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 mL/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-CoA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-CoA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·kg-1 of GPs daily. The S group was given 5 mg·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 implemented in 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, the liver indexes of the S group and G group were obviously decreased (P < 0.05). Compared with the hyperlipidemia model group, the expressions of miRNA-122 of the S group and G group were significantly reduced (P < 0.05). Compared with the hyperlipidemia model group, the activity of HMG-CoA reductase was obviously reduced in the S group and G group (P < 0.05), but the HL and LPL activities were obviously increased (P < 0.05). GPs can inhibit the formation of cholesterol micelles to some extent. It was concluded that GPs can effectively reduce the blood lipid level in hyperlipidemic rats, in order to relieve the hepatic fatty lesions. Its lipid-lowering mechanism was related to its inhibition of miRNA-122 expression and regulation of lipid metabolism enzyme activity, as well as the inhibition on the formation of cholesterol micelles.

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。