Effect Of Azithromycin On Airway Inflammation And Airway Mucus Hypersecretion In Rats With Chronic Obstructive Pulmonary Disease

Objective: To investigate the preventive and therapeutic effects of azithromycin on the rats with chronic obstructive pulmonary disease from the perspective of airway inflammation and mucus hypersecretion.Methods: Eighteen male SD rats were randomly divided into three groups : control group, COPD model group and azithromycin treatment group. The COPD model was established by intratracheal instillation of lipopolysaccharide and combined with cigarette smoking. HE staining was applied to inspect the pathological changes of the bronchial and lung tissues, and to measure the thickness of tracheal wall and smooth muscle of the rats. AB-PAS was utilized to observe the rats’ airway goblet cells. A pulmonary function instrument was used to measure the FVC, FEV0.1 and PEF. ELISA was used to detect the levels of interleukin 8(IL-8), IL-17 and tumor necrosis factor α(TNF-α) in bronchi alveolar lavage fluid. Immunohistochemistry techniques were used to detect the expression of NF-κB、Muc5ac and TLR4 protein in bronchial and lung tissues. Western Blot was used to detect the expression of MUC5 ac and TLR4 protein, and RT-PCR to detect that of MUC5 ac and TLR4 m RNA in bronchial and lung tissues of the rats.Results: Compared with the control group, the HE and AB-PAS staining of bronchial and lung tissues in the model group rats were consistent with COPD. The thickness of tracheal wall and smooth muscle increased significantly(P<0.05).The levels of FVC(the model group2.13±0.25 ml,the control group7.53±0.88ml),FEV0.1(the model group0.51±0.30 ml, the control group4.46±0.12ml) and PEF(the model group18.46±0.83L/min,the control group31.43±1.46 L/min) decreased greatly(P<0.05). The levels of IL- 8(the model group 605.0±48.7ng/L, the control group 341.2±21.4ng/L),IL- 17(the model group 89.9±6.9 ng/L, the control group 56.0±2.9 ng/L) and TNF-α(the model group212.6±10.7 ng/L, the control group 127.5±9.0 ng/L) in the BALF in the model group increased significantly(P<0.05).The NF-κB,MUC5 ac and TLR4 protein levels of the model group increased higher.The MUC5 ac and TLR4 m RNA levels expressed higher than the control group(P<0.05). Compared with the model group, the damage degree of bronchial and lung tissues in the azithromycin treatment group was significantly alleviated. The levels of FVC(5.98±0.47ml), FEV0.1(1.47±0.24ml) and PEF(23.39±1.74 L/min) decreased visibly(P<0.05).The levels of IL-8(475.7±31.8ng/L), IL-17(79.2±5.1 ng/L) and TNF-α(189.5±9.6ng/L) in the BALF also declined visibly(P <0.05). The expression of NF-κB,MUC5 ac and TLR4 protein levels in bronchial and lung tissues of the azithromycin treatment group decreased greatly(P<0.05). The MUC5 ac m RNA and TLR4 m RNA expression levels in bronchial and lung tissues of the azithromycin treatment group descended greatly(P<0.05).Conclusion: Azithromycin can improve the pulmonary function in COPD model rats and reduce pathological damage. It can decrease the levels of IL- 8,IL- 17 and TNF-α in the BALF of COPD model rats and control the expression of the NF-κB, MUC5 ac and TLR4 protein. It can also reduce the expression of MUC5 ac and TLR4 m RNA.In general, Azithromycin may prevent and cure COPD by means of reducing airway inflammation and airway mucus hypersecretion.