基于肠道菌群研究葛根芩连汤降脂并预防血糖升高的作用机制
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篇名: 基于肠道菌群研究葛根芩连汤降脂并预防血糖升高的作用机制
TITLE: Study on the Mechanism of Gegen Qinlian Decoction for Lowering Blood Lipids and Preventing Blood Glucose Increase Based on Intestinal Flora
摘要: 目的:研究葛根芩连汤对高脂血症(HLP)模型大鼠血脂、血糖的影响,并从肠道菌群角度探索其作用机制。方法:将48只大鼠随机分为空白对照组(n=8)和造模组(n=40)。造模组大鼠连续5周饲以高脂饲料以复制HLP模型,空白对照组大鼠饲以普通饲料。将造模成功的30只大鼠随机分为模型组、辛伐他汀组(阳性对照,10mg/kg)和葛根芩连汤高、中、低剂量组(14.85、4.95、1.65g/kg,以生药量计),每组6只。空白对照组和模型组大鼠灌胃等体积生理盐水,各给药组大鼠灌胃相应药物,每天给药1次,连续给药11周;给药同时,各组大鼠继续饲以相应饲料。末次给药后,测定大鼠体质量、体长并计算Lee’s指数;检测大鼠血清中三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和空腹血糖(FBG)水平。提取大鼠盲肠内容物DNA进行16SrRNAV3~V4区域测序,并应用Two-part模型进行肠道菌群与血脂、血糖的关联分析。结果:给药11周后,与空白对照组比较,模型组大鼠体质量、体长、Lee’s指数以及血清中TC、TG、HDL-C、FBG水平均显著增加或升高(P<0.05或P<0.01),HDL-C水平显著降低(P<0.05);与模型组比较,葛根芩连汤高剂量组大鼠体质量、Lee’s指数和TG、FBG水平,葛根芩连汤中剂量组大鼠血清中TC、TG水平和葛根芩连汤低剂量组大鼠血清中TG水平均显著降低(P<0.05或P<0.01)。与肠道菌群的关联分析发现,TC和TG共享3个操作性分类单元(OTU),分别为OTU559、OTU701和OTU135(其中OTU135也与FBG共享),且均与TC、TG或FBG水平呈显著正相关(P<0.01),这3个OTU分别注释到毛螺菌科Tyzzerella属、疣微菌科Anaerotruncus属和链球菌科Peptoclostridium属。高、中剂量葛根芩连汤对Tyzzerella、Anaerotruncus属微生物丰度有显著下调作用(P<0.05或P<0.01),但对Peptoclostridium属微生物丰度有显著上调作用(P<0.01)。结论:高剂量(14.85g/kg)葛根芩连汤可有效降低HLP模型大鼠的体质量和血脂水平,并可预防模型大鼠血糖的异常升高;其作用机制可能与降低肠道菌(Tyzzerella、Anaerotruncus属)的含量有关。
ABSTRACT: OBJECTIVE:To study the ef fects 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 V 3-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 OTU 559,OTU701 and OTU 135(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.
期刊: 2020年第31卷第15期
作者: 姜璎娜,曾治君,傅灵艳,盛译萱,曾国威,姚亮亮,王玮玮,周子妍,徐国良,刘红宁
AUTHORS: JIANG Yingna,ZENG Zhijun,FU Lingyan, SHENG Yixuan,ZENG Guowei,YAO Liangliang,WANG Weiwei,ZHOU Ziyan,XU Guoliang,LIU Hongning
关键字: 高脂血症;葛根芩连汤;肠道菌群;降糖;降脂;大鼠;机制
KEYWORDS: Hyperlipidemia;Gegen qinlian decoction ;Intestinal flora ;Glucose-lowering;Lipid-lowering;Rats;Mechanism
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