红霉素对哮喘豚鼠嗜酸性粒细胞凋亡的影响

Effect of erythromycin on eosinophil apoptosis in allergic asthmatic guinea pig

目的探讨红霉素对哮喘豚鼠嗜酸性粒细胞凋亡的影响。方法用卵白蛋白致敏复制哮喘豚鼠模型,分为哮喘组、地塞米松治疗组,及小、中、大剂量红霉素组6组。检测各组豚鼠支气管肺泡灌洗液(BALF)中白细胞总数、嗜酸性粒细胞(EOS)总数、EOS百分数,分离纯化BALF的EOS,用吖啶橙/溴乙啶(AO/EB)荧光染色法检测EOS凋亡率。结果①豚鼠BALF白细胞总数、EOS总数及EOS百分数哮喘组均明显高于正常对照组,各红霉素组与哮喘组相比均有所降低,但小剂量红霉素组与之相比差异无显著性;②豚鼠BALF中EOS凋亡率哮喘组明显低于正常对照组,各红霉素组均高于哮喘组,但小剂量红霉素组与之相比差异无显著性;③EOS凋亡率与BALFEOS总数及EOS百分数呈显著负相关。结论红霉素具有一定的抗气道非特异性炎症作用,可以诱导EOS凋亡,这可能是其抗哮喘炎症作用的主要机制之一。

Objective To investigate the effect of erythromycin on eosinophil apoptosis in allergic asthmatic guinea pig. Methods The asthmatic guinea pig model was established by ovalbumin treatment （OVA）. Guinea pigs were randomly divided into six groups：①normal control group, ②asthma group, ③dexamethasone treated group, ④low dose erythromycin treated group, Omoderate dose erythromycin treated group, ⑤high dose erythromyon treated group. The total cell count, the number of EOS and the percentage of EOS in bronchoalveolar lavage fluid （BALF） of guinea pigs were examined. The EOS was purified from BALF and then its apoptosis were detected by acridine orange/ethidium bromide （AO/EB） double fluorescence-staining assay. Results （1） The total cell counts, the number of EOS and the percentage of EOS in BALF of asthma group were higher than that of normal group. However, after the administration of different doses of erythromycin, the total cell counts, the number of EOS and the percentage of EOS in BALF of asthma group decreased, which were lower than that of asthma group, but no significant difference being noted between the low dose erythromycin group and the asthma group. （2） The number of apoptotic EOS in asthma group reduced. All erythromycin groups with different doses accelerated EOS apoptosis, but the changes in low dose erythromycin group didn＇ t differ from that in asthma group. （3） There were negative correlations between the logarithm of the EOS apoptosis percentage and the number of EOS, and the percent of EOS in BALF. Conclusions Erythromycin has an anti-inflammatory effect. Erythromycin-induced eosinophil apoptosis may be an important mechanism of asthma.