[1]杨 宇),袁晓梅),赵 欣),等.脐带间充质干细胞联合盐酸多西环素对肺纤维化小鼠的早期干预效果[J].郑州大学学报(医学版),2016,(04):489-494.
 YANG Yu),YUAN Xiaomei),ZHAO Xin),et al.Effect of umbilical cord-derived mesenchymal stem cell transplantation combined with doxycycline on mice with early stage pulmonary fibrosis[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2016,(04):489-494.
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脐带间充质干细胞联合盐酸多西环素对肺纤维化小鼠的早期干预效果()
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《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2016年04期
页码:
489-494
栏目:
论著
出版日期:
2016-07-20

文章信息/Info

Title:
Effect of umbilical cord-derived mesenchymal stem cell transplantation combined with doxycycline on mice with early stage pulmonary fibrosis
作者:
杨 宇1) 袁晓梅1) 赵 欣1)吴敏娜2)高新愿1)许芝山3) 钟根深3)# 郭悦鹏1)#
1)新乡医学院第一附属医院呼吸科 卫辉 453100;
2)新乡医学院基础医学院微生物教研室 新乡 453000;
3)河南省神经病学研究所生物治疗实验室 卫辉 453100
Author(s):
YANG Yu1)YUAN Xiaomei1)ZHAO Xin1)WU Minna2)GAO Xinyuan1) XU Zhishan3) ZHONG Genshen3) GUO Yuepeng1)
1)Department of Respiratory Medicine,the First Affiliated Hospital, Xinxiang Medical University, Weihui 453100;
2)Department of Microbiology,Basic Medical College, Xinxiang Medical University, Xinxiang 453000;
3)Laboratory of Biotherapy, Institute of Neurology in Henan Province, Weihui 453100
关键词:
脐带间充质干细胞 盐酸多西环素 肺纤维化 MMP-9 TIMP-1 小鼠
Keywords:
UC-MSC doxycycline hydrochloride pulmonary fibrosis MMP-9 TIMP-1 mouse
分类号:
R563
摘要:
目的:探讨脐带间充质干细胞(UC-MSCs)联合盐酸多西环素对肺纤维化小鼠的早期治疗效果及作用机制。方法:健康成年清洁级雌性C57BL/6小鼠40只,采用随机数字表法分为5组(n=8):对照组(气管内注入生理盐水,48 h后尾静脉注射生理盐水)、模型组(气管内注入博来霉素,48 h后尾静脉注射生理盐水)、盐酸多西环素组(气管内注入博来霉素,48 h后腹腔注射盐酸多西环素,隔日注射1次,连用4次)、干细胞组(气管内注入博来霉素,48 h后尾静脉注射UC-MSCs)、联合组(气管内注射博来霉素,48 h后尾静脉注射UC-MSCs联合腹腔注射盐酸多西环素,隔日注射1次,连用4次)。于造模第28天,取小鼠右肺组织行HE、Masson染色,进行肺泡炎评分及肺纤维化评分; 取左肺组织测定羟脯氨酸含量。采用免疫组化法检测MMP-9、TIMP-1蛋白的表达。结果:与模型组相比,干细胞组和盐酸多西环素组肺泡炎及肺纤维化程度减轻,羟脯氨酸含量降低,MMP-9蛋白的表达减弱,TIMP-1蛋白的表达升高,联合组以上指标改善最为显著(P<0.05)。结论:早期应用UC-MSCs联合盐酸多西环素能够显著减轻小鼠肺纤维化程度,其机制可能与提高TIMP-1表达、抑制MMP-9的表达有关。
Abstract:
Aim: To investigate the effect of umbilical cord-derived mesenchymal stem cells(UC-MSCs)transplantation and doxycycline in a mice model of pulmonary fibrosis and its mechanism.Methods: A total of 40 C57BL/6 female mice were randomly allocated into 5 groups.Mice in control group were intratracheally injected with NS under operating microscope. Mice in other groups were intratracheally injected with bleomycin. After 48 h, mice in the control and model group were injected with normal saline via the tail vein, mice in the doxycycline group were injected with doxycycline via abdomen, mice in the stem cell group were injected with UC-MSCs via the tail vein,and mice in the combination treatment group were given UC-MSCs plus doxycycline. On the 28th day, the lung tissue was collected. Histopathological scoring of alveolitis and pulmonary fibrosis was performed according to Szapiel's method. The contentof hydroxyproline was determined using alkaline hydrolysis method. The expressions of MMP-9 and TIMP-1 were determined using immunohistochemistry.Results: Compared with the model group, the alveolitis and pulmonary fibrosis in the stem cell group and doxycycline group alleviated, the content of hydroxyproline and the expression of MMP-9 decreased, while the expression of TIMP-1 increased, and the above parameters improved most significantly in the combination treatment group(P<0.05).Conclusion: UC-MSCs transplantation and doxycycline can relieve bleomycin-induced pulmonary fibrosis in mice. The mechanism might be related with inhibiting MMP-9 and inducing TIMP-1 expression.

