摘要
目的观察清金化痰汤对慢性阻塞性肺疾病(COPD)模型大鼠表皮生长因子受体(EGFR)/MAPK信号通路的影响,探讨其干预COPD气道黏液高分泌的作用机制。方法气管内滴注LPS联合烟熏方法建立COPD气道黏液高分泌模型。实验大鼠随机分为空白组、模型组、清金化痰汤组、克拉霉素组,每组10只。空白组正常饲养,其余3组分别给予生理盐水、清金化痰汤、克拉霉素片灌胃,每日1次,连续30 d。各组大鼠于实验第31日分别处死,HE染色观察肺组织病理形态及黏液腺体增生情况,实时荧光定量PCR检测肺组织EGFR、MUC5AC基因表达,免疫组化检测肺组织及气道上皮P-EGFR、P-ERK、P-JNK、P-p38、MUC5AC蛋白表达。结果与空白组比较,模型组大鼠气道上皮黏液腺体增生及P-EGFR、P-ERK、P-JNK、P-p38、MUC5AC蛋白表达显著升高(P<0.01),MUC5AC m RNA表达升高(P<0.05);与模型组比较,清金化痰汤组大鼠气道上皮黏液腺体增生及P-p38、P-ERK、MUC5AC蛋白表达显著降低(P<0.05,P<0.01),P-JNK蛋白表达显著升高(P<0.01);清金化痰汤组肺组织EGFR、MUC5AC m RNA表达显著降低(P<0.01)。结论清金化痰汤可能通过抑制EGFR下游ERK、p38信号通路,干预COPD气道黏液高分泌。
Objective To observe the effects of Qingjin Huatan Decoction on EGFR/MAPK signaling pathway of airway mucus hypersecretion rats with chronic obstructive pulmonary disease（COPD）. Methods Intratracheal instillation of LPS combined with smudging method was used to establish COPD airway mucus hypersecretion rat models. Experimental rats were randomly divided into blank group, model group, Qingjin Huatan Decoction group and clarithromycin group. The blank group was normally fed, while the other three groups were given NS, Qingjin Huatan Decoction, and clarithromycin respectively for gavage, once a day for 30 days. All rats were killed on the 31 st day, and pathological changes of lung tissue and mucous glands hyperplasia were observed by HE staining method. The gene expressions of EGFR and MUC5 AC in lung tissue were detected by RT-PCR method. The protein expressions of P-EGFR, P-ERK, P-JNK, P-p38 and MUC5 AC in pulmonary tissue and airway epithelium were detected by immunohistochemical method. Results Compared with the blank group, mucous glands hyperplasia on airway epithelium, protein expressions of P-EGFR, P-ERK, P-JNK, P-p38 and MUC5 AC on airway epithelium significantly increased in the model group（P〈0.01）; gene expression of MUC5 AC of lung tissue increased（P〈0.05）. Compared with the model group, mucous glands hyperplasia on airway epithelium, P-p38, P-ERK and MUC5 AC protein expression on airway epithelium in Qingjin Huatan Decoction group significantly decreased（P〈0.05, P〈0.01）; the protein expression of P-JNK increased significantly（P〈0.01）. EGFR and MUC5 AC m RNA in lung tissue in Qingjin Huatan Decoction group decreased significantly（P〈0.01）. Conclusion Qingjin Huatan Decoction can reduce airway mucus hepersecrection of COPD by inhibiting ERK and p38 signal pathway on EGFR downstream.
出处
《中国中医药信息杂志》
CAS
CSCD
2016年第10期56-62,共7页
Chinese Journal of Information on Traditional Chinese Medicine
基金
国家自然科学基金(81473655)
北京市自然科学基金(7132115)
