摘要
目的探讨骨髓间充质干细胞(MSC)对失血性休克后急性肺损伤(ALI)大鼠的治疗作用及机制。方法以雄性Wistar大鼠作为供体提取MSC。将36只雄性Wistar大鼠通过气管内注射细菌脂多糖建立大鼠ALI模型,并将其中18只大鼠通过静脉注射MSC予以治疗(MSC组),余18只为ALI组,同时以8只健康Wistar大鼠作为对照组。其中ALI组及MSC组各取10只大鼠用于大鼠生存时间比较,另每组8只与对照组大鼠进行肺湿/干重比、肺泡灌洗液中肿瘤坏死因子α(TNF-α)、转化生长因子β1(TGF-β1)、Claudin-4含量监测,并通过Western blotting及逆转录聚合酶链反应(RT-PCR)方法检测肺组织中Claudin-4蛋白及mRNA表达变化。结果 ALI组和MSC组中大鼠的48 h生存情况比较差异具有统计学意义(χ2=5.05,P<0.05)。ALI组和MSC组大鼠肺组织的湿/干重比及TNF-α较对照组均明显增加,且ALI组大鼠增高更为明显(P均<0.05);而对照组及MSC组大鼠的TGF-β1及Claudin-4水平较明显高于ALI组,且MSC组更为显著(P均<0.05)。RT-PCR结果显示对照组大鼠Claudin-4 mRNA水平高于ALI组,但是明显低于MSC组(P均<0.05),与Western blotting结果检测结果一致。结论 MSC治疗通过上调肺组织中Claudin-4的表达可以减轻大鼠失血性休克后ALI。
Objective To investigate the effects of mesenchymal stem cell （MSC） treatment in acute lung injury （ALI） induced by hemorrhagic shock in rats. Methods Using male Wistar rats as donors to obtain MSC. Total of 36 male Wistar rats were randomly divided into the ALI and MSC groups, 18 in each group, and the healthy male Wistar rats served as control group. The ALI model was reproduced by intratracheal injection of lipopolysaceharide in a dose of 5 mg/kg in the ALl and MSC groups, and the rats in the MSC group injected MSC through the penile dorsal vein additionally. Rat survival time was compared in the ALI and MSC groups. The lung wet/dry ratio, tumor necrosis factor-or （TNF-α）, transforming growth factor-β1 （TGF-β1） and Claudin-4 were recorded and compared among the three groups, and the expression of Claudin-4 protein and mRNA were detected by Western blotting and reversetranscription polymerase chain reaction （RT-PCR）, respectively. Results The rats survival situation in the MSC group was better than that in the ALl group （X^2 = 5.05, P〈 0.05）. The lung wet/ dry ratio and TNF-α in the ALl and MSC groups were higher than those in the control group, and were highest in the ALl group （allP〈0.05）. The levels of TGF-β1 and Claudin-4 in the control and MSC groups increased obviously as compared with those in the ALl group, and it increased most in the MSC group （all P〈0.05）. Furthermore, the expressions of Claudin-4 mRNA and protein in the control group were all higher than those in the ALl group, and were much lower than those in the MSC group （all P 〈 0.05）. Conclusion MSC could alleviate ALl induced by hemorrhagic shock in rats by upregulating the expression of Claudin-4 in the lungs.
出处
《中华危重症医学杂志（电子版）》
CAS
2014年第1期25-29,共5页
Chinese Journal of Critical Care Medicine:Electronic Edition
基金
浙江省科技厅计划项目(2013C33202)
浙江省医药卫生科技计划一般项目(2012KYB012)
浙江省中医药科学研究基金计划(2012ZA018)
关键词
间质干细胞
休克
出血性
急性肺损伤
大鼠
Mesenchymal stem cell
Shock, hemorrhagic
acute lung injury
Rats
