摘要
目的:研究N-乙酰半胱氨酸(NAC)通过调控表皮生长因子受体/丝裂原活化蛋白激酶(EGFR/MAPK)信号通路对慢性阻塞性肺疾病(COPD)气道黏液高分泌的作用。方法:30只雄性清洁级Wistar大鼠,随机分为3组,各10只,对照组为健康大鼠,模型组为COPD气道黏液高分泌大鼠,NAC组自造模起予以3 mmol/kg 100 μL NAC,共30 d,比较各组肺组织病理结果、气道阻力(RL)和动态顺应性(Cdyn)、血气分析[动脉血二氧化碳分压(PaCO 2)、动脉血氧分压(PaO 2)]、黏膜层厚度/支气管壁厚度(Reid指数)、气道上皮阳性杯状细胞/总上皮细胞数、EGFR/MAPK信号通路蛋白[EGFR、磷酸化应激活化蛋白激酶(p-JNK)/总JNK、磷酸化-丝裂原活化蛋白激酶p38(p-P38MAPK)/总P38、磷酸化细胞外调节蛋白激酶(p-ERK)/总ERK、黏蛋白5AC(MUC5AC)]表达。结果:对照组上皮细胞、气道黏膜上皮、黏膜下腺体、支气管管壁无异常,管腔无分泌物;模型组肺间质血管充血,肺泡间隔变薄、断裂,相邻肺泡融合形成较多囊腔,上皮细胞存在明显增厚、增生、坏死脱落,黏膜下腺体肥大,杯状细胞增生,支气管周围炎性细胞浸润明显,管壁平滑肌束萎缩、断裂;NAC组与对照组相比,存在异常,但与模型组相比,各病理特征均减轻;模型组Cdyn、PaO 2低于对照组,RL、PaCO 2高于对照组(P<0.05);NAC组Cdyn、PaO 2高于模型组,RL、PaCO 2低于模型组(P<0.05);模型组Reid指数、阳性杯状细胞/总上皮细胞数高于对照组(P<0.05);NAC组Reid指数、阳性杯状细胞/总上皮细胞数低于模型组,但与对照组相比,差异仍具有统计学意义(P<0.05);模型组p-JNK/JNK、p-P38/P38、p-ERK/ERK、MUC5AC高于对照组(P<0.05);NAC组p-JNK/JNK、p-P38/P38、p-ERK/ERK、MUC5AC低于模型组,但与对照组相比,差异仍具有统计学意义(P<0.05)。结论:N-乙酰半胱氨酸能通过抑制EGFR/MAPK信号通路表达,改善慢性阻塞性肺疾病支气管黏液腺体增生、杯状细胞广泛化生,抑制气道黏液高分泌状态,提高大鼠肺功能。
AIM: To investigate the role of N-acetylcysteine (NAC) in the regulation of epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) signaling pathway in airway mucus hypersecretion in chronic obstructive pulmonary disease (COPD) effect. METHODS: Thirty male clean Wistar rats were randomly divided into 3 groups, 10 in each group. The control group was healthy rats. The model group was COPD airway mucus hypersecretion rats. The NAC group was given 3 mmol/ from the modeling. NAC group received 3 mmol/kg 100 μL NAC for 30 days. The pathological results of lung tissue, airway resistance (RL) and dynamic compliance (Cdyn), blood gas results[arterial blood carbon dioxide partial pressure (PaCO 2), arterial oxygen partial pressure (PaO 2)], mucosal thickness / bronchial wall thickness (Reid index), airway epithelial positive goblet cells / total epithelial cell number, EGFR/MAPK signaling pathway protein[EGFR, phosphorylation stress activated protein kinase (p-JNK)/Total JNK, phosphorylation-mitogen-activated protein kinase p38 (p-P38MAPK)/total P38, phosphorylated extracellular regulated protein kinase (p-ERK)/total ERK, mucin 5AC (MUC5AC)] expression were observed and compared. RESULTS:There were no abnormalities in the epithelial cells, airway mucosa epithelium, submucosal glands, and bronchial wall of the control group. There was no secretion in the lumen. The model group showed pulmonary interstitial vascular congestion, thinning and rupture of the alveolar space, and the formation of adjacent alveolar fusion. Polycystic cavity, epithelial cells have obvious thickening, hyperplasia, necrosis, submucosal gland hypertrophy, goblet cell hyperplasia, inflammatory cell infiltration around the bronchi, atrophy and rupture of smooth muscle bundle;compared with control group tube in NAC showed no abnormalities, but compared with the model group, the pathological features were alleviated;Cdyn and PaO 2 in the model group were lower than those in the control group, RL and PaCO 2 were higher than those in the control group (P<0.05);Cdyn and PaO 2 in the NAC group were higher than those in the model group. RL and PaCO 2 were lower than those in the model group (P<0.05);the Reid index, positive goblet cells/total epithelial cells in the model group were higher than those in the control group (P<0.05);Reid index, positive goblet cells/total epithelial cells in the NAC group were lower than those in the model group, but the difference was statistically significant compared with those in the control group (P<0.05). p-JNK/JNK, p-P38/P38, p-ERK/ERK, MUC5AC of the model group were higher than those in the control group.(P<0.05);p-JNK/JNK, p-P38/P38 p-ERK / ERK, MUC5AC of NAC group were lower than those in the model group as compared with the control group(P<0.05). CONCLUSION: N-acetylcysteine can inhibit the expression of EGFR/MAPK signaling pathway, improve bronchial mucosal gland hyperplasia, goblet cell hyperplasia, inhibit airway mucus hypersecretion and improve rat lung features.
作者
白学敏
邹立考
金珍木
姜利佳
BAI Xuemin;ZOU Likao;JIN Zhenmu;JIANG Lijia(Department of Pharmacy, Wenzhou Central Hospital, Wenzhou 325000, Zhejiang, China;Outpatient Department of Wenzhou Departing Cadre Restoration, Zhejiang Military Region, Wenzhou 325000, Zhejiang, China;Department of Rheumatology, Wenzhou Central Hospital, Wenzhou 325000, Zhejiang, China;Department of Gastroenterology, Wenzhou Central Hospital, Wenzhou 325000, Zhejiang, China)
出处
《中国临床药理学与治疗学》
CAS
CSCD
2019年第10期1120-1127,共8页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
浙江省医药卫生科技计划项目(2013KYB251)
