The effect of erythromycin on transforming growth factor-β(1) and secretory leukocyte proteinase inhibitor in a rat model of chronic obstructive pulmonary disease

Abstract

To study the protective mechanism of erythromycin in the process of COPD. Thirty-six male Wistar rats, grade SPF, weight (220 ± 20) g, were randomly divided into 3 groups, 12 each: a control group, a COPD model group and an erythromycin treated group. Measurement of rat pulmonary function and the pathological changes were performed, and the expression of transforming growth factor-β(1) (TGF-β(1)) and secretory leukocyte proteinase inhibitor (SLPI) in the lung of rats were evaluated by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Analysis of variance, pairwise comparison between groups using SNK-q test, Pearson linear correlation analysis were carried out for statistical analysis. The rats in the COPD model group showed sign of less activity, loss of appetite and weight, dry and yellow hair, and sometimes wheezing, which were less or milder in the group treated with erythromycin. FEV(0.3)/FVC [(58 ± 7)%] and Cdyn [(0.16 ± 0.07) L/cm H2O, 1 cm H2O = 0.098 kPa] were significantly lower in the model group as compared to the control group [(83 ± 7)% and (0.33 ± 0.16) L/cm H2O], RI [(0.69 ± 0.14) cm H2O×L(-1)×s(-1)], but was significantly higher than the control group [(0.33 ± 0.11) cm H2O×L(-1)×s(-1)]. FEV(0.3)/FVC [(65 ± 9)%] and Cdyn [(0.23 ± 0.08) L/cm H2O] were significantly higher in the erythromycin treated group as compared to the model group [(58 ± 7)% and (0.16 ± 0.07) L/cm H2O], RI [(0.50 ± 0.13) cm H2O×L(-1)×s(-1)], but was significantly lower than the model group [(0.69 ± 0.14) cm H2O×L(-1)×s(-1)]. The expression of TGF-β(1)protein (integral optical density value) and mRNA (absorbance value) (6.7 ± 1.5 and 0.45 ± 0.13) were lower in the erythromycin treated group as compared to the model group (10.7 ± 1.9 and 0.66 ± 0.18), but the expression of SLPI protein (integral optical density value) and mRNA (absorbance value) (9.9 ± 1.7 and 0.69 ± 0.34) were higher than those of the model group (8.1 ± 1.7 and 0.41 ± 0.27). The expressions of TGF-β(1)and SLPI were negatively associated (r = -0.686, P < 0.05). The expression of SLPI was decreased but the expression of TGF-β(1)was increased significantly in the bronchial and lung tissues of rats with COPD. Airway inflammation was inhibited by erythromycin which was able to reduce the inhibitory effect of TGF-β(1)to SLPI, indicating a partial protective effect of erythromycin.