小剂量红霉素对气管损伤后肉芽组织增生的影响

Effect of low dose erythromycin on the proliferation of granulation tissue after tracheal injury

目的探讨小剂量红霉素对气管损伤后肉芽组织增生的影响。方法将42只家兔按随机数字表法分成A～G共7组各6只；其中A为空白对照组，B为青霉素组，C为红霉素组，D为红霉素＋青霉素组，E为布地奈德组，F为红霉素＋布地奈德组，G为红霉素＋布地奈德＋青霉素组。42只家兔行气管切开后均予尼龙毛刷来回刷20次进行造模。术前1周至术后第9天各组分别予上述药物处理。术后第10天采集血液标本检测转化生长因子β1（TGF－β1）、血管内皮生长因子（VEGF）、白细胞介素（IL）－6、IL－8浓度；并进行气管狭窄度测量。结果A～G组血清中TGF－β1浓度分别为（17.6±1.3）、（18.2±3.1）、（13.0±1.1）、（14.0±1.0）、（21.0±6.1）、（13.6±3.5）、（8.2±1.3）ng/L，VEGF浓度分别为（88.1±4.1）、（85.8±4.3）、（58.1±6.3）、（56.5±2.4）、（87.8±2.8）、（57.0±3.7）、（34.3±6.7）ng/L, IL－6浓度分别为（67.8±4.0）、（66.1±3.5）、（54.1±4.8）、（52.1±3.2）、（64.6±4.9）、（49.4±4.2）、（35.9±3.7）ng/L，IL－8浓度分别为（112.8±5.2）、（116.6±4.1）、（88.0±6.2）、（85.5±3.5）、（114.4±4.6）、（82.6±3.8）、（55.9±6.0）ng/L；C、D、F、G组血清中TGF－β1、VEGF、IL－6、IL－8浓度均显著低于A、B、E组（均P〈0.05），G组浓度均显著低于其他各组（均P〈0.05）。42只家兔气管内均有不同程度的肉芽组织增生致气管狭窄。A～G组气管狭窄度分别为（53.3±4.4）%、（48.2±5.0）%、（24.3±4.4）%、（29.5±3.2）%、（47.8±6.5）%、（27.9±3.1）%、（15.6±2.0）%，C、D、F、G组狭窄度均显著轻于A、B、E组（均P〈0.05），G组狭窄度均显著轻于其他各组（均P〈0.05）。结论小剂量红霉素能有效抑制气管损伤后肉芽组织的增生，与其他抗菌素及糖皮质激素联合用药效果更佳。

ObjectiveTo investigate the effect of low dose erythromycin on the proliferation of granulation tissue after tracheal injury.MethodsForty-two rabbits were randomly divided into 7 groups （n=6 each）, group A （saline control group）, group B （penicillin group）, group C （low dose erythromycin group）, group D （low dose erythromycin and penicillin group）, group E （budesonide group）, group F （low dose erythromycin and budesonide group）, group G （low dose erythromycin, penicillin and budesonide group）. All rabbits received tracheotomy, and the tracheal mucosa was scraped with a nylon brush 20 times for tracheal stenosis model. Rabbits were treated with corresponding drugs from a week before operation to 9 days after operation. The serum concentrations of transforming growth factor - beta 1 （TGF-β1）, vascular endothelial growth factor （VEGF）, interleukin （IL） -6, IL-8 were determined and the tracheal specimens were harvested for measuring degree of stenosis on the 10th day after operation.ResultsSerum concentrations of TGF-β1 in group A, B, C, D, E, F and G were （17.6±1.3）, （18.2±3.1）, （13.0±1.1）, （14.0±1.0）, （21.0±6.1）, （13.6± 3.5）, （8.2±1.3） ng/L; VEGF were （88.1±4.1）, （85.8±4.3）, （58.1±6.3）, （56.5±2.4）, （87.8±2.8）, （57.0±3.7）, （34.3±6.7） ng/L; IL-6 were （67.8±4.0）, （66.1±3.5）, （54.1±4.8）, （52.1±3.2）, （64.6±4.9）, （49.4±4.2）, （35.9±3.7） ng/L; IL-8 were （112.8±5.2）, （116.6±4.1）, （88.0±6.2）, （85.5±3.5）, （114.4±4.6）, （82.6±3.8）, （55.9±6.0） ng/L, respectively. The serum concentrations of TGF-β1, VEGF, IL-6 and IL-8 in group C, D, F and G were significantly lower than those in group A, B and E （all P〈0.05）. Compared with the other groups, the serum concentrations in group G were the lowest （all P〈0.05）. All 42 rabbits had tracheal stenosis with different degrees of proliferation of granulation tissue. The degree of tracheal stenosis in Group A, B, C, D, E, F and G were （53.3±4.4）%, （48.2±5.0）%, （24.3±4.4）%, （29.5±3.2）%, （47.8±6.5）%, （27.9±3.1）%, （15.6±2.0）%, respectively. The degree of tracheal stenosis in group C, D, F and G was significantly lower than that in group A, B and E, which had statistical differences （all P〈0.05）. Compared with the other groups, the degree of tracheal stenosis in group G was the lowest （all P〈0.05）.ConclusionsLow dose of erythromycin can effectively inhibit the proliferation of granulation tissue after tracheal injury in rabbits. And it has better effectiveness when combined with other antibiotics and hormone.