CCR5膜外一、二环模拟短肽对二甲苯致小鼠耳肿胀抑制作用的研究

Study on inhibition of mimic peptides binding specifically with the first and second extra-cellular domain of CC chemokine receptor 5 on mice ear engorgement induced by dimethyl benzene

目的研究与CC趋化因子受体5(CC chemokine receptor 5,CCR5)第一、二膜外襻特异结合的模拟肽,对二甲苯致小鼠耳肿胀抑制作用。方法用噬菌体随机7肽库筛选与CCR5特异结合的多肽序列,建立二甲苯致小鼠耳肿胀模型;合成4段氨基酸序列分别为STFTTTL(SL)、TPITQLL(TL)、SLPLPKP(SP)、QTSSAAL(QL)的CCR5模拟肽,将4段短肽分别腹腔内注射至耳肿胀模型小鼠,以阿司匹林为抗炎药效学实验的阳性对照药。分别通过称重小鼠左、右耳片和将小鼠耳片HE染色的方法,观察4段CCR5模拟肽对二甲苯致小鼠耳肿胀模型小鼠的抗炎活性。结果左、右耳片通过称重,HE染色后,发现4段CCR5模拟肽均能显著抑制二甲苯致小鼠耳肿胀模型小鼠耳朵水肿、充血和炎性细胞的浸润。抑制率分别为53.4%、47.3%、31.3%、25.2%,效果显著(P<0.05)。结论合成的4段CCR5模拟肽具有对二甲苯致耳肿胀模型小鼠明显的抑制作用,提示CCR5可能在二甲苯致耳肿胀模型小鼠的发病进程中发挥着重要的作用。

Objective To study the inhibition of mimic peptides binding specifically with the first and second extra-cellular domain of the CC chemokine receptor 5（CCR5） on mice ear engorgement induced by dimethyl benzene.Methods Phage display peptide library was used to screen peptide sequence bonding specifically with CCR5,then the model of mice ear engorgement was establish,and the four mimic peptides whose amino acid sequence are respectively STFTTTL（SL）、TPITQLL（TL）、SLPLPKP（SP）、QTSSAAL（QL） was synthesized,and the four peptides was injected into abdominal cavity of the ear engorgement model mice,take aspirin as the positive control of anti-inflammatory pharmacodynamics experiment.The left and the right mice ear tissue were obtained and weighted、HE stained,the four peptides was investigated the anti-inflammatory activity to mice ear engorgement induced by dimethyl benzene.Results After the left and the right mice ear tissue were weighted and HE stained,we find the four CCR5 mimic peptides had suppressed significantly mice ear engorgement induced by dimethyl benzene、hydrops and infiltrating of the inflammatory cells.The inhibition ratio is respectively 53.4%、47.3%、31.3%、25.2% that effect is significant（P0.05）.Conclusion All of the four short peptides respectively take the evident suppressing role on mice ear engorgement induced by dimethyl benzene.Thus this study indicated CCR5 may play a important role in the course of mice ear engorgement induced by dimethyl benzene.