JIB-04通过调节M1型巨噬细胞极化抑制主动脉夹层发生  

JIB-04 inhibits aortic dissection by regulating the polarization of M1 macrophages

作　　者：王星博 龚福汉 蒋丁胜 魏翔[1] Wang Xingbo;Gong Fuhan;Jiang Dingsheng;Wei Xiang(Department of Cardiothoracic and Vascular Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Department of Cardiology,Tongren People's Hospital,Tongren 554300,China)

机构地区：[1]华中科技大学同济医学院附属同济医院心脏大血管外科,武汉430030 [2]铜仁市人民医院心血管内科,铜仁554300

出　　处：《中华实验外科杂志》2024年第3期523-525,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金面上项目(82270511);贵州省卫生健康委科学技术基金项目(gzwkj2023-311)。

摘　　要：目的分析组蛋白去甲基酶抑制剂JIB-04对于小鼠骨髓来源巨噬细胞M1极化的影响,探究其与主动脉夹层发生之间的关系。方法提取小鼠骨髓来源巨噬细胞,诱导巨噬细胞M1分化,给予JIB-04药物干预,并通过流式细胞术检测M1型细胞极化率,实时荧光定量聚合酶链反应(PCR)实验检测炎性标志物的RNA表达水平,蛋白质免疫印迹实验检测M1型巨噬细胞标志物的蛋白表达水平,两组间差异比较采用独立样本t检验。结果流式细胞实验显示JIB-04干预组的M1巨噬细胞阳性群比例为(21.90±0.65)%,脂多糖(LPS)刺激组为(35.81±0.49)%,药物干预组相较于LPS刺激组的阳性群比例差异有统计学意义(t=29.36,P<0.01);PCR实验结果显示LPS刺激组的M1型巨噬细胞的炎性标志物一氧化氮合酶(iNOS)相对RNA表达水平为170.60±5.92,药物干预组为38.21±3.41,JIB-04药物干预组的M1型巨噬细胞的炎性标志物低于LPS刺激组,差异有统计学意义(t=38.54,P<0.01),且其余炎性标志物结果同iNOS一致;蛋白免疫印迹实验结果显示LPS刺激组的iNOS的蛋白表达含量为3.51±0.94,药物干预组的iNOS表达含量为1.18±0.17,JIB-04药物干预组的iNOS蛋白表达含量低于LPS刺激组且差异有统计学意义(t=4.84,P<0.05)。结论JIB-04可以通过抑制巨噬细胞M1极化进而调控主动脉夹层的发生。Objective To analyze the effect of Jumonji structural domain inhibitor JIB-04 on M1 polarization of mouse bone marrow-derived macrophages and to explore the relationship between JIB-04 and the occurrence of aortic coarctation development.MethodsBone marrow-derived macrophages were extracted from mouse and were induced to polarize toward macrophages of M1 phenotype.The polarization rate of M1-type cells was detected by flow cytometry under the intervention of JIB-04.The expression of bio-markers of M1 macrophage was detected by real-time fluorescence quantitative polymerase chain reaction(PCR),and the protein expression level of M1-type macrophage markers was detected by protein immunoblotting assay.Differences between the two groups were compared using an independent samples t-test.ResultsFlow cytometry experiments showed that the proportion of positive M1 macrophage clusters was(21.90±0.65)%in the JIB-04 intervention group and(35.81±0.49)%in the lipopolysaccharide(LPS)-stimulated group,and there was a statistically significant difference in the proportion of positive clusters between the drug-intervention group and the LPS-stimulated group(t=29.36,P<0.01).The results of real-time PCR showed that the relative RNA expression level of the inflammatory marker nitric oxide synthase(iNOS)in M1-type macrophages in the LPS-stimulated group was 170.60±5.92,while that in the drug-intervention group was 38.21±3.41,and that the inflammatory markers in M1-type macrophages in the JIB-04 drug-intervention group were significantly decreased in the JIB-04 drug-intervention group as compared with those in the LPS-stimulated group(t=38.54,P<0.01),and the results of the rest of the inflammatory markers were consistent with iNOS.The results of protein immunoblotting experiments showed that the protein expression of iNOS in the LPS-stimulated group was 3.51±0.94,and that in the drug intervention group was 1.18±0.17.The protein expression of iNOS in the JIB-04 drug intervention group was decreased significantly as compared with

关 键 词：主动脉夹层 JIB-04 巨噬细胞极化 

分 类 号：R543.1[医药卫生—心血管疾病]