参考文献/References:

[1] LEE AS,MIRA-AVENDANO I,RYU JH,et al.The burden of idiopathic pulmonary fibrosis: an unmet public health need[J].Respir Med,2014,108(7):955
[2] SHIMBORI C,GAULDIE J,KOLB M.Extracellular matrix microenvironment contributes actively to pulmonary fibrosis[J].Curr Opin Pulm Med,2013,19(5):446
[3] INAMDAR AC,INAMDAR AA.Mesenchymal stem cell therapy in lung disorders: pathogenesis of lung diseases and mechanism of action of mesenchymal stem cell[J].Exp Lung Res,2013,39(8):315
[4] 崔冰,胡卓伟.抗肺纤维化药物治疗研究进展[J].生理科学进展,2008,39(3):233
[5] SZAPIEL SV,ELSON NA,FULMER JD,et al.Bleomycin-induced interstitial pulmonary disease in the nude, athymic mouse[J].Am Rev Respir Dis,1979,120(4):893
[6] 李丽娜,王华,周蕾,等.博莱霉素诱导小鼠肺间质纤维化造模方式的选择[J].中国免疫学杂志,2010,26(3):254
[7] 魏燕华,刘桂桃.肺纤维化的治疗进展[J].临床肺科杂志,2014,19(2):336
[8] INOMATA M,KAMIO K,AZUMA A,et al.Pirfenidone inhibits fibrocyte accumulation in the lungs in bleomycin-induced murine pulmonary fibrosis[J].Respir Res,2014,15:16
[9] HASHIMOTO N,JIN H,LIU T,et al.Bone marrow-derived progenitor cells in pulmonary fibrosis[J].J Clin Invest,2004,113(2):243
[10]CHOI M,BAN T,RHIM T.Therapeutic use of stem cell transplantation for cell replacement or cytoprotective effect of microvesicle released from mesenchymal stem cell[J].Mol Cells,2014,37(2):133
[11]SUN Z,WANG C,SHI C,et al.Activated Wnt signaling induces myofibroblast differentiation of mesenchymal stem cells, contributing to pulmonary fibrosis[J].Int J Mol Med,2014,33(5):1097
[12]王红阳,刘晨,王雁,等.人脐带血干细胞抑制大鼠肺纤维化及肺巨噬细胞TGF-β1的表达[J].细胞与分子免疫学杂志,2013,29(1):31
[13]WANG BL,TU YY,FU JF,et al.Unbalanced MMP/TIMP-1 expression during the development of experimental pulmonary fibrosis with acute paraquat poisoning[J].Mol Med Rep,2011,4(2):243
[14]LU HT,SHEU MT,LIN YF,et al.Injectable hyaluronic-acid-doxycycline hydrogel therapy in experimental rabbit osteoarthritis[J].BMC Vet Res,2013,9:68
[15]FUJITA H,SAKAMOTO N,ISHIMATSU Y,et al.Effects of doxycycline on production of growth factors and matrix metalloproteinases in pulmonary fibrosis[J].Respiration,2011,81(5):420
[16]MOLYNEAUX PL,MAHER TM.The role of infection in the pathogenesis of idiopathic pulmonary fibrosis[J].Eur Respir Rev,2013,22(129):376

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备注/Memo

备注/Memo:
*国家自然科学基金资助项目 81201765; 新乡医学院研究生科研创新支持计划资助项目 YJSCX20406Z
#通信作者:郭悦鹏,男,1957年10月生,本科,主任医师,教授,研究方向:呼吸疾病的基础与临床,E-mail:guoyuepeng2517@163.com; 钟根深,男,1981年3月生,博士,副教授,研究方向:生物治疗的基础及临床研究,E-mail:zhonggs@xxmu.edu.cn
更新日期/Last Update: 2016-07-20