间充质干细胞对呼吸机引起的肺损伤的保护作用及机制

The protective role of mesenchymal stem cells in ventilator-induced lung injury in rats

目的 探讨间充质干细胞（MSCs）对大鼠呼吸机所致肺损伤的保护作用及其机制.方法 SD大鼠30只,采用大潮气量机械通气法制备呼吸机所致肺损伤的大鼠模型,按照随机数字表法分为3组,假手术组、对照组和MSCs治疗组,每组各10只.机械通气后4h处死大鼠,分别进行大鼠肺组织病理及损伤评分、肺组织中性粒细胞浸润数量测定和肺泡灌洗液中炎性因子水平测定.结果 机械通气4h后,MSCs治疗组大鼠肺组织损伤评分为（4.23±1.64）分,显著低于对照组[（7.31 ±2.15）分,t=6.427,P＜0.01],和假手术组比较差异无统计学意义[（1.97±1.31）分,t=2.22,P＞0.05].假手术组、对照组和MSCs治疗组大鼠肺组织中性粒细胞浸润数量分别为（9.27±4.55）、（26.37 ±9.44）、（15.33 ±6.62）个.MSCs治疗组中性粒细胞浸润数量和与对照组比较差异有统计学意义（t=3.011,P＜0.05）,与假手术组比较差异无统计学意义（t=1.234,P＞0.05）.MSCs治疗组大鼠肺泡灌洗液中白细胞介素（IL）-1β、IL-6和肿瘤坏死因子-α（TNF-α）水平分别为（70.40 ±31.40）、（41.37±14.34）和（47.60±10.23） ng/L,显著低于对照组（170.20±58.90）、（99.30±31.97）和（114.30±24.60） ng/L,差异均有统计学意义（=5.04,P＜0.01;t=3.09,P＜0.05;t =6.33,P＜0.01）,和假手术组比较差异无统计学意义[（37.90±12.70） ng/L,t=1.27,P＞0.05;（29.20 ±9.11） ng/L,t=2.33,P＞0.05;（39.44±12.14） ng/L,t =0.91,P＞0.05].结论 MSCs可以减轻大潮气量机械通气所致的肺部组织损伤、肺部中性粒细胞浸润、降低局部炎性介质的释放,对呼吸机所致肺损伤具有保护作用.

Objective To investigate the protective role of mesenchymal stem cells （MSCs） in ventilator-induced lung injury （VILI） in rats and its mechanisms.Methods Rat VILI model was established by high tidal volume ventilation in SD rats and randomly divided into 3 groups：sham operated group,control group and MSCs treatment group （n =10 per groups）.The lung tissue injury,lung polymorphonuclear （PMN） cells counts and pro-inflammatory cytokines [interleukin （IL）-1β,IL-6 and tumor necrosis factor-α （TNF-α）] levels in bronchoalveolar lavage fluid （BALF） were measured 4 h after mechanical ventilation.Results 4 h after mechanical ventilation,the lung tissue injury score of MSCs group was 4.23 ± 1.64,significantly lower than that of control group （7.31 ± 2.15,t =6.427,P 〈 0.01）,and similar to the sham group （1.97 ± 1.31,t =2.22,P 〉 0.05）.The lung PMN counts of three groups were 9.27 ±4.55,26.37 ±9.44 and 15.33 ±6.62,respectively.The PMN counts of MSCs group was significantly lower than that of saline group （t =3.011,P 〈 0.05） and similar to the sham group （t =1.234,P 〉0.05）.The IL-1β,IL-6 and TNF-α levels in BALF of MSCs group was （70.40 ± 31.40）,（41.37 ±14.34） and （47.60 ± 10.23） ng/L,respectively,significantly lower than that of control group [（170.20 ±58.90） ng/L,t=5.04,P〈0.01;（99.30 ±31.97） ng/L,t=3.09,P〈0.05;（114.30 ±24.60） ng/L,t =6.33,P 〈 0.01] and similar to the sham group [（37.90 ± 12.70） ng/L,t =1.27,P〉0.05;（29.20±9.11） ng/L,t=2.33,P〉0.05;（39.44±12.14） ng/L,t=0.91,P〉0.05].Conclusion MSCs has a protective effect on VILI by attenuating the degree of lung tissue injury,PMN lung infiltration and production of local pro-inflammatory cytokines.