CCR5第一和第二胞外环特异性结合短肽对大鼠结肠炎的炎症细胞浸润及NF-κB/TNF-α信号通路的影响

摘要

目的 研究CC趋化因子受体5(CCR5)第一和第二胞外环特异性结合短肽对三硝基苯磺酸(TNBS)诱导的SD大鼠结肠炎的炎症细胞浸润及NF-κB/TNF-α信号通路的影响.方法 采用5%TNBS构建大鼠结肠炎模型,分别给予2种CCR5短肽干预,通过病理细胞学分析、蛋白免疫印迹法、PCR等方法分别评估其组织学、基因及蛋白质水平的变化.结果 与模型组相比,2组给予CCR5拮抗短肽的大鼠均表现为结肠炎组织学损伤减轻(P均<0.05),镜下可见中性粒细胞、淋巴细胞及巨噬细胞浸润减少(P均<0.05).同时,NF-κB/TNF-α信号通路相关的蛋白及mRNA表达水平也较之模型组明显下降(P均<0.05).结论 特异性结合CCR5第一和第二胞外环的短肽可明显抑制TNBS诱导的SD大鼠结肠炎症,其机制可能是通过抑制NF-κB/TNF-α信号通路的激活.%Objective To investigate the effect of the specific binding of antagonistic peptides to the first and second extracellular loops of CC chemokine receptor 5(CCR5)upon the inflammatory cell infiltration and NF-κB/TNF-αsignaling pathway in SD rats with colitis induced by trinitrobenzene sulfonic acid(TNBS). Methods The experimental SD rat models with colitis were induced by 5%TNBS,and intervened by two an-tagonistic peptides of CCR5. Pathological cytological analysis,western blot and PCR were performed to examine the histological changes of colon,proteins and mRNA levels of the NF-κB/TNF-αsignaling pathway. Results Compared with model group,the histological injuries of colitis were alleviated after administration of two antago-nistic peptides of CCR5(both P<0.05). The infiltration of neutrophils,lymphocytes and macrophages in rats treated with GH and HY peptides was significantly reduced(all P<0.05). Besides,the expression levels of the proteins and mRNAs related to the NF-κB/TNF-αsignaling pathway were also significantly down-regulated (all P<0.05). Conclusions Antagonistic peptides specifically binding to the ECL1 and ECL2 of CCR5 can evidently inhibit the inflammation in SD rats with TNBS-induced colitis,probably by suppressing the activation of the NF-κB/TNF-αsignaling pathway.