides （GPs） can inhibit the expression of miRNA-122 and regulate the lipid metabolism enzyme activity to play a role in lipid-lowering effect. A total of 48 healthy male SD rats were randomly divided into 4 groups, which were the normal control group （C）, hyperlipidemic model group （M）, simvastatin group （S） and the GPs group （G）. All groups were fed with high-fat diets except the normal control group which was fed with normal diets. The GPs, which were dissolved in 0.3% sodium carboxymethyl cellulose （CMC-Na） solution, were given by the intragastric administration. The C group and M group were given 0.3% CMC-Na solution （1 mL/100 g） daily. The G group was given 160 mg＆#183;kg-1 of GPs daily. The S group was given 5 mg＆#183;kg-1 of simvastatin daily. The experiment was continued for 8 weeks. After the last medication, rats were fasted for 12 hours. Rats were anesthetized with chloral hydrate （7%）. Abdominal arterial blood samples were collected to detect the total cholesterol （TC）, triglyceride （TG）, high density lipoprotein cholesterol （HDL-C） and low density lipoprotein cholesterol （LDL-C）. The wet weight of liver was weighed and the liver index was measured. The liver total RNA was extracted to determine the expression of miRNA-122 by the real-time PCR. The homogenates of liver tissues were prepared for the determination of hepatic lipase （HL）, lipoprotein lipase （LPL） and HMG-CoA reductase activity. Cholesterol micelle formation experiments were implementedin vitro. The results showed that compared with the normal control group, TC, TG and LDL-C levels of the model group were significantly increased （P〈 0.01）, while the HDL-C levels in each group were obviously decreased （P〈 0.05）. Compared with the model group, TC, TG and LDL-C levels of the S group and G group were obviously decreased （P〈 0.05）, and the HDL-C level was obviously increased （P〈 0.05）. Compared with the model group,

关 键 词：绞股蓝总苷 高脂血症 miRNA-122 脂代谢酶 

分 类 号：R543.5[医药卫生—心血管疾病]