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ABSTRACT OBJECTIVE：To investigate the effects of gypenosides（GPs）on gene expression of major urinary proteins（Mups）
in liver tissue of hypercholesterolemia model mice. METHODS：C57BL/6J mice were divided into control（ND）group，model
（HFD）group and GPs therapy（GP）group according to body weight（BW），with 11 mice in each group. Except for ND group，
other groups were given high-lipid diet to induce hypercholesterolemia model. From the 17th week of feeding，ND group and HFD
group were given constant volume of 0.1％CMC-Na solution intragastrically；GP group were given GPs suspension（250 mg/kg）
intragastrically，once a day，for consecutive 22 weeks. BW，the levels of blood glucose（BG）and blood lipid（TC，LDL-C）were
detected in each group. Total RNA of liver tissue was extracted，and reverse transcription library was constructed and RNA-seq
sequencing was performed. The differentially expressed genes were screened by PCA，volcano map and scatter plot. RT-qPCR was
used for verification for differentially expressed genes. The correlation between the expression of differentially expressed genes and
the above pharmacodynamic indexes was analyzed by bivariate analysis. RESULTS：Compared with ND group，BW，the levels of
BG，TC and LDL-C in HFD group were increased significantly（P＜0.05）. Compared with HFD group，above indexes of GP
group were decreased significantly except for BW（P＜0.05）. PCA showed that the data of ND group and HFD group distributed in
different quadrants，and the data distribution of GP group was between above two groups. mRNA of Mup4，Mup5，Mup11，Mup15
and Mup21 in liver tissue of mice were increased significantly after treated with high-fat diet（P＜0.05）. mRNA of Mup3，Mup4，
Mup5，Mup8，Mup12 and Mup21 were decreased significantly after treated with GPs（P＜0.05）. In ND group vs. HFD group and
HFD group vs. GP group，mRNA of Mup4，Mup5 and Mup21 genes changed significantly and the trend was opposite. Results of
RT-qPCR verification showed that compared with ND group，relative mRNA expression of Mup4，Mup5 and Mup21 gene were
increased significantly in HFD group （P＜0.05）. Correlation analysis revealed that mRNA expression of Mup5 was positively
correlated with the levels of TC and BG（r＝0.727 1，0.670 6，P＜0.05），mRNA expression of Mup4 and Mup21 were positively
correlated with the level of BG（r＝0.737 8，0.721 5，P＜0.05）. CONCLUSIONS：GPs can regulate the expression of Mups genes
in liver tissue of hypercholesterolemia model mice， and reduce glucose and lipid level through regulating the mRNA
over-expression of Mup4，Mup5 and Mup21.
KEYWORDS Gypenosides；Hypercholesterolemia；Major urinary proteins；Glucose and lipid metabolism；Transcriptome；Mice

高胆固醇血症是冠状动脉粥样硬化、心肌梗死、脑 记载，其能“清火解毒、生肌收敛、降脂减肥，主要用于皮
[11]
卒中等多种高致死性心脑血管疾病的直接诱因，其特征 肤瘙痒、高血脂、肥胖病” ；《中华本草·苗药卷》记载，
[1]
主要是血液中脂质水平升高、机体脂质代谢紊乱 。脂 其能“清热解毒、益气养阴、生津、安神，用于体虚乏力、
[2]
[12]
质通过与脂质运载蛋白结合并被运输至各个器官 ，可 疲劳失津、慢性支气管炎” 。皂苷类成分是绞股蓝的
见该运载蛋白可能与高胆固醇血症的形成密切相关。 主要有效成分之一，有文献报道，绞股蓝总皂苷（Gype-
主要尿蛋白（Major urinary proteins，Mups）是一类分子 nosides，GPs）可显著降低实验动物血浆中总胆固醇
[3]
量为 18～19 kDa 的脂质运载蛋白家族 。作为载体， （TC）、低密度脂蛋白胆固醇（LDL-C）、三酰甘油（TG）水
Mups可结合并运输亲脂性小分子物质（如脂肪酸、视黄 平，并可显著升高高密度脂蛋白胆固醇（HDL-C）水平，
[4-5]
醇、类固醇和信息素等） ，并可独立于化学信号转导， 从而有效改善脂质代谢紊乱 [13-15] 。有研究表明，给予高
直接参与机体糖脂代谢的调节 。目前，有关Mups调节 脂模型大鼠 GPs（250 mg/kg）治疗 12 d 后，其血清 TC、
[6]
[16]
糖脂代谢的相关研究相对较少，尚有待深入挖掘；同时， TG水平均明显降低 。本课题组前期研究也已证实了
其编码基因 Mups 为具有高度多态性的多基因家族，由 GPs（250 mg/kg）可通过调控胆汁酸代谢通路将高脂饮
21个Mups基因和21个伪基因组成 [7-8] 。合成Mups的主 食诱导的高胆固醇血症模型小鼠血清中 TC、LDL-C 水
要部位为肝脏，当肝脏受到损伤时，Mups基因的表达将 平回调至正常状态，有效改善其脂质代谢紊乱，使小鼠
发生改变，从而导致脂质代谢异常 。有研究表明，高脂 相关症状得以缓解 [17-18] 。然而，上述脂质水平调节作用
[9]
饮食可引起部分 Mups 基因 mRNA 表达增加；给予药物 是否与 Mups 基因相关尚未见相关报道。为此，本研究
治疗后，Mups 的表达受到抑制且高脂饮食引起的相关 拟采用转录组学技术（RNA-Seq 测序技术）探讨 GPs 对
症状得以缓解 。由此可见，高脂饮食引起的高胆固醇 高胆固醇血脂模型小鼠肝组织中的21个Mups基因表达
[10]
血症可能与 Mups 基因表达密切相关，并且药物可能通 的影响，并采用实时荧光定量聚合酶链反应法（RT-qP-
过调控 Mups 基因的表达来发挥对脂质代谢的调节 CR）进行验证，为探讨绞股蓝总皂苷降糖降脂的作用机
作用。 制提供参考。
绞 股 蓝 为 葫 芦 科 植 物 绞 股 蓝 [Gynostemma pen- 1 材料
taphyllum（Thunb.）Makino]的干燥地上部分，在傣、苗、 1.1 仪器
壮族等多种民族药中均有应用。如《中药本草·傣药卷》 Multiskan GO型全波长酶标仪、Nanodrop型超微量

·1810 · China Pharmacy 2020 Vol. 31 No. 15 中国药房 2020年第31卷第15期