| Objective: Diabetic lung damage is one of complications of diabetes mellitus (DM), that is confirmed by more and more study. The pathogenesis of diabetic lung damage is not clear at present. oxidative stress caused by DM is the critical mechanism resulting in development of the complication of DM. Domestic and international researches show that oxidative stress is involved and play an important role in the process. Advanced glycation end products (AGEs) are closed related to the occurrence and development of diabetic chronic complications. It can cause much more production of reactlve oxygen species (ROS) when AGEs interact with receptor of advanced glycation end products (RAGE) on Cell surface, leading to oxidative stress. In normal physiology and pathological situation, many enzymes take part in the production of ROS, and previous study have suggested that NADPH oxidase is a major source ROS produced in many nonphagocytic cells. Response to the stimulus of the specific factors such as cytokine, hyperglycemia, AGEs, lipidperoxides, and so on, NADPH oxidase can be activated to produce excessive ROS by oxidative burst, inducing tissue damage. Nuclear factor-kappa B (NF-κB) is a pleiotropic transcription factor widely existing in almost all cells. Under resting condition, NF-κB binding to inhibitor kappa B (IκB) exist in cytoplasm by inactive form. When cells are stimulated by oxygen radical, cytokine, virus, and so on, NF-κB dissociates from IκB and enter cell, that NF-κB bind to specific sequences to regulate the expression of appropriate genes. Cordyceps sinensis (BerK.)Sacc is beneficial to lung and kidney, improving fragile condition, and supplementing Qi. The trace element of Cordyceps sinensis (BerK.)Sacc can be the coenzemy of glutathione peroxidase (GSH-PX) and other enzymes, improving the activity of enzymes, and have the effect of antioxidation. Rosiglitazone is one of thiazolidinediones (TZDs), which is an effective agonist of the transcription factor peroxisome proliferators-activated receptor-gamma (PPARγ), and have many functions, including regulating glucose and lipid metabolism, lowering blood pressure, anti-inflammation, antiproliferative and antioxidative. In this study, rat model of type 1 diabetes was set up by intraperitoneal injection of streptozocin (STZ). Cordyceps sinensis cultivated by aretificial fermentation and rosiglitazone were applied for intervention. The expression of AGEs, NF-κB and NADPH oxidase in the rat lung tissue was detected through the methods of patomorphism and molecular biology to explore the effect of AGEs, NF-κB and NADPH oxidase in the genesis and development of diabetic lung damage, and explore the protective effect of Cordyceps sinensis cultivated by aretificial fermentation and rosiglitazone.Method: 60 eight weeks male SD rats were divided into two groups randomly: 15 normal contral rats (group A) and 45 test rats. Test rats were injected intraperitoneally with STZ (55mg/kg). 72 hours later, the rats whose blood glucose levels were higher than 16.7mmol/L in the subsequent 3 days were considered as diabetic rats. They were randomly divided into three groups: diabetic model rats (group B), diabetic rats treated with 2.4g/kg/d Cordyceps sinensis cultivated by artificial fermentation (group C) and diabetic rats treated with 4mg/kg/d rosiglitazone (group D). The experiment lasted 12 weeks. Blood glucose and body weight were measured at the beginning of the experiment and at the end of 0 weeks, 4 weeks, 8 weeks, 12 weeks respectively. Rats were sacrificed by fermoral artery bloodletting after 12 weeks, and both lungs were removed. Right lungs were prepared for H.E stain to observe the changes of lung morphous. The level and location of protein expression about AGEs and NF-κB were examined by immunohistochemistry. The expression of NF-κB mRNA and p22phox mRNA in left lungs were analysed with reverse transcription polymerase chain reaction (RT-PCR). All the experimental data were dealt with SPSS13.0. If variable were consistent with homogeneity of variance, analysis of variance (ANOVA) was used to compare multi-group variables, LSD test was used to comprare inter-group variable.Results:1 At the end of 4 weeks, 8 weeks and 12weeks, The blood glucose in group B, C and D were significantly higher than group A (all p<0.01). The body weight in group B, C and D were significantly higher than group A (all p<0.01). There was no significant difference in body weight and blood glucose of group B, C and D (p>0.05).2 H.E stain showed that compared with group A, In group B alveolar structure was destroyed, and alveolar space became shrunken, even atrophic. there was infiltration of inflammatory cells. capillary of alveola became narrowed, even occlusive. There were some improvements in group C and D compared with group B.3 Immunohistochemistry showed that compared with group A, the positive expression of AGEs and NF-κB in group B were significantly increased (all p<0.01). there is the obvious activity of AGEs and NF-κB in lung bronchiolar epithelium mucosae, alveolar epithelial cells and lung interstitial. And the deep yellow stainings were seen in nucleus and kytoplasm. The expression of AGEs and NF-κB in rat lung in group C and D decreased compared with group B (all p<0.01).4 Reverse transcription polymerase chain reaction (RT-PCR) results showed that compared with A group, the expression of NF-κB mRNA and p22phox mRNA in B, C, D group were significantly increased (all p<0.01). the expression of both were decreased in C and D group (all p<0.01).Conclusion:1 The rats were intrapenitoneally injected a high-dose STZ to destroyβcells of pancreas islet and lead to an absolute lake of insulin secretion, by which the rat model was set up. The model which was characterized by significantly diabetes symptoms, such as continuous hyperglycemia, weight reduction, hyperglycemia, is similar to the clinical characteristic of type 1 diabetes. 2 There was pathomorphologic changes in lung tissue of diabetes rats, and it showed lung was a target organ in DM. The expression of AGEs, NF-κB and p22phox in diabetic model rats were signifiacantly higher than normal contral group, which shown that there may be an interaction among the three factors, and the changes of expression were closely related to the the genesis and development of diabetic lung damage.3 After treated by Cordyceps sinensis cultivated by aretificial fermentation and rosiglitazone, the expression of AGEs, NF-κB and p22phox was decreased in rats lung, and changes of lung pathologic were improved obviously. The results showed that both could regulate genes by the way of antioxidation and anti-inflammatory to play a pretective effect to lung tissue.
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