Zhou M I, Chen Dong-Ling, Jiang Tao, Feng Yan-Mei, Han Xiao-Li
Department of Respiratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400042, P.R. China.
Exp Ther Med. 2015 Nov;10(5):1857-1864. doi: 10.3892/etm.2015.2715. Epub 2015 Sep 1.
The aim of the present study was to investigate the effects of bone marrow-derived mesenchymal stem cells (BMSCs) transfected with survivin on lung fibrosis in mice. Mice with bleomycin-induced pulmonary fibrosis were allocated at random to group A, B or C, and injected with 1×10 survivin gene-expressing BMSCs, 1×10 BMSCs or normal saline, respectively. A total of 6 mice were sacrificed from each group on days 7, 14 and 28 after treatment. The extent of alveolitis and pulmonary fibrosis was assessed and the apoptotic rates of the BMSCs and survivin-expressing BMSCs were detected. The content of surfactant protein A (SP-A) in the lung and hydroxyproline (Hyp) in the serum was measured. The mRNA expression levels of transforming growth factor (TGF)-β1 and matrix metalloproteinase (MMP)-9 in the lung tissue of the mice was detected. Furthermore, the protein expression levels of caspase-3 and -9 were detected. The apoptotic rates of the BMSCs (group B) and survivin-expressing BMSCs (group A) were 14.466±1.953 and 7.718±0.493%, respectively. The degree of lung fibrosis in groups A and B was reduced compared with that in group C. The hydroxyproline content in groups A and B was reduced compared with that in group C, and the SP-A content in groups A and B was increased compared with that in group C. The mRNA expression levels of TGF-β1 in group A were reduced compared with those in group B, and the levels in group B were reduced compared with those in group C. By contrast, the mRNA expression levels of MMP-9 in group A were increased compared with those in groups B and C, and the levels in group B were increased compared with those in group A. The expression levels of caspase-3 and -9 in group A were elevated compared with those in groups B and C. In conclusion, BMSCs are effective in preventing bleomycin-induced lung fibrosis, and survivin may enhance the protective effects of BMSCs.
本研究的目的是探讨转染生存素的骨髓间充质干细胞（BMSCs）对小鼠肺纤维化的影响。将博来霉素诱导的肺纤维化小鼠随机分为A、B、C组，分别注射1×10个表达生存素基因的BMSCs、1×10个BMSCs或生理盐水。治疗后第7、14和28天，每组处死6只小鼠。评估肺泡炎和肺纤维化程度，检测BMSCs和表达生存素的BMSCs的凋亡率。测定肺组织中表面活性蛋白A（SP-A）含量和血清中羟脯氨酸（Hyp）含量。检测小鼠肺组织中转化生长因子（TGF）-β1和基质金属蛋白酶（MMP）-9的mRNA表达水平。此外，检测半胱天冬酶-3和-9的蛋白表达水平。BMSCs组（B组）和表达生存素的BMSCs组（A组）的凋亡率分别为14.466±1.953%和7.718±0.493%。与C组相比，A组和B组的肺纤维化程度减轻。与C组相比，A组和B组的羟脯氨酸含量降低，与C组相比，A组和B组的SP-A含量升高。与B组相比，A组TGF-β1的mRNA表达水平降低，与C组相比，B组水平降低。相比之下，与B组和C组相比，A组MMP-9的mRNA表达水平升高，与A组相比，B组水平升高。与B组和C组相比，A组半胱天冬酶-3和-9的表达水平升高。总之，BMSCs可有效预防博来霉素诱导的肺纤维化，生存素可能增强BMSCs的保护作用。
