联合应用红霉素、青霉素及布地奈德预防兔气管狭窄的初步研究

发布时间：2018-06-04 09:03

本文选题：红霉素 + 青霉素　；参考：《广西医科大学》2017年硕士论文

【摘要】：目的:建立兔气管损伤后气管狭窄的模型,并通过比较各组气管狭窄率、病理改变,检测TGF-β1 mRNA、Col-I、Col-III的表达,初步探讨联合应用红霉素、青霉素及布地奈德预防兔气管损伤后气管狭窄的效果及可能的机制。方法:36只家兔(雌雄不限),体重2.5kg-3.0kg。随机分为阴性对照组、模型对照组、青霉素组、布地奈德组、红霉素组、红霉素联合青霉素+布地奈德组(联合用药组),每组6只,每组均在全身麻醉下行气管切开,阴性对照组气管切开后直接缝合气管(不给予气管刷擦),其余各组均行气管切开后,予硬质尼龙均匀用力来回刷擦20次气管内膜各壁刷刮除气管黏膜后间断缝合气管。红霉素采用灌胃法给药,13.6mg/kg,每日2次;青霉素采用肌注给药,4.35万单位/kg,每日2次;布地奈德采用雾化吸入给药,0.05mg/kg,每日2次。均于术前7天开始给药至术后10天。术后10天处死兔子,收集气管组织,HE染色后光学显微镜下,观察测量气管狭窄率及气管组织病理学改变;qRT-PCR法检测各组气管组织TGF-β1 mRNA的相对表达量;免疫组织化学法检测各组气管组织中Col-I、Col-III的表达情况。结果:⑴管腔狭窄率比较:联合用药组管腔狭窄率为(28.17±3.38)%,显著低于模型对照组(53.95±7.09)%、青霉素组(44.78±4.03)%、布地奈德组(49.90±5.47)%、红霉素组(35.11±4.50)%,(t值分别为9.29、5.98、7.83和2.50,均P0.05)。⑵组织病理学比较:阴性对照组的黏膜、黏膜下层和外层清晰可见,黏膜下层纤维结缔组织疏松,见少量淋巴细胞、成纤维细胞,未见小血管增生;模型对照组可见大量炎症细胞浸润、成纤维细胞增殖及大量新生小血管;联合用药组见少量炎症细胞浸润,未见明显成纤维细胞、小血管增生。⑶气管组织中TGF-β1 mRNA的相对表达量:联合用药组TGF-β1 mRNA相对表达量显著低于模型对照组、青霉素组、布地奈德组、红霉素组,差异均有统计学意义(均P0.05);布地奈德组TGF-β1 mRNA的相对表达量与模型对照组比较,差异无统计学意义(P0.05)。⑷气管组织中Col-I、Col-III的表达:Col-I、Col-III主要表达于黏膜下层细胞外基质中;联合用药组Col-I、Col-III平均光密度值显著低于模型对照组、青霉素组、布地奈德组、红霉素组,差异均有统计学意义(均P0.05);布地奈德组Col-I、Col-III平均光密度值与模型对照组比较,差异无统计学意义(P0.05)。结论:⑴.单独应用红霉素、青霉素、布地奈德雾化吸入并不能明显减轻兔气管损伤后的气管狭窄。(2).联合应用红霉素、青霉素、布地奈德可能通过抗炎、抗感染,下调TGF-β1 mRNA、Col-I、Col-III的表达,有效减轻兔气管损伤后的气管狭窄,可考虑应用于防治气管损伤后气管狭窄。
[Abstract]:Objective: to establish a rabbit model of trachea stenosis after trachea injury, and to detect the expression of TGF- 尾 1 mRNA-Col-I Col-III by comparing the rate and pathological changes of trachea stenosis in each group, and to explore the application of erythromycin combined with TGF- 尾 1 mRNA-Col-III. Effect of penicillin and budesonide on prevention of trachea stenosis after tracheal injury in rabbits and its possible mechanism. Methods Thirty six rabbits (male and female, weight 2.5kg-3.0 kg) were used. They were randomly divided into negative control group, model control group, penicillin group, budesonide group and erythromycin combined with penicillin budesonide group. In the negative control group, the trachea was sutured directly after tracheotomy (no trachea brushes were given, and the other groups were treated by tracheotomy, then the endotracheal membrane was scraped and scraped for 20 times with the hard nylon evenly applied back and forth, and the trachea was sutured intermittently after scraping the trachea mucosa. Erythromycin was given 13.6 mg / kg twice a day, penicillin 43500 unit / kg twice daily and budesonide 0.05 mg / kg twice a day. The drug was administered 7 days before operation and 10 days after operation. The rabbits were killed 10 days after operation. The tracheal stenosis rate and the histopathological changes of trachea were observed under optical microscope after HE staining. The relative expression of TGF- 尾 1 mRNA in trachea was detected by qRT-PCR. The expression of Col-Ig Col-III in trachea was detected by immunohistochemical method. Results comparison of the stenosis rate of 1: 1 lumen: the stenosis rate of the combined drug group was 28.17 卤3.38, which was significantly lower than that of the model control group (53.95 卤7.09), penicillin group (44.78 卤4.03g), budesonide group (49.90 卤5.47) and erythromycin group (35.11 卤4.50), respectively. The histopathological comparison was P0.05.2 for the negative control group. The submucosa and outer layer were clearly visible, the submucosal fibrous connective tissue was loose, a small amount of lymphocytes, fibroblasts, and no small vessel hyperplasia were seen, while in the model control group, a large number of inflammatory cells were infiltrated. The proliferation of fibroblasts and a large number of small vessels were observed in the combination group, and a small amount of inflammatory cells were infiltrated in the combined treatment group, but no obvious fibroblasts were found in the combination group. The relative expression of TGF- 尾 1 mRNA in tracheal tissue of small vascular hyperplasia was significantly lower in combination group than that in model control group, penicillin group, budesonide group, erythromycin group, penicillin group, budesonide group and erythromycin group. The relative expression of TGF- 尾 1 mRNA in budesonide group was not significantly different from that in model control group. The average optical density of Col-Ion Col-III in combination group was significantly lower than that in model control group, penicillin group, budesonide group and erythromycin group (all P 0.05), and the average optical density of Col-Ignide Col-III in budesonide group was significantly lower than that in model control group. The difference was not statistically significant (P 0.05). Conclusion 1. Aerosol inhalation of erythromycin penicillin and budesonide alone could not significantly reduce tracheal stenosis after trachea injury in rabbits. In combination with erythromycin, penicillin and budesonide, the expression of TGF- 尾 1 mRNA-Col-III may be down-regulated by anti-inflammation and anti-infection, which can effectively reduce tracheal stenosis after trachea injury in rabbits. It can be used to prevent and treat tracheal stenosis after trachea injury.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R56

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