肺内输入骨髓间充质干细胞对肺气肿大鼠慢性炎症的调控  

Intrapulmonary Delivery of Bone Marrow Mesenchymal Stem Cells Can Attenuate Chronic Inflammation of Emphysematous Rats

作　　者：管小俊[1] 宋琳[1] 郭雪君[1] 徐卫国[1] 

机构地区：[1]上海交通大学医学院附属新华医院呼吸科,上海200092

出　　处：《中国呼吸与危重监护杂志》2011年第6期520-526,共7页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：上海市基础研究重点项目(编号:09JC1410700);上海市卫生局科研青年项目(编号:2009Y024)

摘　　要：目的探讨移植骨髓间充质干细胞(MSC)对肺气肿大鼠慢性炎症的调控作用。方法烟熏法复制大鼠肺气肿模型。携带绿色荧光蛋白(GFP)的慢病毒转染MSC,烟熏大鼠肺内输入转染的MSC(n=4),小动物活体成像系统观察MSC的分布。36只SD大鼠随机分为对照组、肺气肿组及MSC干预组,评估支气管肺泡灌洗液(BALF)中细胞总数和分类计数,双抗体夹心酶联免疫吸附测定法(ELISA)检测BALF、血清中肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)水平,比色法检测肺组织丙二醛(MDA)含量,测量平均内衬间隔(MLI)评估肺气肿改变。结果肺内输入MSC 4周后,不同肺叶仍可见存活的MSC。与肺气肿组相比,MSC干预组BALF中细胞总数、血清和BALF中TNF-α及IL-1β水平、肺组织中MDA含量和MLI均明显减低,差异有统计学意义(P<0.01)。结论 MSC降低肺气肿大鼠气道及全身炎症介质TNF-α和IL-1β的表达,减轻气道炎症和氧化应激水平,对肺气肿有明显的治疗作用。Objective Bone marrow mesenchymal stem cells（MSCs） have been suggested to play an important role in the treatment of a variety of pulmonary diseases.The present study was aimed at evaluating the therapeutical effect of MSCs transplantation on emphysematous rats,and explore its influence in local and systemic inflammation.Methods Emphysema rat model was established by cigarette smoking.MSCs were transfected with lentivirus vector carrying green fluorecent protein（GFP） and the transfected MSCs in lung of smoking rats were detected by imaging system for small animals.Thirty-six SD rats were randomly divided into a control group,an emphysema group,and a MSCs transplantation group.The total and differential cell counts in bronchoalveolar lavage fluid（BALF） were measured.TNF-α and IL-1β levels in BALF and serum were measured by ELISA.Malonaldehyde （MDA） level in lung tissue was detected by chromatometry.Emphysema changes were evaluated by mean linear intercept（MLI） of lung under light microscope by HE staining.Results The transfected MSCs in different lung lobes were found to be alive at four weeks after intrapulmonary delivery.Compared with the emphysema group,the total cell count in BALF,TNF-α and IL-1β levels in BALF and serum,MDA level in lung tissue and MLI were significantly reduced in the MSCs transplantation group（P0.01）.Conclusions Transplantation of MSCs can mediate downregulation of TNF-α and IL-1β in BALF and serum,attenuate inflammation,oxidative stress and emphysema change of lung,suggesting that MSCs have significant therapeutic effects on emphysema.

关 键 词：慢性阻塞性肺疾病 慢性炎症 间充质干细胞 

分 类 号：R563.3[医药卫生—呼吸系统]