【摘要】：目的探討間充質(zhì)干細(xì)胞(MSCs)抑制核因子(NF)-κB的活性和抑制親環(huán)素(Cy P)A的表達(dá)而緩解急性肺損傷(ALI)的分子機(jī)制。方法首先比較臍帶和骨髓MSCs的細(xì)胞形態(tài)、細(xì)胞表型、分化能力和免疫能力,并采用全基因組表達(dá)芯片比較兩者的功能基因表達(dá)差異。通過注射脂多糖(LPS)制備SD大鼠ALI模型,研究輸注MSCs能否通過抑制Cy PA的表達(dá)和抑制NF-κB的活性,進(jìn)而控制炎癥反應(yīng)的過度激活和抑制氧化應(yīng)激等,減輕內(nèi)毒素所致的ALI。結(jié)果 CD29在臍帶MSCs的陽性表達(dá)率低于在骨髓MSCs中的表達(dá)率(P0.01)。聚類分析發(fā)現(xiàn)骨髓來源的MSCs中高表達(dá)的基因主要集中在免疫相關(guān)和骨骼發(fā)育相關(guān)的基因,而臍帶MSCs中高表達(dá)的基因主要集中在細(xì)胞分化、器官發(fā)育和信號轉(zhuǎn)導(dǎo)的相關(guān)基因。對SD大鼠ALI損傷模型的研究發(fā)現(xiàn),MSCs干預(yù)可減輕LPS對肺組織的損傷程度。LPS組各時(shí)間點(diǎn)血漿促炎因子巨噬細(xì)胞炎癥蛋白(MIP)-2水平顯著高于對照組和MSCs+LPS組(P0.05)。MSCs可顯著抑制LPS誘發(fā)的炎癥因子MIP-2的增高(P0.05)。與對照組相比,LPS組在各時(shí)間點(diǎn)Cy PA蛋白表達(dá)和TNF-α表達(dá)水平均顯著升高(P0.05),而MSCs可以抑制Cy PA的蛋白和TNF-α的表達(dá)(P0.05)。肺組織NF-κB在LPS組增高,MSC干預(yù)可有效降低NF-κB表達(dá)(P均0.05)。LPS組肺組織丙二醛(MDA)和髓過氧化物酶(MPO)活性水平在三個(gè)時(shí)間點(diǎn)均明顯高于對照組,在各相應(yīng)時(shí)間點(diǎn),MSCs+LPS組肺組織MDA和MPO均明顯低于LPS組(P均0.05)。結(jié)論臍帶MSCs明顯降低了大鼠血漿促炎因子的水平,可顯著抑制Cy PA的表達(dá),并通過抑制NF-κB的活性減輕了LPS引起的全身炎癥反應(yīng)和氧化應(yīng)激,減輕了LPS所致的肺損傷。
[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- 偽 in LPS group were significantly increased at each time point (P0.05), while MSCs could inhibit the expression of Cy PA protein and TNF- 偽 (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.
【作者單位】： 天津市第三中心醫(yī)院心臟中心;北京軍區(qū)總醫(yī)院麻醉科;天津市胸科醫(yī)院心內(nèi)科;河北省巨鹿縣醫(yī)院麻醉科;
【基金】：2015年中國博士后科學(xué)基金資助項(xiàng)目(2015M581308) 天津市科學(xué)技術(shù)委員會(huì)重點(diǎn)項(xiàng)目(11ZCGYSY02000) 天津市衛(wèi)生局重點(diǎn)攻關(guān)項(xiàng)目(12KG106)
【分類號】：R563

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