低剂量黄连素对小鼠肠道短链脂肪酸和胆汁酸成分以及血脂的影响

Effects of low-dose berberine on composition of short chain fatty acids and bile acids in the intestinal tract and serum lipids in mice

目的研究低剂量黄连素对正常饮食小鼠肠道短链脂肪酸、胆汁酸以及血脂的影响,探讨其降血脂作用的机制。方法 40只C57BL/6小鼠被随机分为对照组和黄连素低、中、高剂量组,每组雌雄各5只。除对照组外,低、中、高剂量实验组分别以10、20、40 mg·kg-1·d-1的剂量将黄连素添加至饮水中进行干预。4周后检测体脂率、瘦体重率、血清总胆固醇(total cholesterol,TC)、低密度脂蛋白(low-density lipoprotein,LDL)、高密度脂蛋白(highdensity lipoprotein,HDL)、三酰甘油(triglyceride,TG)含量,并用气相色谱法(gas chromatography,GC)检测肠道短链脂肪酸含量,用液相色谱串联质谱法(liquid chromatography coupled to tandem mass spectrometry,LC-MS)检测肠道胆汁酸含量。结果雄性小鼠黄连素组肠道异丁酸(isobutyric acid,IBA)、异戊酸(isovaleric acid,IVA)、胆酸(cholic acid,CA)、鹅去氧胆酸(chenodeoxycholic acid,CDCA)、牛磺胆酸(taurocholic acid,TCA)及去氧胆酸(deoxycholic acid,DCA)含量明显高于对照组且随黄连素剂量升高而升高(P<0.05),血清TG水平随黄连素剂量升高而降低(P<0.01)。雌性小鼠黄连素组肠道胆酸及石胆酸(lithocholic acid,LCA)含量明显高于对照组且随黄连素剂量升高而升高(P<0.05),血脂及肠道短链脂肪酸含量的差异无统计学意义。结论低剂量黄连素可以促进正常饮食小鼠肠道短链脂肪酸和胆汁酸产生,降低正常饮食小鼠血清TG水平。低剂量黄连素的降血脂效果在雄性小鼠中更明显。

Objective To investigate the effects of low-dose berberine(BBR)on short chain fatty acids(SCFAs),bile acids(BAs) and serum lipids in normal chow-diet mice,and to explore the possible mechanism of berberine’s lipid-lowering effect. Methods Forty C57 BL/6 mice were randomly divided into three exposed groups and one control group,and three were 5 male and 5 female mice in each group.Mice of the three exposed groups were respectively administrated with 10,20 and 40 mg·kg-1·d-1 of BBR added drinking water for four weeks.Fat content,lean content,serum total cholesterol(TC),high-density lipoprotein(HDL),low-density lipoprotein(LDL),triglyceride(TG)were evaluated. SCFAs and BAs were examined by gas chromatography(GC) and liquid chromatography coupled to tandem mass spectrometry(LC-MS). Results For male mice,isobutyric acid(IBA),isovaleric acid(IVA),cholic acid(CA),chenodeoxycholic acid(CDCA),taurocholic acid(TCA)and deoxycholic acid(DCA)level increased with BBR dose and were higher than those in the control group(P<0.05),while TG level decreased with oral BBR dose(P<0.01).For female mice,CA and lithocholic acid(LCA)level increased with BBR dose and were higher than control group(P<0.05). There weren’t any differences of serum lipids and SCFAs in female mice. Conclusions Oral low-dose BBR can lower serum TG level in mice through generating SCFAs and BAs.Its lipid-lowering effects were more obvious in male mice.