2-Deoxy-D-glucose Alleviates Collagen-Induced Arthritis of Rats and Is Accompanied by Metabolic Regulation of the Spleen and Liver

Figures

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  Figure 1. The effect of 2-DG on CIA rats. (A) Photographs of paws from the CIA rats following PBS (n=6) or 2-DG (n=6) treatment. The healthy rats (NC) treated with PBS (n=6) or 2-DG (n=6) were used as controls. (B) Representative images of the histological examination of the rat joint synovial tissues (200 x magnification). (C) Clinical scores of the CIA rats treated with PBS or 2-DG. *p < 0.05.

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  Figure 2. The immune effect of 2-DG treatment on CIA rats. (A) B cell proportion in peripheral blood of the CIA rats treated with PBS (n=6) or 2-DG (n=6). The healthy rats (NC) treated with PBS (n=6) or 2-DG (n=6) were used as controls. (B) CD4+ T cell and CD8+ T cell proportions in peripheral blood of the rats. (C) Proinflammatory cytokine levels in peripheral blood of the rats. (D) Th1 (IFN-γ and IL-2) and Th2 (IL-4, IL-5 and IL-13)-related cytokine levels in the rats. *p < 0.05, **p < 0.01, and ***p < 0.001.

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  Figure 3. The effect of 2-DG treatment on lactate and pyruvate production in CIA rats. The concentrations of lactate (A) and pyruvate (B), as well as the lactate/pyruvate ratio (LPR) (C), were measured in the peripheral blood of the rats that were treated with PBS (n=6) or 2-DG (n=6). The healthy rats (NC) treated with PBS (n=6) or 2-DG (n=6) were used as controls. **p < 0.01, ***p < 0.001 and ns, not significant .

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  Figure 4. The effect of 2-DG treatment on the mRNA expression of glycolytic enzymes in PBMCs of CIA rats. The CIA rats were treated with PBS (n=6) or 2-DG (n=6). The healthy rats (NC) treated with PBS (n=6) or 2-DG (n=6) were used as controls. The mRNA levels were determined using quantitative real-time PCR. *p < 0.05, **p < 0.01, ***p < 0.001, ns, not significant.

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  Figure 5. Metabolomic analysis of the rat plasma. (A) Volcano plots were prepared by plotting the log (base 2) of the FC and p values of t-test results (base 10) for differentially expressed plasma metabolites in rats between pairs of the four groups including healthy control (P-H) (n=6), CIA rats (P-C) (n=6), CIA rats treated with 2-DG (P-T) (n=6), and healthy rats treated with 2-DG (P-K). (B) The pathway analysis was performed based on the KEGG pathway database. The bubble chart shows the pathways that were enriched with DEMs in the plasma between pairs of the four groups.

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  Figure 6. Metabolomic analysis of the rat livers. (A) Volcano plots were prepared by plotting the log (base 2) of the FC and p values of t-test results (base 10) for differentially expressed metabolites in rat livers between pairs of the four groups including the healthy control (L-H) (n=6), CIA rats (L-C) (n=6), CIA rats treated with 2-DG (L-T) (n=6), and healthy rats treated with 2-DG (L-K) (n=6). (B) The pathway analysis was performed based on the KEGG pathway database. The bubble chart shows the pathways that were enriched with DEMs in the liver between the four rat groups.

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  Figure 7. Metabolomic analysis of the rat spleens. (A) Volcano plots were prepared by plotting the log (base 2) of the FC and p values of t-test results (base 10) for rat spleen metabolites between pairs of the four groups, including the healthy controls (S-H) (n=6), CIA rats (S-C) (n=6), CIA rats treated with 2-DG (S-T) (n=6), and healthy rats treated with 2-DG (S-K) (n=6). (B) The pathway analysis was performed based on the KEGG pathway database. The bubble charts show pathways that were enriched with DEMs in the spleen between the four rat groups.

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  Figure 8. Transcriptomic analysis of the rat livers. (A) MA (M-versus-A) plots showing differential expressing genes in rat livers between the four rat groups including healthy control rats (L-H) (n=6), CIA rats (L-C) (n=6), CIA rats treated with 2-DG (L-T) (n=6), and healthy rats treated with 2-DG (L-K) (n=6). (B) Bubble charts showing the top 20 differentially enriched pathways in the rat liver among the four rat groups.

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  Figure 9. Transcriptomic analysis of the spleens of rats. (A) MA (M-versus-A) plots of differential expressing genes in spleens between the four rat groups including healthy controls (S-H) (n=6), CIA rats (S-C) (n=6), CIA rats treated with 2-DG (S-T) (n=6), and healthy rats treated with 2-DG (S-K) (n=6). (B) Bubble charts showing the top 20 differentially enriched pathways in the rat spleen among the four rat groups.