ObjectiveTo investigate the role of myeloid-derived suppressor cell (MDSC) in bleomycin (BLM)-induced pulmonary fibrosis and the possible mechanism of bone marrow mesenchymal stem cell (MSC) in therapy of BLM-induced pulmonary fibrosis.MethodsBone marrow mesenchymal stem cells (MSC) were harvested from 6-week old male BALB/c mice. One hundred and four female BALB/c mice were randomly divided into 3 groups. Mice in control (n=32) and BLM group were instilled with normal saline (NS) or BLM via trachea and NS were injected via tail vein on the 1st, 2nd and 3rd day after NS administration. Mice in MSC group (n=40) were instilled with BLM via trachea and MSC (total cell number=1.5×106) were injected via tail vein. On the 1st, 3rd, 5th, 8th, 11th, 14th, 18th, 21st, 25th and 32nd day after BLM administration, the percentage of Gr-1+CD11b+ cells in peripheral blood mononuclear cell (PBMC) was detected by flow cytometry. Eight mice from each group were killed on the 3rd, 8th, 18th and 32nd day after BLM administration, the percentage of Gr-1+CD11b+ cells in the lung tissue was detected by flow cytometry. Meanwhile, the lung tissue specimens were stained with Masson. The sry gene of Y chromosome was detected by polymerase chain reaction (PCR).ResultsCompared with BLM group, MSC transplantation significantly reduced pulmonary inflammation in MSC group [(1.32±0.25) vs. (2.53±0.56); and (1.06±0.42) vs. (2.27±0.82), respectively, P<0.01)]. Likewise, MSC transplantation significantly reduced pulmonary fibrosis and deposition of collagen as compared with BLM group [(1.02±0.44) vs. (1.81±0.74), and (1.51±0.73) vs. (2.72±0.54), respectively, P<0.05)]. The percentage of Gr-1+CD11b+ cells in the BLM group was significantly increased as compared with control group. Compared with BLM group, MSC transplantation significantly reduced Gr-1+CD11b+ cells in MSC group (P<0.05). The sry gene (201 bp) was detected in the lungs of female mice within 96 hours after MSC administration.ConclusionsMDSC participates in the procedure of BLM-induced pulmonary fibrosis. Syngeneic MSC inhibits the generation of MDSC and further suppresses BLM-induced pulmonary fibrosis.
ObjectiveTo investigate the effects of smoking combined with intermittent hypoxia on the pathophysiology of lung tissue and thoracic aorta, and the endothelial injury.MethodsTwenty-four rats (SPF, female, six weeks old) were divided randomly into 4 groups (n=6). The control group was given false smoking and normal oxygen exposure, the smoking-exposed group was exposed in smoking, the intermittent hypoxia group was exposed in intermittent hypoxia environment, and the overlap group was exposed to smoking and intermittent hypoxia. After 8 weeks, body weight, right ventricular hypertrophy index (RVHI), the pathological changes of lung tissue and thoracic aorta were measured, and the level of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α) in serum of rats were evaluated.ResultsRVHI of rats in the smoking-exposed group, intermittent hypoxia group, overlap group were higher than that in the control group. In addition, RVHI in the overlap group was higher than that in the smoking-exposed group, intermittent hypoxia group (all P<0.05). The levels of ET-1, VEGF and SDF-1α in the serum of the smoking-exposed group, intermittent hypoxia group and overlap group were higher than those in the control group, while the level of eNOS was lower than that in the control group, (all P<0.05), the most significant difference was between control group and the overlap group. Pathological observation of lung tissue and thoracic aorta showed obvious emphysema in the smoking-exposed group and overlap group, which was more obvious in the overlap group than that in the smoking-exposed group (all P<0.05). Lung interstitial inflammatory infiltration, bronchial wall lymphocyte hyperplasia and pulmonary fibrosis were shown in different degrees in the smoking-exposed group, intermittent hypoxia group and overlap group, and the pulmonary arteriole wall showed thickening, fibrosis and peripheral inflammatory infiltration also were found in these groups. Thoracic aorta in the smoking-exposed group, intermittent hypoxia group and overlap group showed different degrees of endothelial cell injury, middle membrane thickening, and collagen fiber hyperplasia. The pathological features of the overlap group were most obvious compared to the other two groups.ConclusionsSmoking and intermittent hypoxia exposure can lead to different degrees of lung tissue and vascular endothelial injury and decrease of vascular endothelial protective factors in rats, resulting in dysfunction of vascular endothelial cells, which leads to the structural remodeling of pulmonary arterioles and aorta, such as thickening, fibrosis, etc. Combined smoking and intermittent hypoxia exposure can lead to more serious pathological damage.