红霉素预防兔气管损伤后气管狭窄研究

目的 探讨红霉素在预防兔气管损伤后气管狭窄的作用及机制.方法 18只新西兰大耳白兔随机分为阴性对照组、模型对照组、红霉素治疗组,每组均行气管切开,阴性对照组气管切开后直接缝合气管,其余2组气管切开尼龙刷刮除气管黏膜后缝合气管.红霉素治疗组术前7d开始给予红霉素13.6mg/kg,每日灌胃至术后10 d,阴性对照组、模型对照组每日灌胃等量生理盐水.术后10 d处死兔子,收集气管组织,HE染色检查气管组织病理学改变并测量气管狭窄率;实时定量PCR检测各组气管组织转化生长因子β1 (TGF-β1) mRNA表达;免疫组化法检测气管组织Ⅰ型胶原蛋白、Ⅲ型胶原蛋白的表达.结果 红霉素治疗组气管狭窄率为(35.11±4.50)％,阴性对照组气管狭窄率为(11.96±3.26)％,模型对照组气管狭窄率为(53.95±7.09)％,红霉素治疗组气管狭窄率低于模型对照组(t=13.98,P＜0.05).组织病理学结果显示,模型对照组气管狭窄组织中较多炎性细胞浸润,成纤维细胞大量增殖,大量小血管生成,而红霉素治疗组炎性细胞浸润、成纤维化细胞增殖、小血管生成均减少.红霉素治疗组TGF-β1 mRNA相对表达量较模型对照组减少(t=4.55,P＜0.05).免疫组化结果显示,红霉素治疗组的工型胶原蛋白、Ⅲ型胶原蛋白的表达量均较模型对照组明显降低(P值均＜0.05).结论 红霉素可能通过抗炎,下调TGF-β1、Ⅰ型胶原蛋白、Ⅲ型胶原蛋白表达,减轻兔气管损伤后气管狭窄.

Study of prevention effect of erythromycin on tracheal stenosis in tracheal injury rabbit models

Objective To explore the mechanism of prevention effect of erythromycin on tracheal stenosis in tracheal injury rabbit models.Methods Eighteen rabbits were randomly divided into three groups.The trachea were directly closed after tracheotomy in negative control group,the tracheal mucosa was scraped by a nylon brush after tracheotomy in model control group and erythromycin treated group.On the seventh day before operation,the rabbits in erythromycin treated group received intragastric administration of 13.6 mg/kg erythromycin daily until the tenth day after operation,the rabbits in negative control group and model control group received equivalent saline daily.Pathological changes and the degree of stenosis were assessed by hematoxylin and eosin staining,transforming growth factor-β1 (TGF-β1) mRNA expression was determined by real-time polymerase chain reaction,and the expressions of type Ⅰ collagen and type Ⅲ collagen were detected by immunohistochemistry.Results The tracheal stenosis rate was respectively (35.11 ± 4.50)％,(11.96 ± 3.26)％,and (53.95 ± 7.09)％ in erythromycin treated group,negative control group,and model control group.The tracheal stenosis rate in erythromycin treated group was lower than that in model control group (t =13.98,P ＜0.05).Pathology result showed more inflammatory cell infiltration,fibroblast proliferation,and a large number of small angiogenesis in model control group,but these features were reduced in erythromycin treated group.The expression of TGF-β1 mRNA in erythromycin treated group was lower than that in model control group (t =4.55,P ＜0.05).Immunohistochemistry result showed that the expressions of type Ⅰ collagen and type Ⅲ collagen in tracheal stenosis tissue of erythromycin treated group were down-regulated compared with model control group (all P ＜0.05).Conclusions Erythromycin has a preventive effect on tracheal stenosis through the down-regulation of expressions of TGF-β1,type Ⅰ collagen and type Ⅲ collagen in tracheal injury rabbits.