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Objective: Diabetes (diabetes mellitus, DM) is caused by a variety of factors, systemic metabolic disorder characterized by chronic hyperglycemia, can lead to a clinical syndrome of the body multiple organ system damage. With the deepening of the DM Complications DM lung damage has received increasing attention. Recent studies have confirmed DM lung damage DM is also part of the systemic multi-system disease, DM may significantly increase the risk of pulmonary fibrosis. Transforming growth factor β1 (transforming growth factor beta1, TGF-β1) the fibrogenic cytokines play an important role in a variety of organ fibrosis process. c-Jun N-terminal kinase (c-Jun NH2-terminal kinases JNK) signaling pathway TGF-β1 downstream signal transduction pathways, abnormal expression of JNK may affect the activity of TGF-β1, thereby changing the process of fibrosis. Recent study found that, JNK over-activation is closely related with the DM liver fibrosis as well as the non-DM pulmonary interstitial fibrosis, TGF-β1/JNK signal transduction pathway DM pulmonary fibrosis is still small. a-smooth muscle actin (a-smooth muscle actin, a-SMA) and type I collagen (collagen Ⅰ, COL Ⅰ) is TGF-β1/JNK signal transduction pathways downstream of two important indicators to measure pulmonary fibrosis. Rosiglitazone (rosiglitazone, RGT), peroxisome proliferator-activated receptor γ (peroxisome proliferator-activated receptorγ, PPARγ) synthetic ligand, RGT improve insulin sensitivity, lower blood sugar, but also has potential organ protection and anti-fibrosis. The study by the enzyme-linked immunosorbent assay (enzyme linked immunosorbent assay, ELISA) to observe the changes in spontaneous DM rat-OLETF rat lung tissue expression of TGF-β1, and the application of Western blotting (Western Blotting) observed phosphorylation of JNK ( phosphorylated c-Jun NH2-terminal kinases, p-JNK), a-SMA, COL Ⅰ expression changes, explore TGF-β1/JNK whether the signaling pathways for DM pathogenesis of pulmonary fibrosis, one and set up the the RGT intervention group, observed changes in these indicators to explore the RGT whether DM pulmonary fibrosis have a protective effect. Method: 4-week-old OLETF rats 30 and its fellow non-DM control eight LETO rats, mice, in the absence of specific pathogen-caged, fed on standard diet. Rats once every 4 weeks oral glucose tolerance test (oral glucose tolerance test, OGTT). Into a mold OLETF rats 16 to 30 weeks, a total of eight randomly divided into the 8 model group (DM) and RGT intervention group and LETO rats were used as a control group (N). The RGT group RGT3mg/kg dose gavage, DM group N group to distilled water orally, were administered orally for 12 weeks, twice a day. 42 weeks, the rats were sacrificed and specimens from lung tissue, part was fixed in 10% neutral formalin, part placed in liquid nitrogen fixed -80 ° C low temperature refrigerator save follows: ① HE staining under light microscope structural changes of lung tissue: ② Masson staining of lung tissue collagen deposition; ③ measured by ELISA TGF-β1 expression in the lung tissue of rats in each group, and 450nm wavelength microplate reader measured the corresponding protein concentration; the ④ applications Western Blotting p-JNK semi-quantitative analysis of lung tissue in rats, a-SMA, COL I protein expression; gel image processing system, and β-actin or GAPDH as an internal reference to the corresponding protein bar with B-actin or GAPDH The ratio calculated the relative expression level of the protein. Results: ① HE staining showed: N lung tissue structure was normal: DM group rat lung tissue structural disorder, bronchial wall thickening, widening of the alveolar septa, part of the alveolar cavity atrophy, collapse, increased pulmonary interstitial and inflammation cell infiltration in: RGT rats lung tissue lesions compared with DM group reduced, but the structure of the lung tissue is not returned to normal. The ② Masson staining showed: the N rats alveolar septa, bronchioles, the small blood vessels around only a small amount of collagen fibers; increased DM lung interstitial collagen fibers arranged in disorder; the RGT lung interstitial collagen deposition than DM group to reduce, but still did not recover to normal. (3) lung tissue are of TGF-β1, p-JNK, a-SMA and COL I expression. Compared with N rats, DM rats lung tissue of TGF-β1, p-JNK, a-SMA and COL Ⅰ expression was significantly increased (P lt; 0.05), the difference was statistically significant: the RGT group and DM group phase The ratio of TGF-β1, p-JNK, a-SMA and COL I decreased expression (P lt; 0.05), the difference was statistically significant. Conclusion: ① OLETF rat lung tissue pathological structural changes, increased collagen deposition showing fibrosis trend, suggesting that the lungs are also a target organ of DM. The ② OLETF rat lung tissue TGF-β1, p-JNK, a-SMA and COL Ⅰ expression compared with LETO rats significantly increased, suggesting TGF-β1/JNK signal transduction pathway may be involved in the DM pulmonary fibrosis. ③ RGT OLETF rat lung tissue pathological changes after the intervention significantly reduced, reduced collagen deposition in the rat lung tissue TGF-β1, p-JNK, a-SMA and COL I expression was inhibited, suggesting that the RGT reduce DM lung fibrosis, may is achieved by interfering TGF-β1/JNK signal transduction pathway.
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