噻托溴铵对慢性阻塞性肺疾病大鼠膈肌纤维的影响

Effects of Tiotropium Bromide on Diaphragm Fibers in A Rat Model of Chronic Obstructive Pulmonary Disease

目的探讨噻托溴铵对慢性阻塞性肺疾病(简称慢阻肺)大鼠膈肌功能的调节作用及其机制。方法 60只雄性Wistar大鼠随机分成对照组、慢阻肺组和噻托溴铵组。在慢阻肺组和噻托溴铵组采用烟熏及气管内注射脂多糖建立大鼠慢阻肺模型,噻托溴铵组大鼠在每次烟熏前30 min雾化吸入噻托溴铵(0.12 mmol/L,10 min)。第91 d将大鼠处死,观察各组大鼠肺组织的病理变化、膈肌纤维类型改变和膈肌细胞凋亡率的变化。结果肺组织病理学显示慢阻肺大鼠模型成功。噻托溴铵组大鼠肺气肿程度较慢阻肺组略轻。对照组大鼠膈肌Ⅱ型纤维比例为(64.64±1.86)%,Ⅰ型纤维比例为(36.24±2.25)%;慢阻肺组大鼠膈肌Ⅱ型纤维的比例显著降低,为(55.35±2.46)%,Ⅰ型纤维比例显著增加,为(48.82±2.34)%;噻托溴铵组介于对照组和慢阻肺组两组之间,Ⅱ型纤维比例为(59.38±2.56)%,Ⅰ型纤维比例为(40.83±1.22)%)。各组膈肌纤维比例差异有统计学意义(P<0.05)。3组大鼠膈肌细胞凋亡率分别为(1.73±0.87)%、(39.73±3.53)%和(25.48±3.35)%,组间差异有统计学意义(P<0.05)。结论噻托溴铵可抑制膈肌细胞过度凋亡,阻止慢阻肺大鼠膈肌纤维由Ⅱ型向Ⅰ型的转变,改善膈肌功能,缓解膈肌疲劳,延缓慢阻肺的进程。

Objective To explore the effects and mechanism of totropium bromide on diaphragm fibers remodeling in rats with chronic obstructive pulmonary disease （COPD）. Methods 60 male Wistar rats were randomly divided into a control group, a COPD group and a tiotropium bromide group. The rat model of COPD was established by passive smoking and intratracheal instillation of lipopolysaccharide in the COPI） group and the tiotropium bromide group. The rats in the tiotropium bromide group were inhaled with tiotropium bromide （0.12 mmol/L, 10 min） 30 min before each smoking. Pathological changes of the lung tissue and airway were observed by HE staining. The diaphragm fibers classification was observed by dyeing. The diaphragmatic muscle cell apoptosis was observed by TUNEL. Results Histopathology proved that COPD rats model was successfully established. The emphysema in the tiotropium bromide group was milder than that in the COPD group. The type lI fibers and type I fibers of diaphragm accounted for （64. 64 ± 1.86） % and （36. 24 ± 2. 25 ） % in the control group, （55. 35 ± 2. d6） % and （48.82± 2. 34） % in the COPD group, （59. 38 ± 2. 56） % and （40. 83 ±1.22 ） % in the tiotropium bromide group, respectively. There were significant differences between three groups in category of diaphragm fibers （ P 〈 0. 05 ）. The apoptosis rate of diaphragmatic muscle cells in three groups was （ 1.73 ± 0. 87） %, （ 39.73 ±3.53 ） % and （25.48 ±3.35 ） %, respectively, with significant difference between three groups （ P 〈 0.05 ）. Conclusion Tiotropium bromide can inhibit over apoptosis of diaphragmatic muscle ceils and prevent diaphragm transfome from type ~ to type I in COPD rats, can alleviate diaphragmatic muscle fatigue and the progression of COPD.