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植物乳杆菌KSFY04通过调节核因子κB信号通路干预小鼠血栓形成的效果

Lactobacillus plantarum KSFY04 Inhibits Thrombosis in Mice by Regulating the Nuclear Factor Kappa B(NF-κB) Signaling Pathway
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摘要 通过角叉菜胶建立小鼠血栓模型,观察植物乳杆菌KSFY04(Lactobacillus plantarumKSFY04,LP-KSFY04)通过调节核因子κB(nuclear factorκB,NF-κB)相关炎症通路抑制血栓形成的效果。采用生化试剂盒和定量聚合酶链式反应(quantitative polymerase chain reaction,qPCR)检测小鼠血清、组织相关指标,苏木精-伊红(hematoxylin-eosin,HE)切片观察组织病变,并观察肠道微生物组成。结果:LP-KSFY04能够有效减轻血栓小鼠黑尾程度,并延长血栓小鼠活化部分凝血活酶时间、缩短凝血酶原时间、凝血酶时间及降低纤维蛋白原水平。LP-KSFY04还能够降低血栓小鼠血清、肾脏和肝脏炎症细胞因子肿瘤坏死因子α(tumor necrosis factor α,TNF-α)、白细胞介素(interleukin,IL)6和IL-1β的水平。病理学观察发现LP-KSFY04能够减轻血栓造成的肝肾组织病变和尾静脉血栓积累。qPCR结果显示,LP-KSFY04下调血栓小鼠尾静脉血管组织NF-κB p65、IL-6、TNF-α、细胞间黏附分子1(intercellular cell adhesion molecule 1,ICAM-1)、血管细胞黏附分子1(vascular cell adhesion molecule 1,VCAM-1)和选择素E的mRNA表达水平。同时,LP-KSFY04能够增加拟杆菌门、乳酸杆菌属、双歧杆菌属的丰度并降低厚壁菌门丰度。结论:LP-KSFY04对血栓小鼠具有减轻炎症和抑制血栓形成的作用,且高剂量LP-KSFY04作用更好,效果接近药物双嘧达莫。 This study observed the effect of Lactobacillus plantarum KSFY04(LP-KSFY04) against carrageenan-induced thrombosis in mice by regulating the NF-κB signaling pathway. Commercial biochemical kits and quantitative polymerase chain reaction(qPCR) were used to detect related indexes in mouse serum and tissues, and hematoxylin-eosin(HE) staining was used for histopathological examination. The composition of intestinal microbiota was examined as well. The results showed that LP-KSFY04 could effectively reduce the degree of black tail in thrombotic mice, prolong the activated partial thromboplastin time(APTT), and reduce the prothrombin time(PT), thrombin time(TT) and fibrinogen(FIB) level.LP-KSFY04 could also reduce the levels of inflammatory cytokines including tumor necrosis factor alpha(TNF-α),interleukin-6(IL-6) and interleukin-1 beta(IL-1β) in the serum, kidney and liver of thrombotic mice. Pathological observation showed that LP-KSFY04 could reduce liver and kidney lesions caused by thrombosis and the accumulation of tail vein thrombosis. qPCR results showed that LP-KSFY04 could down-regulate the mRNA expression of nuclear factor kappa-B p65(NF-κB p65), IL-6, TNF-α, intercellular cell adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1) and E-selectin. Moreover, LP-KSFY04 increased the relative abundance of Bacteroidetes, Lactobacillus and Bifidobacterium and decreased the relative abundance of Firmicutes. These results showed that LP-KSFY04 can reduce inflammation and inhibit thrombosis in thrombotic mice, and the effects of high concentration of LP-KSFY04 were most pronounced, which were close to those of dipyridamole.
作者 赵欣 刘佳 易若琨 骞宇 杨贞耐 ZHAO Xin;LIU Jia;YI Ruokun;QIAN Yu;YANG Zhennai(Chongqing Collaborative Innovation Center for Functional Food,Chongqing University of Education,Chongqing 400067,China;Beijing Advanced Innovation Center for Food Nutrition and Human Health,Beijing Technology&Business University,Beijing 100048,China)
出处 《食品科学》 EI CAS CSCD 北大核心 2022年第23期158-167,共10页 Food Science
基金 重庆市高校创新研究群体项目(CXQTP20033) 重庆市教育委员会科学技术研究项目重大项目(KJZD-M202201601) 重庆市自然科学基金面上项目(CSTB2022NSCQ-MSX0848) 重庆市留学人员回国创业创新支持计划项目(2205012980094776)。
关键词 血栓 植物乳杆菌 核因子ΚB信号通路 凝血 免疫 thrombus Lactobacillus plantarum nuclear factorκB signaling pathway coagulation immune
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