Abstract:

Abstract:Objective To study the differences in efficacy of N- Acety- L- cysteine (NAC) and ipratropium bromide alone or co-administered in rats with chronic obstructive pulmonary disease (COPD),and to clarify the mechanism of co-administration.Methods 30 healthy male Wistar rats were randomly divided into blank control group(n=6),model group(n=6),NAC group(n=6),ipratropium bromide group(n=6) and combination of NAC and ipratropium bromide group(n=6).The rat COPD model was established by intratracheal instillation of lipopolysaccharide ( LPS) for 3 times and exposing to cigarette smoke for 3 months.1 week after modeling,on the eighth day the drug NAC or ipratropium bromide were used for 11 weeks alone or in combination.HE staining was used to detect the morphological changes of lung tissue;ELISA was used to determine the changes of serum interleukin-6(IL-6),nitric oxide (NO),tumor necrosis factor-α(TNF-α) expression;blood-gas analyzer was used to measure the changes of arterial blood oxygen indicators.Results The morphological examination results of lung tissue showed that compared with model group,the lung airway remodeling in drug-treated groups were mitigated,especially in combined treatment group.In expression of inflammatory factors of IL-6,NO,TNF-α,the serum concentration of IL-6,NO,TNF-α of model group was respectively high,compared with blank control group,there is statistical significance（P<0.01）.The serum concentration of IL-6,NO,TNF-α of NAC group and ipratropium bromide group was low,compared with model group,there is statistical significance（P< 0.05）.The results of blood gas analysis showed that the value of PaO2 in model group was decreased,compared with blank control group,there was statistical significance（P<0.01);the value of PaO2 was increased(P<0.01).Compared with model group,the values of PaO2 of the rats in NAC group,ipratropium bromide group and combination group were significantly increased(P<0.05 or P<0.01)，and the values of PaCO2 were decreased significantly（P<0.05 or P<0.01).Compared with blank control group,the serum IL-6,NO and TNF-α levels of the rats in model group were significantly increased(P<0.01);compared with model group,the serum IL-6,NO and TNF-α levels of the rats in NAC group,ipratropium bromide group and combination group were significantly decreased(P<0.05).Conclusion Combination of ipratropium bromide and NAC can prevent lung function of COPD rats from decreasing,and control the progression of early COPD.

Key words: chronic obstructive pulmonary disease, lung function, airway remodeling, ipratropium bromide, N-Acety-L-cysteine