摘要
目的探讨p38丝裂原活化蛋白激酶（p38 MAPK）抑制剂SB203580对慢性阻塞性肺疾病（COPD）大鼠气道黏液高分泌的影响及可能机制。方法将大鼠随机分为空白对照组（NS组）、SB203580对照组（SB组）、COPD模型组（COPD组）以及SB203580干预组（COPD＋SB组）。采用气道内滴入脂多糖联合香烟烟雾熏吸法制备COPD大鼠模型。于造模当天开始每天给药,SB组及COPD＋SB组给予SB203580（3 mg/kg）腹腔注射,NS组及COPD组给予等量生理盐水,于实验第29天处死各组大鼠,行苏木精-伊红（HE）染色,观察大鼠肺组织病理变化,应用免疫组化和免疫电泳法分别测定大鼠肺组织中黏蛋白（MUC5AC）、基质金属蛋白酶-9（MMP-9）及磷酸化的p38 MAPK（p-p38 MAPK）蛋白的含量。结果 COPD组大鼠肺组织符合典型的COPD气道黏液高分泌表现,证明造模成功。与NS组比较,COPD组大鼠肺组织MUC5AC、MMP-9、p-p38 MAPK表达明显增高（F=3.23~6.95,P〈0.01）;与COPD组比较,COPD＋SB组肺组织MUC5AC、MMP-9、p-p38 MAPK表达明显降低（F=3.53~8.36,P〈0.01）。结论 p38 MAPK抑制剂SB203580可减轻COPD大鼠气道黏液分泌,其机制可能通过调控MMP-9的表达,从而下调MUC5AC的表达来实现。
Objective To investigate the effect of p38 mitogen activated protein kinase（p38 MAPK）inhibitor SB203580 on airway mucus hypersecretion and its possible mechanism in a rat model of chronic obstructive pulmonary disease（COPD）.Methods Wistar rats were randomized to normal group（NS group）,SB203580-control group（SB group）,COPD group and SB203580-intervention group（COPD＋SB group）.A rat model of COPD was created with intratracheal instillation of LPS combined with cigarette smoke.Starting from the day of modeling,the rats in SB group and COPD＋SB group were given intraperitoneal injection of SB203580（3mg/kg）,respectively,once a day,and those in the NS and COPD groups were given intraperitoneal equal-volume of normal saline.The rats in each group were sacrificed on day 29.HE stainig was done to observe the pathology of lung tissue.The contents of MUC5 AC and MMP-9in lung tissue were detected using histoimmunochemical method,and that of p38 MAPK and p-p38 MAPK detected with Western blot. Results The pathology of lung tissue in COPD group was consistent with typical manifestations of airway mucus hypersecretion in COPD lung,demonstrating success of modeling.Compared with NS group,the expressios of p-p38 MAPK,MMP-9 and MUC5 AC in lung tissue of COPD group were significantly higher（F=3.23-6.95,P〈0.01）.Compared with COPD group,the expressions of MMP-9,p-p38 MAPK and MUC5 AC in lung tissue of COPD＋SB group were lower（F=3.53-8.36,P〈0.01）. Conclusion p38 MAPK inhabitor SB203580 can reduce airway mucus secretion in COPD rats.Its mechanism may be through regulating the expression of MMP-9 and thus down the expression of MUC5 AC to achieve.
出处
《齐鲁医学杂志》
2016年第5期527-530,共4页
Medical Journal of Qilu
