| Background:Infection,especially lung infection,is a common complication in cases of diabetes.The incidence of lung infection is higher than the average 3～4 times. With the increase of incidence of diabetes,the mortality of lung infection caused by diabetes is raised.As its exact pathogenesis hasn't been explained completely,it posed some difficulties to clinical intervention.In recent research,alveolar macrophageg which compose the first line of lung tissue decreased in producing cell factors and mediators of inflammation.There is an excess activation NF-κB of lung tissue against which PPAR-γagonist can act so that it can help inflammatory reaction and immune response with negative feedback regulating action.Therefore,studying about the effect of Pioglitazone on the level of alveolar macrophage IL-12,TNF-a and NF-κB of big mouse which suffer from diabetes to explore its protection mechanism in lung pathological changes has become a new direction to study diabetes lung pathological changes.Purpose:A mice suffering from diabete model will be established to study about the effect of Pioglitazone on the level of alveolar macrophage IL-12,TNF-a and NF-κB.Further investigations of protection mechanism in lung pathological changes will work to designate a new direction for researching on diabetes lung pathological changes.Methods:Streptozotocin(55mg/Kg) was injected into enterocelia to creat animal model of diabetes.Tirty-six healthy SD male rats were divided into three groups: normal control(NC) group,diabetes(DM) group and Pioglitazone(PIO) group.After eight weeks,the level of the blood glucose(BG) would be measured and ELISA was conducted to detect the level of TNF-a and IL-12 in the alveolar macrophages(AMs). After the tissue of left lung was taken out,the morphology of pathology was observed by optical microscope and expression of NF-κB was detected by immunohisto-chemistry. Then the right lung was taken out,the level of NF-κB mRNA and protein was detected by RT-PCR and Western-blot respectively.Result:The concentration of blood glucose in DM and PIO groups increased significantly compared with NC group(P＜0.001),but no statistical difference was found between DM and PIO group(P＞0.05).Compared with NC group,the level of the AMs cultivation supernatant of rates in TNF-a was significant increased in DM group(P＜0.001).The level of the AMs cultivation supernatant of rates in IL-12 of DM group was decreased significantly compared with NC group(P＜0.001),and there was no difference between PIO and DM group in AMs IL-12(P＞0.05).Compared with the NC group,expression of the lung tissues in NF-κB increased significantly in DM group(P＜0.001),but decreased obviously in PIO group.Testing the protein contents by western-blot showed that the widen of rates bands in DM group was deeper than NC group,but the bands in PIO group was between DM group and NC group. Compared with the NC group,expression of NF-κB mRNA and it's protein increased in DM group(P＜0.001);Compared with the DM group expression of NF-κB mRNA and it's protein decreased obviously in PIO group(P＜0.05).The basilar membranes of the alveolar epithelial cells and capillary endothelial cells in the lung tissues of diabetes rats were obviously thickened and the intervals of alveolus were widened,and the contents of the collagen and elastic protein in interstice were increased.And part of the alveolar space atrophy and almost collapse.Pioglitazone could reduce above injury.Conclusion:One reason of the reduced immune defence is that the alveolar macrophage of diabetes rats gives off less IL-12 and.The NF-κB is too active in the diabetes rats.The pioglitazone,as PPAR-γagonist,can defend NF-κB overactive through activating the PPAR-γto adjust inflammatory response and immune response negatively,reduce the expression of TNF-a and reduce the injury of lungs which defends the lungs,and not depend on hypoglycemia.
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