| Objective:Diabetes mellitus (diabetes mellitus, DM) is a chronic metabolic disorders, persistent high blood glucose can lead to a number of tissues and organs of metabolic abnormalities, functional disorders and structural change, study confirms diabetes lung damage is also a part of diabetes systemic diseases, diabetes can significantly increase the risk of pulmonary fibrosis. TGF-β1 is a profibrotic cytokine, play an important role in the process in a variety of organ fibrosis. JNK signaling pathway is an important downstream of TGF-β1, JNK may effect the abnormal expression of TGF-β1 activity, thereby changing the fibrosis process. Recent studies have found that, excessive activation of JNK is closely related to diabetes nephropathy and non-diabetes pulmonary fibrosis, while research on the relationship between TGF-β1/JNK signal transduction pathway and DM pulmonary fibrosis is little. Rosiglitazone is a synthetic ligand of peroxisome proliferator-activated receptor-γ(PPAR-γ). PPAR-γis capable of regulating metabolism, anti-inflammatory and anti-fibrosis. This study using immunohistochemistry to observe the changes of TGF-β1, phosphorylated JNK (p-JNK), fibronectin (FN), and typeⅢcollagen in OLETF rat lung, and to explore whether TGF-β1/JNK signaling pathways is important to the pathogenesis of diabetes pulmonary fibrosis. Establishing a rosiglitazone intervention group to observe the changes of these indicators, so that to explore whether rosiglitazone has a protective effect on diabetes pulmonary fibrosis.Methods:30 OLETF rats and 8 LETO rats which were 4 weeks old were reared in single cage with standard feed in specific pathogen-free conditions.They were taken OGTT on a regular basis. To age of 30 weeks,there were 16 OLETF rats modelled successfully.Dividing them into 2 groups randomly:DM group and the rosiglitazone (RGT) intervention group,8 LETO rats were normal (N) group.The RGT group was administered with rosiglitazone (3 mg/kg) by gavage daily.DM group and N group were administered with distilled water equal daily for 12 weeks. After 12 weeks, the rats were sacrificed, and the lung were obtained and fixated with 10% formalin:①Observed the morphological changes of the lung by HE staining;②Observed collagen deposition in lung tissue of each group by Masson staining;③Positioning TGF-β1, p-JNK, FN and typeⅢcollagen by immunohistochemistry, then evaluate the intensity of positive expression of TGF-β1 and p-JNK based on the percentage of stained cells and staining level, and determined mean optical density and the ratio of positive area and total area of FN and typeⅢcollagen by the image analysis system.Results:①HE staining:N group had normal alveolar structure. The lung organizational structure of DM group disordered, bronchial walll thickening, alveolar septum showed widened, part of alveolar atrophy and collapse, pulmonary interstitial increased, and there were inflammatory cell infiltration. Lung damages in RGT group were slighter than DM group, but it didn't recover to normal either.②Masson staining: Alveolar septum, peribronchial and perivascular of N group had little collagen fibers and in DM group they increased and disordered. Collagen deposition in RGT group was slighter than DM group, but still heavier than N group.③Immunohistochemistry: TGF-β1 could be seen in the cytoplasm of bronchial epithelial cells, typeⅡpneumocytes, vascular endothelium cells, alveolar macrophages and myofibroblasts. p-JNK distributed mainly in the cytoplasm and nucles of alveolar epithelial cells, bronchial epithelial cells, smooth muscle cells, vascular endothelial cells, macrophages, and infiltration of inflammatory cells. FN and typeⅢcollagen mainly scattered in the connective tissue column of small bronchial and vascular. Compared with the N group and RGT group, the DM group TGF-β1, p-JNK, FN and typeⅢcollagen expression increased (P<0.01), the difference was statistically significant.Conclusions:①Pathological changes and collagen fibers deposition occured in lung of OLETF rats, indicating that lung was another target organ of diabetes.②Compared with LETO rats, OLETF rats lung TGF-β1, p-JNK, FN and typeⅢcollagen expression increased, suggesting that TGF-β1/JNK signal transduction pathway may play a role in the pathogenesis of DM pulmonary damage.③After the intervention with rosiglitazone, the OLETF rats lung tissue TGF-β1, p-JNK, FN and typeⅢcollagen expression decreased, suggesting that rosiglitazone can improve DM pulmonary fibrosis probably by regulating TGF-β1/JNK signal pathway.
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