Effects of antagonistic peptides binding specifically with first and second extracellular loops of CCR5 on colitis rats induced by TNBS
10.3969/j.issn.1000-4718.2017.05.022
- VernacularTitle:CCR5第一、二胞外环特异性结合的拮抗短肽对TNBS诱导SD大鼠结肠炎的治疗作用
- Author:
Mei HU
;
Yangda SONG
;
Sixue LIU
;
Yihang SONG
;
Ximing SHEN
;
Huarong HUANG
;
Yingqiang ZHONG
- Keywords:
C-C chemokine receptor 5;
Antagonistic peptide;
Inflammatory bowel disease
- From:
Chinese Journal of Pathophysiology
2017;33(5):902-907
- CountryChina
- Language:Chinese
-
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 (ECL1:25, 35 and 45 mg/kg;ECL2:15, 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.