间充质干细胞缓解大鼠急性肺损伤的分子机制

发布时间：2018-10-18 18:41

【摘要】：目的探讨间充质干细胞(MSCs)抑制核因子(NF)-κB的活性和抑制亲环素(Cy P)A的表达而缓解急性肺损伤(ALI)的分子机制。方法首先比较脐带和骨髓MSCs的细胞形态、细胞表型、分化能力和免疫能力,并采用全基因组表达芯片比较两者的功能基因表达差异。通过注射脂多糖(LPS)制备SD大鼠ALI模型,研究输注MSCs能否通过抑制Cy PA的表达和抑制NF-κB的活性,进而控制炎症反应的过度激活和抑制氧化应激等,减轻内毒素所致的ALI。结果 CD29在脐带MSCs的阳性表达率低于在骨髓MSCs中的表达率(P0.01)。聚类分析发现骨髓来源的MSCs中高表达的基因主要集中在免疫相关和骨骼发育相关的基因,而脐带MSCs中高表达的基因主要集中在细胞分化、器官发育和信号转导的相关基因。对SD大鼠ALI损伤模型的研究发现,MSCs干预可减轻LPS对肺组织的损伤程度。LPS组各时间点血浆促炎因子巨噬细胞炎症蛋白(MIP)-2水平显著高于对照组和MSCs+LPS组(P0.05)。MSCs可显著抑制LPS诱发的炎症因子MIP-2的增高(P0.05)。与对照组相比,LPS组在各时间点Cy PA蛋白表达和TNF-α表达水平均显著升高(P0.05),而MSCs可以抑制Cy PA的蛋白和TNF-α的表达(P0.05)。肺组织NF-κB在LPS组增高,MSC干预可有效降低NF-κB表达(P均0.05)。LPS组肺组织丙二醛(MDA)和髓过氧化物酶(MPO)活性水平在三个时间点均明显高于对照组,在各相应时间点,MSCs+LPS组肺组织MDA和MPO均明显低于LPS组(P均0.05)。结论脐带MSCs明显降低了大鼠血浆促炎因子的水平,可显著抑制Cy PA的表达,并通过抑制NF-κB的活性减轻了LPS引起的全身炎症反应和氧化应激,减轻了LPS所致的肺损伤。
[Abstract]:Objective to investigate the molecular mechanism of mesenchymal stem cell (MSCs) inhibiting the activity of nuclear factor (NF)-魏 B and the expression of cyclophile (Cy P) A to alleviate acute lung injury (ALI). Methods the cell morphology, cell phenotype, differentiation ability and immune ability of cord and bone marrow MSCs were compared first, and the difference of functional gene expression between them was compared by using the whole genome expression chip. The ALI model of SD rats was established by injection of lipopolysaccharide (LPS) to study whether the infusion of MSCs could inhibit the expression of Cy PA and the activity of NF- 魏 B, and then control the excessive activation of inflammatory reaction and inhibit oxidative stress, so as to alleviate the ALI. induced by endotoxin. Results the positive expression rate of CD29 in umbilical cord MSCs was lower than that in bone marrow MSCs (P0.01). Cluster analysis showed that the highly expressed genes in MSCs from bone marrow were mainly related to immune and bone development, while those in MSCs of umbilical cord were mainly related to cell differentiation, organ development and signal transduction. The study of ALI injury model in SD rats showed that MSCs intervention could reduce the degree of lung injury caused by LPS. The level of (MIP) 2 in plasma pro-inflammatory factor macrophages in LPS group was significantly higher than that in control group and MSCs LPS group (P0.05). MSCs significantly inhibited the level of (MIP) 2). The increase of MIP-2 induced by LPS (P0.05). Compared with the control group, the expression of Cy PA protein and TNF- 伪 in LPS group were significantly increased at each time point (P0.05), while MSCs could inhibit the expression of Cy PA protein and TNF- 伪 (P0.05). NF- 魏 B in lung tissue was increased in LPS group. MSC intervention could effectively decrease the expression of NF- 魏 B (P 0.05). The levels of MDA (MDA) and myeloperoxidase (MPO) activity in lung tissue in). LPS group were significantly higher than those in control group at three time points. The lung tissue MDA and MPO in, MSCs LPS group were significantly lower than those in LPS group at each corresponding time point (P0. 05). Conclusion umbilical cord MSCs can significantly reduce the level of plasma pro-inflammatory factor and inhibit the expression of Cy PA in rat plasma. By inhibiting the activity of NF- 魏 B, the systemic inflammatory response and oxidative stress induced by LPS are alleviated, and the lung injury induced by LPS is alleviated.
【作者单位】：天津市第三中心医院心脏中心;北京军区总医院麻醉科;天津市胸科医院心内科;河北省巨鹿县医院麻醉科;
【基金】：2015年中国博士后科学基金资助项目(2015M581308) 天津市科学技术委员会重点项目(11ZCGYSY02000) 天津市卫生局重点攻关项目(12KG106)
【分类号】：R563

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