Protective effects and mechanisms of omega‐3 polyunsaturated fatty acid on intestinal injury and macrophage polarization in peritoneal dialysis rats

Abstract

Aim This study was conducted to investigate the chronic injury of peritoneal glucose injection on the peritoneum and intestine and the protective effects of omega‐3 polyunsaturated fatty acid (ω‐3PUFA) during peritoneal dialysis (PD). Methods Peritoneal dialysis animal models were established by intraperitoneal injection of 4.25% glucose for 28 days. Protein expression in ileum and peritoneum was measured by immunofloresence and immunohistochemistry. Protein expression in macrophages was measured by Western blot. Fibrosis was analyzed by Masson staining. Results Peritoneal dialysis significantly increased the structural injury and decreased junction‐related protein ZO‐1 and occludin expression in ileum, the expression of proteins relating to the activation of M2 (Erg2, IRF4), but not M1 (CD38, IRF5) macrophages. PD significantly increased the expression of TGF‐β1, VEGF and ALK5 protein in peritoneal tissues. PD significantly increased fibrosis (Masson staining) and the expression of fibroblast marker α‐SMA in peritoneal tissues. Injection of macrophage clean reagent and ω‐3PUFA significantly inhibited M2 activation, and decreased Masson staining, α‐SMA, TGF‐β1, VEGF and ALK5 protein expression in peritoneal tissues in PD treated rats. ω‐3PUFA injection significantly decreased PD‐induced injury in ileum and normalized the expression of ZO‐1 and occludin in the ileum of PD rats. Conclusion Omega‐3 fatty acids can provide a protective role on PD‐induced peritoneal fibrosis and injury of the intestine.

Omega-3 Polyunsaturated Fatty Acids and the Intestinal Epithelium—A Review

“…Fish oil, containing both EPA and DHA, has also exhibited protective effects on gut histology in other models, including reducing mucosal damage and preventing tight junction protein redistribution in a rat haemorrhagic shock model [ 45 ], as well as increasing villous length and crypt depth/villous length ratio in a female Sprague–Dawley rat model of peritoneal dialysis [ 51 ]. Fish oil also significantly increased villous height and improved histological architecture scores in β-lactoglobulin-treated female BALB/c mice, as well as preventing changes to short current circuit and tissue conductance in jejunal tissue [ 50 ].…”

Gut Microbiota, Macrophages and Diet: An Intriguing New Triangle in Intestinal Fibrosis

“…It has been shown that anti-inflammatory proprieties of n-3 PUFAs are underpinned by the polarisation of macrophages towards an M2 phenotype, therefore regulating the onset of HFD-induced tissue inflammation and metabolic perturbations [ 77 ]. Interestingly, n-3 PUFA are shown to exhibit anti-fibrotic effects by inhibiting M2 macrophage activation and TGF-β1 signalling in peritoneal fibrosis in mice [ 78 ]. Once again, these studies exhibit the dual role of M2 macrophages during inflammation and fibrosis.…”

Vascular endothelial growth factor-mediated peritoneal neoangiogenesis in peritoneal dialysis

“…Furthermore, results from our unpublished data and other groups indicate that M2 macrophages are the main participating sub-type during peritoneal injury. 114 Thus, M2-polarized macrophages also contribute to peritoneal neoangiogenesis and fibrosis.…”