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NF-κB反义寡核苷酸对博来霉素损伤小鼠肺组织中肺成纤维细胞转分化的影响。

The effect of NF-κB antisense oligonucleotide on transdifferentiation of fibroblast in lung tissue of mice injured by bleomycin.

作者信息

Zhou Yan, Zhang Xiaoye, Tan Mingqi, Zheng Rui, Zhao Li

机构信息

Department of Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Mol Biol Rep. 2014 Jun;41(6):4043-51. doi: 10.1007/s11033-014-3273-8. Epub 2014 Mar 2.

Abstract

To investigate the influence of NF-κB antisense oligonucleotide on transdifferentiation of fibroblast in the pathological process of bleomycin-induced pulmonary fibrosis in mice. 6 h before molding of C57BL/6 model of pulmonary fibrosis in mice, NF-κB antisense oligonucleotide was injected from caudal vein. Then the lung tissue was collected for primary culture as well as model group and control group. Cultured cells were used for immunocytochemical staining of p65, IκB-α and α-SMA proteins as well as in situ hybridization staining of p65 and IκB-α. Then image analysis was carried out. The expressions of all the indicators were expressed as mean optical density. Compared with the control group, the expressions of p65 protein, IκB-α protein and α-SMA protein of model group were increased, as well as the expressions of p65 mRNA and IκB-α mRNA (P < 0.05). Compared with model group, the expressions of all indicators of intervention group were decreased (P < 0.05). P65 protein and p65 mRNA were positively correlated with the expression of α-SMA protein respectively. p65 protein and p65 mRNA were positively correlated with the expressions of IκB-α protein and IκB-α mRNA respectively. NF-κB antisense oligonucleotide can inhibit the transdifferentiation of fibroblast towards myofibroblast in the pathological process of bleomycin-induced pulmonary fibrosis in mice.

摘要

探讨核因子κB(NF-κB)反义寡核苷酸对博来霉素诱导的小鼠肺纤维化病理过程中肺成纤维细胞转分化的影响。在C57BL/6小鼠肺纤维化模型造模前6小时,经尾静脉注射NF-κB反义寡核苷酸。然后收集肺组织进行原代培养,并设立模型组和对照组。对培养的细胞进行p65、IκB-α和α-平滑肌肌动蛋白(α-SMA)蛋白的免疫细胞化学染色以及p65和IκB-α的原位杂交染色。随后进行图像分析。所有指标的表达均以平均光密度表示。与对照组比较,模型组p65蛋白、IκB-α蛋白和α-SMA蛋白的表达增加,p65 mRNA和IκB-α mRNA的表达也增加(P<0.05)。与模型组比较,干预组各指标表达均降低(P<0.05)。p65蛋白和p65 mRNA分别与α-SMA蛋白的表达呈正相关。p65蛋白和p65 mRNA分别与IκB-α蛋白和IκB-α mRNA的表达呈正相关。NF-κB反义寡核苷酸可抑制博来霉素诱导的小鼠肺纤维化病理过程中肺成纤维细胞向肌成纤维细胞的转分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e16d/4033808/904c0ee0a990/11033_2014_3273_Fig1_HTML.jpg

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