Effect Of TLR4 On Inflammation And Mucus Hypersecretion In Airway Of Rats With Chronic Bronchitis

Part 1 Change of inflammation and mucus secretion in airway of rats with chronic bronchitisObjective To investigate the airway inflammation and the mucus hypersecretion in chronic bronchitic rat. Methods Eightteen Wistar rats were randomly divided into two groups: control group (NS group, n=6), chronic bronchitis model group(LPS group , n=12). The rat model of chronic bronchitis was established by intratracheal instillation 200μg/200μl of lipopolysaccharide (LPS) and daily exposure to LPS smog. After three weeks,total cells and differential inflammatory cells were counted in bronchoalveolar lavage fluid (BALF), the levels TNF-αin BALF were determined by ELISA, the goblet cell of airway wall was observed by AB-PAS staining, the expression of Mucin 5ac (Muc5ac) in airway were observed by immunohistochemical staining,the expressions of Muc5ac mRNA in lung tissue were observed by real time fluorescence quantitative reverse transcription polymerase (RT-PCR). Results Total cells, neutrophil, macrophagus and lymphocyte cells in BALF, the levels of TNF-αin BALF, the goblet cell of airway wall, and the expression of Muc5ac in lung tissue of LPS group were obviously higher than those in control group(P<0.01 or P<0.05). Conclusions These results suggest that chronic bronchitic rat appearance airway chronic inflammation which induced by neutrophil, macrophagus and lymphocyte cells, and have airway mucus hypersecretion. Moreover, airway chronic inflammation and airway mucus hypersecretion have close relationship. Pary 2 Effect of TLR4 on inflammation and mucus hypersecretion in airway of chronic bronchitic rats treated with polymyxin BObjective To investigate the effect of TLR4 on inflammation and mucus hypersecretion in airway of chronic bronchitic rats treated with polymyxin B (PMB). Methods Forty-two rats were randomly divided into five groups: control group (NS group, n=6), chronic bron -chitis model group(LPS group, n=12), polymyxin B(PMB) treatment group(LPS+PMB group, n=10), PMB control group (PMB group,n=8) and dexamethasone (DEX) treatment group(LPS+DEX group, n=6). Total cells and differential inflammatory cells were count -ed in bronchoalveolar lavage fluid (BALF), the levels of TNF-αin BALF were determin -ed by ELISA, the pathomorphological Changes in the lung were analyzed ,the goblet cell of airway wall was observed by alcian blue/periodic acid schiff (AB-PAS) staining, the expressions of Mucin 5ac(Muc5ac) and TLR2 and TLR4 in lung tissue were observed by immuneohistochemical staining, the expressions of Muc5ac mRNA and TLR4 mRNA in lung tissue were observed by RT-PCR. Results The total cells,neutrophil,macrophagus and lymphocyte cells in BALF, the levels of TNF-αin BALF , the goblet cell of airway wall, the expression of Mucus secretion and Muc5ac mRNA in airway, the expression of TLR4 mRNA and TLR4 positive staining and TLR2 positive staining of lung tissu obviously decreased in PMB treatment group and DEX treatment group which compared with chronic bronchitis model group (P<0.05). Conclusions The current studys uggests that TLR4 may induced chronic inflammation and Muc5ac hypersecretion in airway of rats with chronic bronchitis, polymyxin B may inhibit inflammation and mucus hypersecretion in airway of rats with chronic bronchitis, which were mediated by TLR4.