Figure 2 Icariin alleviated inflammatory responses and oxidative stress in UUO mice. (A) Gene Ontology (GO) enrichment analysis of differentially expressed genes between the sham and UUO mice. (B) Heatmap of inflammatory response-related genes expression profiles of different groups based on the RNA-seq data set. The quantitative value=log10 FPKM. (C) Heatmap of key oxidoreductase-related gene expression of different groups based on the RNA-seq data set. The quantitative value=log10 FPKM. (D) Quantitative real-time PCR analysis of TNF-α, IL-1β and IL-6 mRNA levels. (E) MDA levels in the kidney. (F) SOD activity in the kidney. (G) Representative IHC images and quantification of F4/80 expression in the kidney from different groups. * p < 0.05, ** p < 0.01.
Icariin restored mitochondrial homeostasis in UUO mice.
Emerging discoveries demonstrate that mitochondrial damage is a critical step to trigger inflammation and oxidative stress in fibrotic diseases19,20. Our RNA-seq data also indicated that mitochondrion-related genes were significantly differentially expressed between the sham and UUO mice (Figure 2A). To further investigate whether icariin attenuated UUO-induced oxidative stress and inflammation by maintaining mitochondrial homeostasis, we then detected mitochondrial changes. The immunofluorescence staining of TOMM20, an outer mitochondrial membrane marker, revealed a significant reduction of mitochondria in kidneys from UUO mice (Figure 3A). Additionally, TEM observed evident mitochondrial damages, characterized by pronounced swelling, cristae loss, and mitochondrial membrane rupture in UUO mice (Figure 3B). However, treatment with icariin effectively alleviated these changes, indicating that icariin can improve UUO-induced mitochondrial abnormalities.