罗格列酮抑制慢性阻塞性肺疾病模型大鼠炎性反应的机制研究  

The protective effects of rosiglitazone in chronic obstructive pulmonary disease rat models

作　　者：钟莲娣 张春来[1] 左万里[1] 周伟[2] 黄胜起[3] 张鑫[2,4] 黄炎明[1,4] ZHONG Liandi;ZHANG Chunlai;ZUO Wanli;ZHOU Wei;HUANG Shengqi;ZHANG Xin;HUANG Yanming(Department of Respiration Medicine, Jiangmen Central Hospital, Jiangmen, Guangdong 529030, P. R. China;Department of Pathology, ]iangmen Central Hospital, ]iangmen, Guangdong 529030, P. R. China;Department of Clinical Laboratory, Jiangmen Central Hospital, Jiangmen, Guangdong 529030, P. R. China;Clinical Experimental Center, ]iangmen Central Hospital, ]iangrnen, Guangdong 529030, P. R. China)

机构地区：[1]江门市中心医院呼吸内科,广东江门529030 [2]江门市中心医院病理科,广东江门529030 [3]江门市中心医院检验科,广东江门529030 [4]江门市中心医院中心实验室,广东江门529030

出　　处：《中国呼吸与危重监护杂志》2018年第3期230-236,共7页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：广东省公益研究与能力建设专项资金(2014A020212377);广东省医学科研基金(A2017103);广东省中医药局科研项目(20181273)

摘　　要：目的利用气管内滴注脂多糖联合香烟烟雾暴露建立慢性阻塞性肺疾病(简称慢阻肺)大鼠模型,观察罗格列酮对模型大鼠炎性反应的保护作用。方法 50只SPF级成年雄性Wistar大鼠随机均分为5组,每组各10只。利用气管内滴注脂多糖联合香烟烟熏法,在4组大鼠中构建慢阻肺模型,3个实验组分别加以0.1 mg/kg、0.15 mg/kg和0.2 mg/kg罗格列酮灌胃,共30 d;模型组、健康对照组则给予生理盐水。实验结束后,使用颈部脱臼法处死大鼠,取右肺进行苏木精-伊红染色,进行气道炎症病理评分并计算平均内衬间隔(MLI)和平均肺泡数(MAN),检测肺组织中p-Stat3和p-NF-κB表达水平。结果相对于健康对照组,模型组大鼠可见明显的气管炎性反应和肺气肿病理改变,给予梯度浓度的罗格列酮,其上述病理改变较模型组减轻,其中0.2 mg/kg罗格列酮组大鼠的气道炎症病理评分最低,但三组间MLI和MAN差异无统计学意义。相对于健康对照组,模型组大鼠气管中受浸润的淋巴组织、气管黏膜上皮及肺组织中p-Stat3和p-NF-κB表达均显著升高,给予梯度浓度的罗格列酮后,淋巴组织、气管黏膜上皮及肺组织中p-NF-κB表达下降,淋巴组织中p-Stat3下降,气管黏膜上皮及肺组织中p-Stat3表达不受影响。结论罗格列酮能通过抑制NF-κB信号通路,抑制慢阻肺肺组织中的炎性反应,从而减轻肺实质的损伤和气道炎症程度,延缓慢阻肺的进程。Objective To investigate the protecting effect of rosiglitazone for lung in airway-instillationlipopolysaccharides and smoke-induced chronic obstructive pulmonary disease（COPD） rat models. Methods Fifty male Wistar rats with the SPF standard were randomly divided into 5 groups（n=10）. The rats were treated by airwayinstillation-lipopolysaccharides and exposing to smoking to establish COPD rat models excepted normal group, and the treatment groups were received gavage rosiglitazone of 0.1 mg/kg, 0.15 mg/kg, and 0.2 mg/kg rosiglitazone daily for 30 days, and the normal group or model group was received gavage normal saline. All rats were sacrificed after 30 days＇ treatment, and the lung tissue section was stained by hematoxylin and eosin. The mean linear intercept（MLI） and mean alveolar numbers（MAN） were measured in all groups. In addition, the protein levels of p-Stat3 and p-NF-κB were detected by immunohistochemistry. Results Compared with normal group, the inflammation and emphysema were observed in the lung of rats in model group, and the symptoms of the group treated with rosiglitazone were lighter than normal group. The lungs of rats treated with highest dose of rosiglitazone（0.2 mg/kg） were evaluated with lowest pathology assessment score among three treatment groups, but there was no significant difference of MLI or MAN among three treatment groups. Compared with normal group, the protein levels of p-Stat3 and p-NF-κB were increased in the lung and tracheal epithelium and lymphoid tissue of rats in model group, while the protein levels of p-NF-κB were decreased in these tissues and the protein levels of p-Stat3 were decreased in the lymphoid tissue after treatment with rosiglitazone, but the protein levels of p-Stat3 were not changed in the lung and tracheal epithelium. Conclusion Rosiglitazone has a protective effect on the COPD rat models by inhibiting NF-κB pathway to reduce the inflammation of the lung parenchyma.

关 键 词：慢性阻塞性肺疾病 罗格列酮 气道炎症 

分 类 号：R-332[医药卫生] R563.9