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Study on the Mechanism of Gegen Qinlian Decoction for Lowering Blood Lipids and Preventing Blood
Glucose Increase Based on Intestinal Flora
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JIANG Yingna ，ZENG Zhijun ，FU Lingyan ，SHENG Yixuan ，ZENG Guowei ，YAO Liangliang ，WANG
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Weiwei ，ZHOU Ziyan ，XU Guoliang 1，2，3 ，LIU Hongning 1，2 （1. Research Center for Differentiation and
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Development of TCM Basic Theory，Jiangxi University of TCM，Nanchang 330004，China；2. Jiangxi Key
Laboratory of TCM Etiopathogenesis，Nanchang 330004，China；3. Jiangxi Key Laboratory of Pharmacology of
TCM，Nanchang 330004，China）
ABSTRACT OBJECTIVE：To study the effects of Gegen qinlian decoction （GGQLD） on blood lipid and blood glucose of
hyperlipidemia（HLP）model rats，and to explore its mechanism from the perspective of intestinal flora. METHODS：Totally 48
rats were randomly divided into blank control group（n＝8）and modeling group（n＝40）. For consecutive 5 weeks，model group
was given high-lipid diet to induce HLP model；blank control group was given routine diet. After modeling，30 modeling rats were
randomly divided into model group，simvastatin group （positive control，10 mg/kg），GGQLD high-dose，medium-dose and
low-dose groups（14.85，4.95，1.65 g/kg，by crude drug），with 6 rats in each group. Blank control group and model group were
given constant volume of normal saline intragastrically；administration groups were given relevant medicine intragastrically，once a
day，for consecutive 11 weeks. At the same time，each group was continuously given corresponding diet. After the last medication，
body mass and body length of rats were determined，and Lee’s index was calculated. Serum levels of TG，TC，HDL-C，LDL-C
and fasting blood glucose（FBG）were determined in rats. DNA of rat caecum content was extracted for 16S rRNA V3-V4 region
sequencing. The Two-part model was used to analyze the correlation between intestinal flora with lipids and blood glucose.
RESULTS：After 11 weeks of administration，compared with blank control group，the body mass，body length，Lee’s index，
serum levels of TC，TG，HDL-C and FBG of model group were increased significantly（P＜0.05 or P＜0.01），while the level of
HDL-C was decreased significantly（P＜0.05）. Compared with model group，body mass and Lee’s index and serum levels of TG，
FBG of rats in GGQLD high-dose group，and serum levels of TC，TG in GGQLD medium-dose group，as well as serum level of
TG of rats in GGQLD low-dose group was decreased significantly（P＜0.05 or P＜0.01）. Correlation analysis with intestinal flora
showed that TC and TG shared 3 operational taxonomic units（OTU），including OTU559，OTU701 and OTU135（OTU135 was
also shared with FBG），which were all positively correlated with the level of TC，TG and FBG（P＜0.01）. The three OTU were
annotated as Tyzzerella of Spirillaceae，Anaerotruncus of Verrucaceae and Peptoclostridium of Streptococcidae，respectively.
High-dose and low-dose GGQLD had a down-regulating effect on Tyzzerella and Anaerotruncus（P＜0.05 or P＜0.01），while had
up-regulating effect on Peptoclostridium（P＜0.01）. CONCLUSIONS：High-dose GGQLD（14.85 g/kg）can effectively reduce the
body mass and blood lipid of HLP model rats，and can prevent the abnormal increase of blood glucose of model rats. The
mechanism may be associated with that the reduction of intestinal flora（Tyzzerella，Anaerotruncus）content.
KEYWORDS Hyperlipidemia；Gegen qinlian decoction；Intestinal flora；Glucose-lowering；Lipid-lowering；Rats；Mechanism

高脂血症（HLP）是常见的脂质代谢性疾病，是由于 水平 ，并有较好的降血脂作用 [7-8] 。但临床上并未见以
[6]
血液总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固 葛根芩连汤作为降脂并且预防血糖升高的给药用途。
醇（LDL-C）水 平 的 升 高 和 高 密 度 脂 蛋 白 胆 固 醇 肠道菌群是机体复杂的微生物生态系统，与宿主关
[1]
（HDL-C）水平的降低所致 。HLP往往是糖代谢紊乱的 系极为密切，是宿主能量代谢的重要调节因素，肠道菌
始动因素，因此，药物干预HLP可以预防血糖升高，进而 群失调容易导致机体发生肥胖、血脂异常等代谢性疾
[2]
预防相关糖脂代谢类疾病 。有研究发现，高糖“代谢记 病 。研究表明，血糖、血脂也受肠道菌群调控的影响，
[9]
忆”与糖尿病并发症密切相关，即患者若长期处于高血 其作用机制可能与肠道菌群参与胆酸合成和代谢、调节
糖状态，即使后来血糖水平降低，仍易发生糖尿病相关 胆汁酸代谢、发酵碳水化合物最终生成短链脂肪酸有
并发症 [3-4] ，故在糖尿病前期尽早治疗，严格控制患者血 关 [10-11] 。基于此，本研究拟通过一种改良的相关性分析
糖水平，可能会降低糖尿病及其并发症的患病风险。葛 方法——Two-part模型法——进行肠道菌群操作性分类
根芩连汤出自《伤寒论》，由葛根、黄芩、黄连和炙甘草 4 单元（Operational taxonomic units，OTU）水平与血糖、血
味药材组成，经方多用于湿热下利，现临床上主要用于 脂的关联性分析，确定对血糖、血脂有影响的重要肠道
肠道湿热型糖尿病、结肠炎、动脉粥样硬化的治疗 。临 菌群的 OTU，以期从 OTU 水平探究葛根芩连汤对 HLP
[5]
床试验和药理实验都表明，葛根芩连汤能有效控制血糖 的治疗作用以及对血糖异常升高的预防作用，为其临床

·1824 · China Pharmacy 2020 Vol. 31 No. 15 中国药房 2020年第31卷第15期