JIB-04 inhibits aortic dissection by regulating the polarization of M1 macrophages
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.Methods Bone marrow-derived macrophages were ex-tracted 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 reac-tion(PCR),and the protein expression level of M1-type macrophage markers was detected by protein im-munoblotting assay.Differences between the two groups were compared using an independent samples t-test.Results Flow 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 re-sults 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 in-tervention group was 1.18±0.17.The protein expression of iNOS in the JIB-04 drug intervention group was decreased significantly as compared with that in the LPS-stimulated group(t=4.84,P＜0.05).Conclusion JIB-04 can regulate the occurrence of aortic dissection by inhibiting the polarization of macro-phage M1.
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