关键词: 血栓；发酵乳杆菌；肠道菌群；氧化应激；炎症

Abstract: In this study, the effect of 10-day intragastric administration of different concentrations (1 × 108 and 1 × 109 CFU/mL) of Lactobacillus fermentum CQPC04 (LF-CQPC04) suspension at a dose of 0.2 mL/(g mb·d) on blood coagulation, oxidative stress levels, inflammation levels and intestinal microbial composition in a mouse model of thrombosis induced by injecting 0.01 mL/(g mb·d) of 0.2% carrageenan was analyzed. Biochemical kits, hematoxylin-eosin (H&E) staining, and quantitative polymerase chain reaction (qPCR) were used to detect related indicators in serum and tissues, and high-throughput sequencing was used to observe the composition of gut microbiota. The experimental results showed that LF-CQPC04 could shorten the length of black tail, prothrombin time and thrombin time in mice with thrombosis, reduce the blood fibrinogen (FIB) concentration, and increase the activated partial thromboplastin time (APTT). LF-CQPC04 could also reduce malondialdehyde (MDA), tumor necrosis factor (TNF)-α, interleukin (IL)-6, nuclear factor (NF)-κB and IL-1β levels in serum, and increase superoxide dismutase (SOD) and catalase (CAT) activities. H&E staining showed that LF-CQPC04 could reduce tissue damage caused by tail vein thrombosis. LF-CQPC04 down-regulated the mRNA expression of the NF-κB p65, IL-6, TNF-α and IFN-γ genes in colon tissue, and up-regulated the mRNA expression of the genes encoding copper-zinc superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (Mn-SOD) and CAT. LF-CQPC04 could also down-regulate the mRNA expression of the genes encoding NF-κB p65, intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in tail vein tissue. The gene sequencing results of gut microbiota showed that LF-CQPC04 could increase the relative abundance of beneficial bacteria such as norank_f_Muribaculaceae, Lactobacillus, Bacteroides, Lachnospiraceae NK4A136, unclassified_f__Lachnospiraceae. These results indicated that LF-CQPC04 could inhibit thrombosis in mice, reduce oxidative stress and intestinal inflammation in mice with thrombosis, and regulate the intestinal flora, and high concentrations of LF-CQPC04 showed more pronounced effects, close to those of the drug heparin.

Key words: thrombosis; Lactobacillus fermentum; gut flora; oxidative stress; inflammation