Effects of antagonistic peptides binding specifically with first and second extracellular loops of CCR5 on colitis rats induced by TNBS / 中国病理生理杂志

ABSTRACT

AIM:To study the effects of antagonistic peptides binding specifically with the first and second extracellular loops (ECL1 and ECL2) of C-C chemokine receptor 5 (CCR5) on the colitis rats induced by trinitrobenzenesulfonic acid (TNBS) and the mechanisms.METHODS:The colitis model of SD rats was induced by TNBS (100 mg/kg).The effects of 2 antagonistic peptides at different doses (ECL125, 35 and 45 mg/kg;ECL215, 25 and 35 mg/kg) on the model rats including the changes of disease activity index (DAI), colon macroscopic damage index (CMDI) and histological grading were observed.The mRNA and protein expression levels of TNF-α and COX-2 in the colonic mucosa were detected by real-time PCR and Western blot, respectively.RESULTS:Compared with model group, the changes of DAI, CMDI and histopathological injury of the rats treated with ECL2 antagonistic peptide HY at an appropriate dose were significantly reduced (P<0.05), and the protein and mRNA expression levels of TNF-α and COX-2 were significantly decreased (P<0.05).However, the effects of ECL1 antagonistic peptide GH on all scores and the expression levels of TNF-α and COX-2 were not obvious.CONCLUSION:ECL2 antagonistic peptide HY relieves TNBS-induced colitis in SD rats via down-regulating the expressions of TNF-α and COX-2 in the colonic mucosa, while the effect of ECL1 antagonist peptide GH was not obvious.