| Objective:In recent years, it has caused extensive concern that the lung may be another target organ of diabetes mellitus. Domestic and international researches confirm that the form of organization of the lungs have changed in the early stage of diabetes course, such as alveolar epithelial cells, capillary endothelial cells and pulmonary interstitial collagen fibers proliferation. Then pulmonary ventilation function and diffusion function can be affected and further developed to pulmonary interstitial fibrosis. Recent studies showed that immune and inflammation play important roles in the initiation and development of diabetes. Nuclear factor kappa B (NF-κB), transforming growth factor-β1(TGF-β1) and c-Jun N-terminal Kinase (JNK) are all important inflammatory facters and the recent researches suggested the abnormal expression of NF-κB, TGF-β1and JNK may be associated with pulmonary fibrosis. Cordyceps sinensis (Berk.) Sacc is a kind of Chinese unique valuable and traditional herb. It is confirmed that Cordyceps sinensis (Berk.)Sacc has an effect on reinforcing the function of kidneys and lungs. Previous studies found that CS has certain therapeutic effects on lung injuries caused by diabetes, but the exact mechanism remains not clear. In this study, Cordyceps sinensis cultivated by artificial fermentation and Pioglitazone were applied to the diabetic rats. The expression of NF-κB, TGF-β1and JNK of the lung tissue were detected by the use of pathological morphology and molecular biology. Our aim was to assess the potential relationship between the NF-κB, TGF-β1and JNK with the occurrence and development of diabetes lung injuries, and investigate the lung protective mechanism of artificial Cordyceps sinensis.Methods:90eight-week male SD rats were divided into two groups randomly:10normal control rats and80experimental rats. The DM rat models were made by intravenous injection of STZ(45mg/kg).Then they were randomly assigned into six groups, including control group (group N), diabetes group (group D), small-dose CS group (group L,0.6g/kg-d), medium-dose CS group (group M,2.5g/kg-d), large-dose CS group(group H,5g/kg-d), PIO treatment group(group P,4mg/kg-d). After modeling successfully for eight weeks, total cholesterol and triglyceride were tested. The morphologic change of lung was observed under light microscopy, and the expressions of NF-κB, TGF-β1protein and NF-κB, TGF-β1, JNK mRNA were detected by immunohistochemistry and reverse transcription-polymerase chain reaction. Results:1. The DM rat model was established successfully.2. At the end of the test, the level of TC and TG in each CS group was significantly lower than that in group D (P<0.05), which were significantly higher than that of the control group (P<0.05).3. Hematoxylin and eosin staining showed that, compared with control group, the changes of pulmonary pathology in group D were structure disturbance of lung tissue including bullae of lung, alveolar atrophy and collapse, widening of alveolar septum, increase and disorder of collagenous fiber even with the pulmonary fibrosis trend, and mass infiltration of inflammatory cells. Compared with D group, the above changes in group CS treatment and group P were decreased in some degree. The effects in group H and P were better than those of group L or M.4. Immunohistochemistry showed that, the expressions of NF-κB and TGF-β1were obviously decreased differing in degree in group P and group CS treatment than that of group D, which were remarkably increased compared with group N. And the expressions above were significantly lower in group H and P than that of group L and M.5. RT-PCR reaction showed that the expressions of NF-κB, TGF-(31and JNK mRNA in group P or group CS treatment were lower than that of group D(P<0.05), which were remarkably higher than that of group N (P<0.05). And the expressions above in group H and P were significantly lower than that of group L and M (P<0.05).Conclusions:1. There were the pathological morphological changes in the lung tissue of STZ-induced DM rats, which prompted that the lung was one of target organs of diabetes mellitus.2. In diabetic rats, the expressions of NF-κB, TGF-β1and JNK were remarkably increased, and the interaction of them may improve the progress of diabetic pulmonary fibrosis.3. The expressions of NF-κB, TGF-β1and JNK mRNA decreased significantly after the treatment of artificial cordyceps sinensis cultivated, while the pathological changes of lung tissue improved significantly. CS may confront pulmonary fibrosis by inhibiting NF-KB-mediated inflammation and oxidative stress to inhibit TGF-β1/JNK signal path. |
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