Objective This study aimed to explore the therapeutic effect and mechanism of Xinyang Tablet on uremic cardiomyopathy from the perspective of inflammation-immunity. Methods A mouse model of uremic cardiomyopathy was established by 5/6 nephrectomy,and randomly divided into the model group and Xinyang Tablet group,with 15 mice in each group;another 15 sham-operated mice were used as the sham group. The Xinyang Tablet group was given Xinyang tablet (0.34 g/kg) by gavage after surgery,while the sham group and the model group were given an equal amount of 0. 9％ sodium chloride solution by gavage,for 8 weeks. The cardiac inflammation-immunity status and the regulatory effect and mechanism of Xinyang Tablet on uremic cardiomyopathy mice were analyzed by combining cardiac transcriptome data with bioinformatics methods. The mRNA expression levels of inflammatory factors and inflammation-immune cell-related markers in the hearts of mice in each group were detected by Real-time Quantitative PCR ( qPCR ) . The infiltration of inflammatory immune cells in the hearts of mice in each group was observed by the immunofluorescence method. Results GO enrichment analysis of cardiac tran-scriptome showed that Xinyang Tablet might inhibit multiple inflammation-related biological processes in the hearts of uremic cardiomyopathy mice. Cardiac transcriptome analysis showed that Xinyang tablet inhibited the levels of cardiac inflammatory factors ( IL-1β、IL-6、IL-18、TNF) and inflammation-immune cell-related markers ( CD86,CD72,Ly6c1,Itgb2 ),and reduced the infiltration of inflammation-immune cells ( neutrophils,monocytes,CD86+macrophages,CD72 hi macrophages) . The results of qPCR showed that the mRNA levels of IL-1β,IL-6,IL-18 and TNF in the hearts of the Xinyang Tablet group were significantly down-regulated compared with those of model group (P﹤0.05). Immunofluorescence results showed that the infiltration of neutrophils,monocytes and CD72 hi macrophages in the hearts of the Xinyang Tablet group were significantly reduced compared with those of the model group. In addition,gene set enrichment analysis ( GSEA) results showed that NF-κB,JNK,ERK1/2 and p38 MAPK signaling pathways were sig-nificantly inhibited in the Xinyang Tablet group (ES=-0.55;ES=-0.54;ES=-0.43;ES=-0.50). Conclusion Xinyang Tablet might improve uremic cardiomyopathy by inhibiting cardiac inflammation-immunity response.
关键词
尿毒症心肌病/心阳片/炎症免疫反应/免疫细胞
Key words
uremic cardiomyopathy/Xinyang Tablet/inflammation and immunity/immune cells
维普
万方数据