骨髓间充质干细胞对染矽尘大鼠肺损伤修复作用研究  

Effects of bone marrow mesenchymal stem cells on the repair of lung injury of rats caused by silica dust

作　　者：黄明[1] 周永梅[2] 宋向荣[1] 黄昆洁 葛怡琛[1] 赖关朝[1] 梁伟辉[1] 曾小菁[2] 曾子芳[1] 

机构地区：[1]广东省职业病防治院,广东省职业病防治重点实验室,广东广州510300 [2]贵阳医学院,贵州贵阳550004

出　　处：《中国职业医学》2014年第4期361-366,共6页China Occupational Medicine

基　　金：国家自然科学基金(81302396);国家临床重点专科建设项目(2011-09);广东省职业病防治重点实验室(2012A061400007);广东省医学科学研究基金资助项目(A2010016);广东省职业病防治院专项课题(Z200907)

摘　　要：目的观察骨髓间充质干细胞(MSC)对矽尘所致大鼠肺损伤的修复作用。方法取7只无特定病原体级健康雄性SD大鼠培养MSC,并取30只同类SD大鼠随机分为对照组、染矽尘组和MSC输注组。对照组大鼠气管内注射1.0 ml生理氯化钠溶液,染矽尘组和MSC输注组均气管内注射1.0 ml质量浓度为40 g/L的矽尘混悬液,其后,MSC输注组大鼠鼠尾静脉注射0.5 ml细胞密度为5×109/L的MSC,其余2组鼠尾静脉注射0.5 ml生理氯化钠溶液。第28天处死大鼠,观察肺组织病理学改变情况,并检测肺脏器系数、肺灌洗液(BALF)细胞计数和血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、肌酸激酶(CK)、乳酸脱氢酶(LDH)活力和尿素氮(BUN)、肌酐(Cr)水平。结果染矽尘组和MSC输注组大鼠的肺脏器系数均高于对照组[(0.528±0.044)%vs(0.435±0.027)%,(0.492±0.042)%vs(0.435±0.027)%,P<0.05],MSC输注组肺脏器系数低于染矽尘组[(0.492±0.042)%vs(0.528±0.044)%,P<0.05]。病理学检查显示:对照组无肺部炎症、矽结节和纤维化改变;染矽尘组大鼠肺部炎症最严重,并可见大量矽结节和胶原纤维沉积;与染矽尘组比较,MSC输注组肺部炎症减轻,矽结节数量减少,胶原纤维沉积面积较小。对照组大鼠BALF的总细胞数、巨噬细胞、中性粒细胞和淋巴细胞计数分别为(5.86±1.28)×106/L、(5.45±1.30)×106/L、(0.11±0.04)×106/L和(0.23±0.10)×106/L,染矽尘组的分别为(10.37±2.29)×106/L、(6.57±1.34)×106/L、(3.18±0.98)×106/L和(0.58±0.10)×106/L,MSC输注组的分别为(8.31±1.59)×106/L、(6.15±1.49)×106/L、(1.66±0.36)×106/L和(0.43±0.10)×106/L;染矽尘组和MSC输注组大鼠BALF的总细胞数、中性粒细胞和淋巴细胞计数均分别高于对照组(P<0.05),MSC输注组上述3个指标均低于染矽尘组(P<0.05)。3组血清ALT、AST、CK、LDH活力及BUN、Cr水平分别比较,差异均无统计学意义(P>0.05)。结论骨髓MSC对矽尘导致的肺部炎症及纤�Objective To observe the effects of bone marrow mesenchymal stem cells （MSC） on rats＇ repairing lung injury caused by silica dust. Methods Bone marrow MSC were isolated from 7 specific pathogen free healthy male SD rats, cultured and amplified in vitro, while other 30 rats were randomly divided into a control group, a silicotic group and a MSC infusion group. Each rat in silicotic group and MSC infusion group was injected intratracheally 1.0 ml silica （ mass concentration 40 g/L） while in the control group was given 1.0 ml normal saline. Then, MSC infusion group was injected 0. 5 ml MSC （cell density was 5 × 10^9/L） through the tail vein, while the other groups were given 0. 5 ml normal saline. Rats were executed at the twenty-eighth day. The pathomorphological changes in lung tissues were observed, while pulmonary index, cell counts of bronchoalveolar lavage fluid （BALF） , activities of serum alanine aminotransferase （ALT） , aspartate aminotransferase （AST） , creatine kinase （CK）, lactate dehydrogenase （LDH） and serum urea nitrogen （BUN）, creati-nine （Cr） levels were detected. Results The lung coefficients of silicotic group and MSC infusion group were higher than that of the control group respectively [ （ 0. 528 ± 0. 044 ） % vs （0. 435 ± 0. 027 ） %, （ 0. 492 ± 0. 042 ） % vs （ 0. 435 ±0. 027） %, P 〈 0. 05 ], while MSC infusion group was lower than that of the silicotic group [ （ 0. 492 ±0. 042 ） % vs （0. 528 ± 0. 044） % , P 〈 0. 051. Histopathology examination showed that ： there were no pulmonary inflammation, silicotic nodule and pulmonary fibrosis observed in the control group; pulmonary inflammation was the most serious in silicotic group, and there was a large number of silicotic nodules and collagen fiber deposition ; pulmonary inflammation of MSC infusion group was lighter than that of silicotic group while the number of silicotic nodule and the collagen fiber deposition area were lesser. The number of BALF total cells, macroph

关 键 词：骨髓间充质干细胞 二氧化硅 矽肺 肺损伤 矽结节 肺纤维化 肺部炎症 大鼠 

分 类 号：R135.12[医药卫生—劳动卫生]