399 Down-Regulation of Peripheral Myelin Protein 22 (PMP22) Contributes to Impairment of Intestinal Barrier Integrity in Sepsis: Role of TNF-α and IFN-γ

Abstract

before IND. Subgroups of rats treated with IND or REIR+IND also received omeprazole (OME, 0.7 mg/kg OD, i.g.), as inhibitor of gastric acid secretion. At the end of treatments, blood samples were collected to evaluate hemoglobin (Hb) concentration (as an index of digestive bleeding). Small intestine was excised and processed for: 1) histological assessment of intestinal damage (percentage length of lesions over the total length examined); 2) assay of tissue myeloperoxidase (MPO) levels, as an index of neutrophil infiltration; 3) assay of tissue malondialdehyde (MDA) concentration, as an index of lipid peroxidation. Results. Rats treated with IND displayed a 13.3% mortality rate, while in groups treated with REIR+IND or OME+IND the mortality rate was lower (8.3% and 6.7%, respectively). No deaths were observed in controls or animals treated with OME+REIR+IND. IND treatment significantly decreased Hb levels (by 28%). While OME did not affect the Hb decrease, it was significantly lessened in rats treated with REIR+IND or OME+REIR+IND. IND treatment was associated with the occurrence of lesions in the jejunum and ileum. In both intestinal regions of rats treated with REIR+IND or OME+REIR+IND the percentage of lesions was significantly lower, as compared with rats receiving IND alone. The severity of lesions elicited by IND was reduced by co-treatment with OME in the jejunum, but not in the ileum. MPO and MDA levels in jejunum and ileum from IND-treated rats were significantly increased, as compared with controls. While OME was unable to affect these parameters, in rats treated with REIR+IND or OME+REIR+IND, MPO and MDA levels were not significantly different from those observed in controls. Results obtained are summarized in the enclosed Table. Conclusion. REIR treatment significantly prevents IND-induced intestinal damage, this entero-protective effect being associated with a decrease in tissue inflammation, oxidative stress and digestive bleeding. Administration of OME does not appear to affect the parameters related to intestinal damage, with few minor exceptions. Summary of the results obtained in the study