骨髓间充质干细胞输注频次对矽肺大鼠肺纤维化的影响  

Effect of the frequency of bone marrow mesenchymal stem cell infusion on pulmonary fibrosis in silicosis rats

作　　者：张莹[1] 黄明[1] 陆丰荣[1] 蔡婷峰[1] 李瑞文[1] Zhang Ying;Huang Ming;Lu Fengrong;Cai Tingfeng;Li Ruiwen(Guangdong Province Hospital for Occupational Disease Prevention and Treatment,Guangzhou 510300,Guangdong Province,China)

机构地区：[1]广东省职业病防治院,广东省广州市510300

出　　处：《中国组织工程研究》2023年第19期2980-2985,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(81302396),项目负责人:黄明;广东省科技计划项目(2017A020215159),项目负责人:黄明;广东省医学科研基金(B2019200),项目负责人:张莹;广东省职业病重点实验室(2017B030314152)。

摘　　要：背景:课题组的前期研究显示骨髓间充质干细胞能减轻矽尘所致大鼠肺部炎症及肺纤维化,且未发现明显排斥反应和毒副作用。但至今为止,骨髓间充质干细胞治疗矽肺动物的报道几乎均为单次输注,未见多次重复输注与单次输注效果比较的报道。目的:研究骨髓间充质干细胞输注频次对矽肺大鼠肺纤维化的影响。方法:将SD大鼠随机分为正常对照组、模型组、单次输注组和多次输注组,每组6只。后3组大鼠经气管注入30 mg/mL的二氧化硅悬液1 mL,正常对照组注入等量生理盐水。单次输注组在染尘第28天经尾静脉输注细胞浓度为5×10^(9) L^(-1)的骨髓间充质干细胞悬液0.5 mL,多次输注组于染尘后第28,35,42天输注相同量的骨髓间充质干细胞,模型组和正常对照组输注等体积生理盐水。在染尘后第84天对各组大鼠进行肺部CT扫描,称量体质量和肺湿质量计算肺系数,取肺组织进行苏木精-伊红染色、Masson染色病理学观察,然后检测肺组织羟脯氨酸水平及血清转化生长因子β1水平。结果与结论:①肺部CT扫描显示:正常对照组大鼠肺部未见异常;模型组大鼠两肺野可见弥漫性、颗粒状高密度小阴影,网状纤维影、条索状影;单次输注组、多次输注组大鼠肺野的弥漫细小颗粒状阴影分布密度、纤维影面积均递减。②苏木精-伊红染色示:模型组可见弥漫矽结节,大范围融合,较多淋巴细胞浸润;单次输注组可见较多矽结节,局部融合,肺泡间隔有纤维组织增生、淋巴细胞浸润;多次输注组可见少量矽结节,肺间质纤维组织、淋巴细胞浸润少。③Masson染色示:模型组可见大量胶原纤维增生;多次输注组大鼠在增宽的肺泡间隔及支气管、血管周边可见少量胶原纤维;单次输注组的胶原纤维介于模型组、多次输注组之间。④肺系数、肺胶原容积分数、肺组织羟脯氨酸水平及血清转化生长因子β1水�BACKGROUND:Preliminary studies of the research team have shown that bone marrow mesenchymal stem cells can reduce pulmonary inflammation and pulmonary fibrosis in rats caused by silica dust,and no obvious rejection or side effects were found.However so far,almost all reports on the treatment of silicosis animals with bone marrow mesenchymal stem cells are single infusion,and there is no report comparing the effect of multiple repeated infusions and single infusions.OBJECTIVE:To investigate the effect of frequency of bone marrow mesenchymal stem cell infusion on pulmonary fibrosis in rats exposed to silica dust.METHODS:SD rats were randomly divided into normal control group,model group,single infusion group,and multiple infusion group,with 6 rats in each group.Rats in the latter three groups were treated with 1 mL SiO_(2) suspension at a concentration of 30 mg/mL by tracheal injection,and rats in normal control group were treated with equal volume of normal saline.The single infusion group was injected with 5×10^(9) L^(-1) bone marrow mesenchymal stem cell suspension via caudal vein on day 28 after dust exposure;the multiple infusion group was injected with bone marrow mesenchymal stem cell suspension on day 28,35 and 42 after dust exposure;the model group and the normal control group were injected with equal volume of normal saline.After 84 days of experiment,lung CT scan was performed to weigh and calculate lung coefficient in each group.Hematoxylin-eosin staining and Masson staining were performed to detect the levels of hydroxyproline in lung tissue and transforming growth factorβ1 in serum.RESULTS AND CONCLUSION:(1)Lung CT images showed that no abnormality was detected in rat lungs of the normal control group.In model group,small granular high-density shadows with diffused distribution and different sizes were observed in both lungs,as well as reticular fiber shadow or cable shadow.The density of the granular shadow distribution and the fiberoptic area were all decreased in the rat lung field of the single-

关 键 词：间充质干细胞 矽肺 大鼠 肺纤维化 输注频次 细胞移植 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R135.2