巨噬细胞叶酸受体β表达对博莱霉素诱导小鼠肺纤维化的影响  

Effect of macrophage FRβ expression on bleomycin induced pulmonary fibrosis in mice

作　　者：姚梓平[1] 秦慧娟[1] 何春辉[1] 

机构地区：[1]新疆医科大学第一附属医院中医内科,乌鲁木齐830054

出　　处：《重庆医学》2018年第7期887-891,895,共6页Chongqing medicine

基　　金：新疆维吾尔自治区自然科学基金资助项目(2016D01C175)

摘　　要：目的探讨巨噬细胞的叶酸受体β(FRβ)表达对博莱霉素诱导小鼠肺纤维化的影响。方法将小鼠分为正常组、对照组和实验组,每组各6只。对小鼠进行肺纤维化(PF)诱导,实验组给予免疫毒素,对照组给予对照蛋白,正常组不做任何处理。小鼠的左肺用于组织学分析,右肺用于羟脯氨酸分析,检测巨噬细胞的FRβ表达对博莱霉素诱导小鼠PF的影响,常规特发性肺纤维化(UIP)患者肺部巨噬细胞的FRβ表达情况。结果巨噬细胞FRβ表达主要存在于UIP患者和博来霉素诱导的PF小鼠的肺部纤维化区域;经鼻给予小鼠免疫毒素能够显著增加存活率(P=0.003),并降低博来霉素诱导的PF中总羟脯氨酸和纤维化水平(P=0.009、0.014);免疫组化结果显示免疫毒素能降低博莱霉素诱导的PF小鼠肺部肿瘤坏死因子(TNF)-α,趋化因子CCL2和CCL12细胞的数量(均P=0.000)。结论巨噬细胞的FRβ表达在特发性肺纤维化(IPF)中起着致病性作用,针对表达FRβ的巨噬细胞的靶向治疗也许是治疗IPF的有效方法。Objective To investigate the effect of macrophage FRβexpression on bleomycin induced pulmonary fibrosis（PF）in mice.Methods The rats were divided into the normal group,control group and experimental group,6 cases in each group.The mice were performed the PF induction.The experimental group was treated with immunotoxin,the control group was given the contrast protein and the normal group was not treated.The mouse left lung was used for histological analysis,and the right lung was used for hydroxyproline analysis.The effect of macrophage FRβexpression on bleomycin induced pulmonary fibrosis in mice and the pulmonary macrophage FRβexpression in the patients with idiopathic pulmonary fibrosis（UIP）were detected.Results The macrophage FRβexpression mainly existed in the patients with UIP and pulmonary fibrosis area of PF mice induced by bleomycin;the survival rate was significantly increased by giving the mice immunotoxin with nose（P=0.003）,and the level of total hydroxyproline and fibrosis of PF mice induced by bleomycin was decreased（P=0.009,0.014）;immunohistochemistry results showed that immunotoxin could reduce the cells number of lung tumor necrosis factor（TNF）-α,chemotactic CCL2 and CCL12 cells in PF mice induced by bleomycin（P=0.000）.Conclusion The FRβexpression of macrophages plays a pathogenic role in IPF,and the targeted therapy of FRβexpression in macrophages may be an effective method for the treatment of IPF.

关 键 词：巨噬细胞 博来霉素 免疫毒素类 肺纤维化 叶酸受体β 

分 类 号：R285.5[医药卫生—中药学]