目的研究原花青素(Proanthocyanidin,PC)经肠道微生态途径调节脂质代谢。方法取成年雄性SD大鼠和长爪沙鼠,经基础饲料适应性喂养1周后,采集尾静脉血,收集血清,检测血清总胆固醇(Total cholesterol,TC)水平,并按TC及体重分为基础对照组、模型对照组、低剂量组(25 mg/kg PC)、中剂量组(100 mg/kg PC)、高剂量组(150 mg/kg PC)、阳性对照组(非诺倍特80 mg/kg),基础对照组饲以普通基础饲料,其余各组均饲以高脂饲料,每天灌胃1次,大鼠连续灌胃8周,沙鼠连续灌胃2周。大鼠8周末、沙鼠2周末,经股动脉采血,分离血清,处死前3 d收集72 h粪便。采用全自动生化仪检测TC、甘油三酯(Triglyceride,TG)、高密度脂蛋白胆固醇(High-density lipopro-tein cholesterol,HDL-C)、低密度脂蛋白胆固醇(Low-density lipoprotein cholesterol,LDL-C)、血总胆汁酸(Total bileacid,TBA)水平;循环酶法试剂盒测定粪TBA排出量水平;双抗体两步夹心ELISA法测定卵磷脂胆固醇酰基转移酶(Lecithin-cholesterol acyltransferase,LCAT)活性。解剖处死的大鼠和沙鼠,进行病理组织学分析。提取大鼠、沙鼠小肠、盲肠细菌基因组DNA,采用PCR-变性梯度凝胶电泳(Denatured gradient gel electrophoresis,DGGE)进行动物模型肠道微生态菌群多样性变化分析。结果模型对照组大鼠和沙鼠TC、TG水平明显高于基础对照组,差异有统计学意义(P<0.05),表明高脂模型建模成功。与模型对照组相比,各剂量组和阳性对照组大鼠、沙鼠TC、TG、LDL-C、血TBA水平均降低,LCAT活性、粪TBA排出量均明显升高,差异有统计学意义(P<0.05);各剂量组大鼠肝脏损伤、肝细胞肿胀、变性等病变程度明显减轻,肝组织病理变化明显改善。DGGE检测及图像分析显示,大鼠各剂量组肠道优势菌群多样性明显增加,随着PC干预剂量加大,中、高剂量组肠道菌群多样性明显减少;沙鼠低剂量组与模型对照组的肠道菌群结构基本相似,而中、高剂量组肠道菌群多样性明显减少,肠道优势菌群结构明显恢复。结论 100、150 mg/kg PC干预的实验动物模型中,肠道菌群结构多样性明显恢复,提示PC可通过肠道菌群这一靶标,进行脂质代谢的调节。 Objective To study the regulation of lipid metabolism by proanthocyanidin (PC) via intestinal microflora. Methods Adult male SD rats and Mongolian gerbils (Meriones unguiculatus) were fed with basal diet for 1 week. The tail vein blood was collected and the serum total cholesterol (TC) was measured. The levels of total cholesterol (TC) (25 mg / kg PC), medium dose (100 mg / kg PC), high dose (150 mg / kg PC), positive control group (fenofibrate 80 mg / kg). The basal control group was fed with normal basal diet. The other groups were fed with high-fat diet. The rats in each group were given gavage once daily for 8 weeks. The gerbils were given gavage for 2 weeks. At the end of 8 weeks, the gerbils were collected by the femoral artery 2 weeks after the sera were collected, and the sera were separated and collected for 72 hours before sacrificing. TC, triglyceride (TG), high-density lipopro-tein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL- C and total bile acid (TBA) were measured. The levels of TBA in feces were determined by the enzyme-linked immunosorbent assay (ELISA) and the activity of Lecithin-cholesterol acyltransferase (LCAT) . The sacrificed rats and gerbils were dissected for histopathological analysis. Genomic DNA was extracted from the small intestine and cecum of rats and gerbils. The changes of gut microbiota diversity in animal models were analyzed by PCR-denaturing gradient gel electrophoresis (DGGE). Results The levels of TC and TG in rats and gerbils in the model control group were significantly higher than those in the control group (P <0.05), indicating that the model of hyperlipidemia model was successfully established. Compared with the model control group, the TC, TG, LDL-C and blood TBA levels of gerbils were decreased, the activity of LCAT and the excretion of TBA of rats in each dose group and positive control group were significantly increased, the difference was statistically significant (P <0.05). The pathological changes of liver injury, hepatocyte swelling and degeneration of rats in each dose group were significantly alleviated, and the pathological changes of liver tissue were improved obviously. DGGE detection and image analysis showed that the diversity of dominant intestinal microflora in each dose group increased significantly. With the increase of PC intervention dose, the diversity of intestinal microflora in middle and high dose groups was significantly decreased. The model control group’s gut flora structure is basically similar, but medium and high dose group gut flora diversity was significantly reduced, gut dominant flora structure was significantly restored. Conclusion In the experimental animal model of 100 and 150 mg / kg PC intervention, the structural diversity of intestinal flora recovered obviously, suggesting that PC could regulate lipid metabolism through the target of intestinal flora.