摘要
目的:探讨肠道菌群通过调节性T细胞(Treg)/吲哚胺2,3-双加氧酶-1(IDO1)轴信号通路参与动脉粥样硬化的进展。方法:将C57BL无特定病原体(SPF)级的5周雌性载脂蛋白E基因敲除(ApoE^(-/-))小鼠随机分为普通饲料处理组(NC组)和高脂饮食(含0.2%胆固醇,42%脂肪)处理组(HF组),每组10只。通过主动脉表面油红O染色和苏木精-伊红染色分析主动脉斑块和硬化损伤面积。采用流式细胞术分析脾细胞中CD_(4)^(+)CD_(25)^(+)叉头框蛋白p3(Foxp3)+Treg在CD_(4)^(+)T细胞中的百分比;蛋白免疫印迹法定量动脉吲哚胺2,3-双加氧酶(IDO),聚合酶链式反应(PCR)进行粪便微生物群分析。结果:与NC组比较,HF组小鼠主动脉斑块和硬化损伤面积增加(P<0.001),CD_(4)^(+)CD_(25)^(+)Foxp^(3+)/CD_(4)^(+)T比例和Foxp3 mRNA水平均降低(P<0.001)。与NC组比较,HF组小鼠IDO1含量降低(P<0.001)。小鼠斑块与Treg、IDO1呈负相关(r值分别为-0.87,-0.66,P<0.01)。厚壁菌门与动脉粥样硬化斑块呈正相关(r=0.64,P<0.01);放线菌与动脉粥样硬化斑块呈负相关(r=-0.74,P<0.01)。厚壁菌门与IDO1呈负相关(r=-0.59,P<0.05);拟杆菌门与IDO1呈正相关(r=0.67,P<0.01)。厚壁菌门与Treg呈负相关(r=-0.63,P<0.01);变形菌门与Treg呈正相关(r=0.61,P<0.01)。结论:肠道菌群改变可能通过Treg/IDO1信号通路,参与高脂饮食诱导的动脉粥样硬化进展。
Objective:To investigate gut microbiota participating in the progression of atherosclerosis through regulatory T cell(Treg)/indoleamine 2,3-dioxygenase-1(IDO1)axis signaling pathway.Methods:Five-week female apolipoprotein E gene knockout(ApoE^(-/-))mice of C57BL specific pathogen free(SPF)were randomly divided into ordinary feed treatment group(NC group)and high-fat diet(0.2%cholesterol,42%fat)treatment group(HF group),with 10 mice in each group.Aortic plaques and lesions were detected by oil red O staining and hematoxylin-eosin staining.The percentage of CD_(4)^(+)CD_(25)^(+)Foxp^(3+)Treg in spleen cells was detected by flow cytometry.Indoleamine 2,3-dioxygenase(IDO)was quantified by protein immunoblotting,and fecal microbiota was detected by polymerase chain reaction(PCR).Results:Compared with the NC group,the aortic plaque and hardened lesion area in the HF group increased(P<0.001),and the CD_(4)^(+)CD_(25)^(+)Foxp^(3+)/CD_(4)^(+)T ratio and Foxp3 mRNA level decreased(P<0.001).Compared with the NC group,the content of IDO1 in the HF group decreased(t=4.98,P<0.001).The plaques in mice were negatively correlated with Treg and IDO1(r values were-0.87 and-0.66,respectively,P<0.01).Firmicutes were positively correlated with atherosclerotic plaque(r=0.64,P<0.01).Actinomycetes were negatively correlated with atherosclerotic plaque(r=-0.74,P<0.01).Firmicutes were negatively correlated with IDO1(r=-0.59,P<0.05).Bacteroidetes were positively correlated with IDO1(r=0.67,P<0.01).Firmicutes were negatively correlated with Treg(r=-0.63,P<0.01).Proteobacteria were positively correlated with Treg(r=0.61,P<0.01).Conclusion:The changes of gut microbiota might participate in the progression of high-fat diet atherosclerosis via Treg/IDO1 signaling pathway.
作者
张裕祥
玛依拉·艾尼瓦尔
玛依拉·阿不都克力木
ZHANG Yuxiang;Maila·Enivar;Maila·Abudoukelimu(The Sixth Affiliated Hospital of Xinjiang Medical University,Urumqi 830002,Xinjiang,China)
出处
《中西医结合心脑血管病杂志》
2024年第18期3316-3320,共5页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
新疆维吾尔自治区卫生健康委员会自治区“青年科技人才-乡村振兴”项目(No.WJWY-XCZX202217)。
