瓜蒌薤白白酒汤通过调节肠道菌群增加NR活性改善小鼠动脉粥样硬化的实验研究OA

Objective To investigate the mechanism by which Gualou Xiebai Baijiu Decoction(GXB)improves atherosclerosis(AS)by modulating gut microbiota(GM),promoting nitrate reductase(NR)activity.Methods Thirty-six male SPF ApoE-/-mice,aged 8 weeks,were divided randomly into Control,Model,Atorvastatin(Ato),and Gualou Xiebai Baijiu Decoction(GXB)groups(n=9 mice per group).Except for the Control group,the remaining mice were fed a high-fat,high-cholesterol diet for 16 weeks to establish the model,followed by 4 weeks of gavage intervention according to their respective group.Plaque and vascular morphology were observed by Oil red O and hematoxylin-eosin(HE)staining.Serum triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and serum/intestinal fluid nitrate(NO3-),nitrite(NO2-),and nitric oxide(NO)levels were measured.Macro-transcriptomic sequencing was applied to analyze GM structure and function.NR and nitrite reductase(NiR)activities in serum and intestinal fluid were assessed to validate the result of the macro-transcriptomic functional analysis.Results The pathological progression of AS was significantly improved in the GXB group compared with the Model group,while TG,TC,and LDL-C levels exhibited downward trends and HDL-C showed an opposite upward tendency.NO3-,NO2-,and NO levels in serum and intestinal fluids were significantly elevated.GXB reduced the richness of the GM in AS mice and improved its evenness.It also significantly decreased the abundance of Firmicutes and increased the abundance of anaerobic bacteria including Bacteroidetes and Verrucomicrobia.Functional analysis revealed that GXB promoted the activity of NR,activating the NO3--NO2--NO pathway,which increased endogenous NO levels.The GXB group also showed higher levels of serum/intestinal fluid NR and NiR compared with the Model group,consistent with the functional analysis.Conclusions GXB may improve the structure and function of the GM,increase the abundance of anaerobic gut bacteria,promote NR activity,activate the NO3--NO2--NO pathway,and elevate endogenous NO levels,thereby improving dyslipidemia and alleviating pathological AS damage.