罗格列酮抑制慢性阻塞性肺疾病模型大鼠气道重塑的研究  

Protection of rosiglitazone against airway remodeling in chronic obstructive pulmonary disease rat models

作　　者：黄炎明[1] 钟莲娣 张春来[1] 左万里 周伟[2] 黄胜起[3] 张鑫[4] Huang Yanming ,Zhong Liandi, Zhang Chunlai, Zuo Wanli, Zhou Wei, Huang Shengqi, Zhang Xin.(Department of Respiratory Medicine, J iangmen Central Hospital, J iangmen 529030, Chin)

机构地区：[1]江门市中心医院呼吸内科,529030 [2]江门市中心医院病理科,529030 [3]江门市中心医院检验科,529030 [4]江门市中心医院中心实验室,529030 [5]五邑中医院呼吸科,江门529030

出　　处：《国际呼吸杂志》2018年第8期594-601,共8页International Journal of Respiration

基　　金：广东省公益研究与能力建设专项资金项目（2014A020212377）

摘　　要：目的 观察罗格列酮对气管内滴注脂多糖联合香烟烟雾暴露模型大鼠气道重塑过程的保护作用.方法 利用气管内滴注脂多糖联合香烟烟熏法,在SPF级成年雄性Wistar大鼠中构建慢性阻塞性肺疾病（COPD）模型,实验组每天分别以0.1、0.15、0.2 mg/kg罗格列酮灌胃,共30 d;模型组和健康对照组则给予生理盐水,其中健康对照组为正常培养的非建模大鼠.实验结束后处死所有大鼠,取右肺进行苏木精-伊红染色、改良Gordon-Sweets染色和Masson染色,并对切片进行气道病理病变评分和胶原沉积厚度测量.取大鼠左肺做肺组织匀浆标本,用酶联免疫吸附法检测肺组织匀浆中磷酸酶和张力蛋白同源基因（PTEN）和转化生长因子β1（TGF-β1）的含量,并对右肺切片进行针对Akt、p-Akt、p-Smad1/5和p-Smad2/3的免疫组织化学染色.结果 相对于健康对照组,模型组可见明显的肺气肿病理改变;Masson染色见大量蓝绿色胶原纤维,呈片状或束状沉积,肌层明显增厚;网状纤维染色见大量棕黑色网状纤维沉积.给予梯度浓度的各罗格列酮组上述病理改变较模型组轻.相对于健康对照组,模型组大鼠肺组织匀浆中 TGF-β1的含量均显著升高,给予梯度浓度的罗格列酮能显著降低TGF-β1水平.相对于健康对照组,模型组大鼠肺组织中 Akt、p-Akt和p-Smad2/3均显著升高,给予梯度浓度的罗格列酮后,p-Akt和p-Smad2/3下降,但Akt和p-Smad1/5不受影响.结论 罗格列酮能通过同时抑制Akt信号通路及TGF-β1信号通路,抑制胶原过度沉积,从而减轻肺实质的损伤程度,抑制气道重塑,延缓CO PD的进程.Objective To investigate the protection of rosiglitazone against the airway remodeling in airway-instillation-lipopolysaccharide and smoke-induced rat models.Methods Chronic obstructive pulmonary disease （COPD） models were established by exposure of airway-instillation-lipopolysaccharide and smoking on specific pathogen free grown male Wistar rats.They were divided into five groups, including normal group,model control group and three treatment groups.The treatment groups were everyday received with 0.1 mg/kg,0.15 mg/kg,and 0.2 mg/kg rosiglitazone for 30 days respectively. The normal group and model control group were received with normal saline,and the normal group was cultured without COPD modeling treatment.All rats were sacrificed after treatment or normal culture for 30 days.The right lung tissue sections were stained by hematoxylin and eosin staining,Gordon-Sweets staining,and Masson staining.The pathologic grading of airway and collagen deposition thickness were measured by pathologists.The levels of phosphatase and tensin homolog （PTEN） and transforming growth factor-β1（TGF-β1） were examined in homogenate sample from left lung by enzyme linked immunosorbent assay.The protein levels of Akt,p-Akt,p-Smad1/5 and p-Smad2/3 were detected by immunohistochemistry.Results Compared with normal group,the emphysema was observed in lung of rats,numerous blue and green collagen fibers were deposited as schistous or sarciniform structure and the muscular layer was obviously thickened by Masson staining,a large amount of brownish black reticular collagen deposition was observed by reticular fiber staining in model control group.After treatment with rosiglitazone,the pathological changes mentioned above were relieved compared with model control group. Compared with normal group,the levels of TGF-β1,Akt,p-Akt,and p-Smad2/3 in the lung homogenate of rats were dramatically elevated in model control group,which were deterrent after treated with rosiglitazone expect for Akt and p-Smad1/5.Conclusions Rosiglitazon

关 键 词：慢性阻塞性肺疾病 罗格列酮 气道重塑 

分 类 号：R-332[医药卫生] R563.9