Difference And Significance Of STAT In Rats Model With Chroinc Bronchitis And Bronchial Asthma

Objective : To explore the difference and expression of signal transducers and activators of transcription (STAT)4 and STAT6 in lung tissue from rats model with chronic bronchitis (CB) and bronchial asthma (BA). To analyze the relationship between the expression of different STAT protein, Th1/Th2 imbalance and the airway mucus hypersecretion. And to study the effects of dexamethasone (DEX) on the process.Methods:30 SD masculine rats were randomly divided into 5 groups (the weight were about 130 to 200g.). The chronic bronchitis group (A group), the asthma group (B group), the chronic bronchitis+ dexamethasone group (C group), the asthma+ dexamethasone group (D group) and the control group (E group), each n=6. Lung tissue sections were stained with hematoxylin and eosin (H-E) for general morphology and alician blue-periodic acid schiff (AB-PAS) for identification of goblet cell. The pathologic changes were observed by ender optical microscope. The total and differentiated white blood cell counts of BALF were performed on different count fluids. The content of mucins (MUC) and the levels of cytokine interleukin (IL) -4 and interferon (IFN) -γproduction in the supernatants of BALF were determined by sandwich ELISA. And STAT4, STAT6 protein were detected with immunohistochemistry.Results: (1) Characteristic pathological manifestions of chronic brochitis were found in A group. The airway inflammation and Goblet cell hyperplasia (GCH) were significantly alleviated in C group. The change of bronchi epithelium and inflammatory cells infiltration below mucosa in B group were observed. GCH and mucus retarded in airway lumen in B group were also observed. The airway inflammation and GCH were significantly alleviated in DEX treated group. (2) STAT protein were found strongly expressed in rat chronic bronchitis and asthma model, and the epithelial cells were the chief expressing cells. (3) The STAT4 levels of A group (47.65±7.62) were statistically higher than that of the control group (25.57±4.38) (P <0.05). The STAT4 levels of B group (18.42±5.76) were significantly lower than that of the control group (P <0.01). The IFN-γlevels [(412.36±38.59)pg/ml, (167.56±15.79)pg/ml and (87.61±13.27)pg/ml respectively] changed as the same tendency. There was a significant correlation between the content of STAT4 and IFN-γlevel in A group (r=0.638, P <0.01). (4) The STAT6 levels of A group (6.58±2.48) were significantly lower that of the control group (13.43±2.06) (P <0.01). The STAT6 levels of B group (32.39±4.85) were statistically higher than that of the control group (P <0.01). The IL-4 levels [(42.76±8.96)pg/ml, (85.92±9.22)pg/ml and (285.65±92.43)pg/ml respectively] changed as the same tendency. There was a significant correlation between the content of STAT6 and IL-4 level in B group (r=0.762, P <0.01). (5) There was a significant correlation between the absolute numbers of neutrophils in BALF and the content of STAT4 in the epithelial cells of bronchus (r=0.549, P <0.01). And there was a significant correlation between the absolute numbers of EOS in BALF and the content of STAT6 in the epithelial cells of bronchus (r=0.874, P <0.01). (6) The level of IFN-γfrom C group (312.47±29.24pg/ml) were significantly lower than those from A group (412.36±38.59) (P <0.01), however the change of the levels of IL-4 were no significantly between C group and A group (51.02±11.58pg/ml and 42.76±8.96pg/ml) ( P >0.05 ) . The level of IL-4 from D group (112.26±15.47pg/ml) were significantly lower than those from B group (285.65±92.43) (P <0.01), however the change of the levels of IFN-γwere no significantly between D group and B group (98.45±12.32pg/ml and 87.61±13.27pg/ml) (P>0.05). (7) The content of MUC from C group (2.26±1.37) and D group (1.38±0.94) were significantly lower than A and B group (4.74±1.39 and 3.66±1.72) respectively (P <0.01). Mucins from all groups were higher than those from E group (0.51±0.10). (8) There was a significant correlation between the content of STAT4 and MUC in A group and the same correlation between the content of STAT6 and MUC in B group (r=0.517; r=0.645, P <0.01).Conclusions:(1) It have shown enhanced immmunoreactivity for STAT4 and STAT6 in the airway of chronic bronchitis and bronchial asthma rat model respectively. And epithelial cells were the chief expressing cells. (2) The obvious immune response difference was found in CB and BA. STAT4 was contribute to BA and STAT6 may to CB. (3) The T helper lymphocytes-1 (Th1) which secrets IFN-γis predominant T-lymphocyte, the scale of Th1/Th2 is abnormity in chronic bronchitis pleural effusion, but dexamethasone play an important role in decreasing the level of STAT4,IFN-γand intervening in excursion of the Th1/Th2. (4) But the T helper lymphocytes-2 (Th2) which secrets IL-4 is predominant T-lymphocyte in bronchial asthma rat model. Dexamethasone also had an inhibitory effect on the expression of STAT6. (5) It have shown that STAT4 and STAT6 may be a key process in modulatory mechanism of airway mucous hypersecretion both in chronic bronchitis and bronchial asthma. Dexamethasone substantially decreased airway inflammation and MUC protein expression. It have shown that dexamethasone nonspecific downregulate STAT then decrease the mediators of inflammation which stimulating mucin production. The inhibition of glucocorticoid in different chronic airway inflammation may have potential therapeutic role in chronic bronchitis and bronchial asthma.