Yuan Hao, Luo Bai-ling, He Bai-mei
Department of Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2011 Jul;34(7):523-7.
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.
研究红霉素在慢性阻塞性肺疾病（COPD）进程中的保护机制。
将36只清洁级雄性Wistar大鼠，体重（220±20）g，随机分为3组，每组12只：对照组、COPD模型组和红霉素治疗组。测定大鼠肺功能及病理变化，采用免疫组织化学和逆转录聚合酶链反应（RT-PCR）评估大鼠肺组织中转化生长因子-β(1)（TGF-β(1)）和分泌型白细胞蛋白酶抑制剂（SLPI）的表达。采用方差分析、组间两两比较用SNK-q检验、Pearson直线相关分析进行统计学分析。
COPD模型组大鼠表现为活动减少、食欲不振、体重减轻、毛发干枯发黄，有时伴有喘息，而红霉素治疗组上述表现较少或较轻。与对照组[（83±7）%和（0.33±0.16）L/cm H₂O]相比，模型组的第0.3秒用力呼气容积（FEV(0.3)）/用力肺活量（FVC）[（58±7）%]和动态顺应性（Cdyn）[（0.16±0.07）L/cm H₂O，1 cm H₂O = 0.098 kPa]显著降低，气道阻力（RI）[（0.69±0.14）cm H₂O×L⁻¹×s⁻¹]，但显著高于对照组[（0.33±0.11）cm H₂O×L⁻¹×s⁻¹]。与模型组[（58±7）%和（0.16±0.07）L/cm H₂O]相比，红霉素治疗组的FEV(0.3)/FVC[（65±9）%]和Cdyn[（0.23±0.08）L/cm H₂O]显著升高，RI[（0.50±0.13）cm H₂O×L⁻¹×s⁻¹]，但显著低于模型组[（0.69±0.14）cm H₂O×L⁻¹×s⁻¹]。与模型组（10.7±1.9和0.66±0..18）相比，红霉素治疗组TGF-β(1)蛋白（积分光密度值）和mRNA（吸光度值）（6.7±1.5和0.45±0.13）的表达较低，但SLPI蛋白（积分光密度值）和mRNA（吸光度值）（9.9±1.7和0.69±0.34）的表达高于模型组（8.1±1.7和0.41±0.27）。TGF-β(1)和SLPI的表达呈负相关（r = -0.686，P < 0.05）。
COPD大鼠支气管和肺组织中SLPI表达降低，而TGF-β(1)表达显著增加。红霉素可抑制气道炎症，减少TGF-β(1)对SLPI的抑制作用，提示红霉素具有部分保护作用。
