摘要
目的 探讨骨髓来源间充质干细胞（MSCs）移植对大鼠肺气肿的疗效及其可能机制.方法 24只雌性SD大鼠按随机数字表法随机分为对照组、肺气肿组、MSCs移植组各8只,将肺气肿组与MSCs移植组大鼠烟雾暴露14周,制作肺气肿大鼠模型,予MSCs移植组大鼠通过尾静脉输注6-二乙酰基-2-苯基吲哚（DAPI）标记的骨髓来源MSCs.MSCs移植后第14、28天检测MSCs植入及转分化情况.MSCs移植8周,观察大鼠肺组织病理形态,并进行定量分析;检测凋亡细胞;测定血清和肺组织匀浆中氧化应激水平.结果 MSCs移植后第14、28天,受体肺组织内可见到DAPI标记的MSCs,其中一部分外源性MSCs表达表面活性蛋白C,即一部分植入肺部的MSCs分化成肺泡Ⅱ型上皮细胞.肺气肿组、MSCs移植组肺组织平均内衬间隔均显著高于对照组[（111 ±23）、（90±15）比（74±10）μm,平均肺泡数均显著低于对照组[（94±22）、（125±15）比（159±22）个/mm2]（均P＜0.05）;肺气肿组肺组织平均内衬间隔显著高于MSCs移植组,而平均肺泡数显著低于MSCs移植组（均P ＜0.05）.肺气肿组肺泡壁细胞凋亡指数显著高于MSCs移植组[（13.5±2.5）％比（4.8±0.7）％,P＜0.05].肺气肿组、MSCs移植组血清和肺组织中丙二醇均显著高于对照组[（4.3±0.8）、（3.7±0.4）比（3.0 ±0.4） nmol/ml和（5.4±0.5）、（4.8±0.4）比（4.2±0.6）nmol/mg,均P＜0.05];肺气肿组血清和肺组织中丙二醇均显著高于MSCs移植组（均P＜0.05）.肺气肿组、MSCs移植组血清和肺组织中超氧化物歧化酶均显著低于对照组[（8.7±0.8）、（9.6±0.7）比（10.5±0.9） U/ml和（56.3±13.4）、（70.2±11.0）比（84.9±13.0）U/mg,均P＜0.05];肺气肿组血清和肺组织中超氧化物歧化酶均显著低于MSCs移植组（均P＜0.05）.结论 骨髓来源MSCs移植可减轻吸烟所致的大鼠肺气肿,其可能机制是MSCs归巢、植入至受损伤的肺组织并分化为肺泡Ⅱ型上皮细胞,MSCs还可能通过抑制细胞凋亡、抑制氧化应激对肺气肿发挥治疗作用.
Objective To explore the effects of transplanting bone marrow mesenehymal stem cells （MSCs） on emphysema in rats and elucidate the possible mechanisms.Methods A total of 24 female Sprague-Dawley rats were randomly divided randomly into 3 groups of control,emphysema and MSCs transplantation （n =8 each）.The rat model of emphysema was established by 14-week exposure to cigarette smoking and then MSCs labeled with 4,6-diamidino-2-phenylindole （DAPI） were injected into recipient rats of MSCs transplantation group via tail veins.At 2 and 4 weeks post-transplantation,engraftment and differentiation of MSCs was determined.At 8 weeks post-transplantation,lung fissure sections were prepared for examining the morphological alterations.The apoptosis of alveolar septal cells was assessed.And the levels of oxidative stress in sera and lung were detected.Results At 2 and 4 weeks post-transplantation,MSCs labeled with DAPI could be found in recipient lungs,some of which differentiated into type Ⅱ alveolar epithelial cells.Mean linear intercept was higher in emphysema and MSCs transplantation groups than control group [（111 ±23） and （90 ± 15） vs （74 ± 10） μm],mean alveolar numbers were lower than control group [（94 ± 22） and （125 ± 15） vs （159 ± 22）/mm2] （all P 〈 0.05）;mean linear intercept was higher and mean alveolar numbers were lower in emphysema group than MSCs transplantation group （both P 〈 0.05）.The apoptotic index of alveolar wall cells in emphysema group was higher than MSCs transplantation group [（13.5 ± 2.5） % vs （4.8 ± 0.7） %,P 〈 0.05].Malondialdehyde of sera and lung in emphysema and MSCs transplantation groups was higher than control group [（4.3 ±0.8）,（3.7 ±0.4） vs （3.0 ±0.4） nmol/ml,（5.4 ± 0.5）,（4.8 ± 0.4） vs （4.2 ± 0.6） nmol/mg,all P 〈 0.05];malondialdehyde of sera and lung in emphysema group was higher than MSCs transplantation group （both P 〈 0.05）.Superoxide dismutase （SOD） of sera and lung in emphysema and MSCs transplantation groups was lower than control group [（8.7±0.8）,（9.6±0.7） vs （10.5 ±0.9） U/ml and （56.3 ±13.4）,（70.2±11.0） vs （84.9± 13.0） U/mg,all P 〈 0.05];SOD of sera and lung in emphysema group was lower than MSCs transplantation group （both P 〈 0.05）.Conclusion MSCs transplantation via tail vein may arrest the progression of emphysema in a cigarette-smoke-induced rat model of emphysema through a differentiation of injected MSCs into type Ⅱ alveolar epithelial cells and down-regulations of apoptosis and oxidative stress.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2015年第22期1731-1735,共5页
National Medical Journal of China
基金
云南省应用基础研究基金（2012FB106）
关键词
肺气肿
间质干细胞移植
治疗效果
大鼠
Pulmonary emphysema
Mesenchymal stem cell transplantation
Treatment outcome
Rats
