趋化因子受体CXCR7在博莱霉素诱导的大鼠肺纤维化中的作用  

Role of chemokine receptor CXCR7 in bleomycin-induced lung fibrosis of rat

作　　者：李利华[1] 卢滨[1] 吴红科[1] 张浩[1] 姚菲菲[1] 

机构地区：[1]郑州人民医院呼吸科,河南郑州450003

出　　处：《现代预防医学》2015年第23期4357-4361,共5页Modern Preventive Medicine

摘　　要：目的检测并研究人CXC趋化因子受体7(CXCR7)在博莱霉素诱导的大鼠肺纤维化中的表达及其作用。方法通过气管内滴注博莱霉素方法建立35只SD大鼠肺纤维化模型,利用q RT-PCR和免疫印迹的方法检测肺脏组织中CXCR7 m RNA和蛋白在处理0 d、5 d、10 d、15 d、20 d、25 d、30 d后的表达变化。将30只雄性SD大鼠随机分为对照组、模型组和抑制剂组,对照组气管滴注生理盐水,抑制剂组滴注博莱霉素后静脉注射CXCR7特异性抑制剂CCX771。利用迪夫快速染色计数支气管肺泡灌洗液(BALF)中巨噬细胞、淋巴细胞、中性粒细胞的数量,同时利用试剂盒检测肺脏羟脯氨酸(HYP)的含量以及免疫印迹法检测I型胶原蛋白的表达,并制作病理切片,HE染色观察大鼠肺纤维化。结果博莱霉素处理后,大鼠肺脏CXCR7 m RNA和蛋白表达水平显著增高,并于处理20 d后达最高值。与对照组相比,模型组和抑制剂组大鼠体重显著降低、BALF细胞总数增高、淋巴细胞比例增加、肺脏HYP含量和I型胶原蛋白水平升高、肺纤维化病变明显。与模型组相比,抑制剂组体重恢复明显、BALF细胞总数降低、淋巴细胞比例减少、肺脏HYP含量和I型胶原蛋白水平降低、肺纤维化程度减轻。结论博莱霉素能诱导大鼠肺脏CXCR7的表达,抑制CXCR7活性可延缓肺纤维化的发展。Objective To analyze the expression and investigate the role of chemokine CXC motif receptor 7 （CXCR7） in bleomycin-induced lung fibrosis of rat. Methods SD rat model （n=35） was established by intratracheal bleomycin administration. The expression of CXCR7 mRNA and protein in lung tissues was analyzed by qRT-PCR and immunoblot after the treatment at 0d, 5d, 10d, 15d, 20d, 25d and 30d. 30 of SD male rats were randomly allocated into control group, model group and inhibitor group, respectively. The rats in control group were intranasally administrated with saline, while the animals in inhibitor group were intratracheally administrated with bleomycin and then intravenously injected with CCX771. The numbers of macrophage, lymphocyte, neutrophil were counted by Diff-Quick staining. The content of hydroxyproline （HYP） was determined by kits and the expression of type I collagen were analyzed by immunoblot. The lung tissues were sectioned and stained with HE to observe the severity of fibrosis. Results The expression of CXCR7 mRNA was significantly enhanced by bleomycin administration, reaching the highest level at 20d after the treatment. Compared with the control group, the weight of rats in the model group and inhibitor group reduced significantly, the number of BALF cell enhanced, the lymphocyte ratio increased. Conclusion Bleomycin could trigger the expression of CXCR7, regression of which might contribute to the attenuation of lung fibrosis development.

关 键 词：趋化因子受体7 博莱霉素 肺纤维化 CCX771 羟脯氨酸 I型胶原蛋白 

分 类 号：R113[医药卫生—公共卫生与预防医学]