黄芪-丹参对动脉粥样硬化大鼠肠道菌群的影响

Effect of Astragalus membranaceus-Salvia miltiorrhiza on Gut Microbiota in Rats with Atherosclerosis

目的研究黄芪-丹参对动脉粥样硬化(atherosclerosis,AS)大鼠肠道菌群的影响。方法将大鼠随机分为空白组、模型组、辛伐他汀组(1 mg/kg)、黄芪-丹参组(0.75 g/kg),采用高脂饲料喂养联合腹腔注射维生素D_(3)8周的方法复制AS模型,同时灌胃给药。采用自动生化分析仪检测大鼠血清总胆固醇(total cholesterol,TC)、三酰甘油(Triacylglycerol,TG)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)水平,采用酶联免疫吸附试验检测血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1β,IL-1β)水平,光学显微镜下观察胸主动脉病理变化,采用生物信息分析方法观察大鼠结肠内容物肠道菌群变化。结果与空白组比较,模型组大鼠血清TC、TG、LDL-C、TNF-α、IL-6、IL-1β水平明显升高(P<0.05),HDL-C水平明显降低(P<0.05),胸主动脉血管内皮损伤严重,可见明显蓝色钙状斑块,结肠内容物肠道菌群Berger-Parker、Simpson指数明显降低(P<0.05),放线菌门(Actinobacteria)、乳杆菌属(Lactobacillus)、双歧杆菌属(Bifidobacterium)和杜氏杆菌属(Dubosiella)群落丰度明显降低(P<0.05),变形菌门(Proteobacteria)、疣微菌门(Verrucomicrobia)以及布劳特氏菌属(Blautia)、unclassified_f_Ruminococcaceae和Lachnospiraceae_NK4A136_group群落丰度明显升高(P<0.05)。与模型组比较,黄芪-丹参组大鼠血清血脂和炎症因子水平明显改善(P<0.05),胸主动脉血管内皮无明显损伤及增厚,大致恢复正常,结肠内容物肠道菌群Berger-Parker、Simpson指数明显升高(P<0.05),放线菌门、乳杆菌属、双歧杆菌属和杜氏杆菌属群落丰度明显升高(P<0.05),变形菌门、疣微菌门以及布劳特氏菌属、unclassified_f_Ruminococcaceae和Lachnospiraceae_NK4A136_group群落丰度明显降低(P<0.05)。结论黄芪-丹参治疗AS的作用机制可能是通过调控肠道菌群改善血脂代谢和抑制炎症水平实现的。

Objective To investigate the effect of Astragalus membranaceus-Salvia miltiorrhiza on gut microbiota in rats with atherosclerosis(AS).Methods Rats were randomly divided into blank group,model group,simvastatin group(simvastatin 1 mg/kg),and Astragalus membranaceus-Salvia miltiorrhiza group(0.75 g/kg).A rat model of AS was established by high-fat diet combined with intraperitoneal injection of vitamin D_(3) for 8 weeks,and the drugs were given by gavage.An automatic biochemical analyzer was used to measure the serum levels of total cholesterol(TC),triacylglycerol(TG),and low-density lipoprotein cholesterol(LDL-C),and ELISA was used to measure the serum levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β);the bioinformatics method was used to observe the changes of gut microbiota in colon contents.Results Compared with the blank group,the model group had significant increases in the serum levels of TC,TG,LDL-C,TNF-α,IL-6,and IL-1β(P<0.05)and a significant reduction in high-density lipoprotein cholesterol(P<0.05),with severe vascular endothelial injury of the thoracic aorta and obvious blue calcium-like plaques;in terms of gut microbiota in colon contents,the model group had significant reductions in Berger-Parker and Simpson indices(P<0.05),as well as significant reductions in the abundance of Actinobacteria,Lactobacillus,Bifidobacterium,and Dubosiella(P<0.05)and significant increases in the abundance of Proteobacteria,Verrucomicrobia,Blautia,unclassified_f_Ruminococcaceae,and Lachnospiraceae_NK4 A136_group(P<0.05).Compared with the model group,the Astragalus membranaceus-Salvia miltiorrhiza group had significant improvements in the serum levels of blood lipids and inflammatory factors(P<0.05),with no obvious vascular endothelial injury or thickening of the thoracic aorta;in terms of gut microbiota in colon contents,the Astragalus membranaceus-Salvia miltiorrhiza group had significant increases in Berger-Parker and Simpson indices(P<0.05),as well as significant increases in the abundance of Actinobacteria,Lactobacillus,Bifidobacterium,and Dubosiella(P<0.05)and significant reductions in the abundance of Proteobacteria,Verrucomicrobia,Blautia,unclassified_f_Ruminococcaceae,and Lachnospiraceae_NK4 A136_group(P<0.05).Conclusion Astragalus membranaceus-Salvia miltiorrhiza exerts a therapeutic effect on AS rats by regulating gut microbiota to improve blood lipid metabolism and inhibit inflammation.