气管滴注大气细颗粒物构建大鼠慢性阻塞性肺疾病模型  

A rat model of chronic obstructive pulmonary disease is constructed by intratracheal administration of fine particulate matter

作　　者：王荣[1] 李嘉瑞 曹珊珊 廉婷 刘蓓 岳晨星 王娜娜[1] 秦蓓[1] WANG Rong;LI Jia-rui;CAO Shan-shan;LIAN Ting;LIU Bei;YUE Chen-xing;WANG Na-na;QIN Bei(Department of Pharmacy,Xi'an Medical University,Xi'an 710021,China;College of Clinical Medicine,Xi'an Medical University,Xi'an 710021,China;Department of Medical Technology,Xi'an Medical University,Xi'an 710021,China)

机构地区：[1]西安医学院药学院,陕西西安710021 [2]西安医学院临床医学院,陕西西安710021 [3]西安医学院医学技术学院,陕西西安710021

出　　处：《中国病理生理杂志》2022年第4期665-671,共7页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81903288);西安医学院校级科技创新团队(No.2021TD03);陕西省重点产业创新链群项目(No.2021ZDLSF03-05)。

摘　　要：目的:采用气管滴注大气细颗粒物(PM_(2.5))建立慢性阻塞性肺疾病(COPD)肺功能损伤大鼠模型,并对该模型进行评价。方法:SD大鼠随机分为正常对照组、2.5 mg/kg PM_(2.5)组、5 mg/kg PM_(2.5)组和10 mg/kg PM_(2.5)组。按1 mL/kg气管滴注PM_(2.5)溶液,连续5次。采用小动物呼吸肺功能测量系统测定大鼠肺功能;ELISA法测定大鼠血清中炎症指标;收集大鼠支气管肺泡灌洗液(BALF),对BALF进行涂片和染色,对炎症细胞进行分类和计数;检测肺组织匀浆中谷胱甘肽过氧化物酶(GSH-Px)活性和丙二醛(MDA)含量;通过HE、Masson和弹性纤维染色检测各组大鼠肺组织病理变化。结果:PM_(2.5)滴注对大鼠体重无显著影响,可引起大鼠呼吸频率和呼吸指数增加(P<0.05),降低最大吸气流速和肺动态顺应性(P<0.05)。PM_(2.5)滴注可引起大鼠血清中肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-β)和IL-6含量显著增高(P<0.05),大鼠BALF中白细胞和单核细胞比值显著升高(P<0.05,P<0.01),嗜酸性粒细胞比值降低(P<0.01)。PM_(2.5)滴注可显著降低大鼠肺组织匀浆中GSH-Px活性(P<0.05)。PM_(2.5)滴注可引起大鼠气道管腔变形、炎症细胞浸润、胶原纤维和弹性纤维表达增加,在巨噬细胞内可观察到PM_(2.5)颗粒。结论:PM_(2.5)气管滴注可成功构建大鼠COPD肺功能损伤模型。AIM:To establish a rat model of lung function injury of chronic obstructive pulmonary disease(COPD)by using intratracheal instillation of fine particulate matter(PM_(2.5)).METHODS:SD rats were randomly divid⁃ed into control group and different concentrations(2.5,5 and 10 mg/kg)of PM_(2.5) groups.Rats were intratracheal adminis⁃tration of PM_(2.5) solution at the dose of 1 mL/kg for 5 consecutive times.Lung function of rats was evaluated by a small ani⁃mal ventilator research system.Serum inflammatory factors were measured by ELISA.The bronchoalveolar lavage fluid(BALF)were collected and the inflammatory cells were counted.The activity of glutathione peroxidase(GSH-Px)and the conent of malondialdehyde(MDA)in lung tissues were determined.Morphologic changes of lung were observed by HE,Masson and elastic fiber staining.RESULTS:Intratracheal administration of PM_(2.5) did not affect the weight of rats.PM_(2.5) increased frequency and respiratory index(P<0.05),decreased peak inspiratory flow and pulmonary dynamic com⁃pliance(P<0.05).PM_(2.5) significantly increased the serum levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6(P<0.05)and the ratio of leukocyte and monocyte(P<0.05 or P<0.01),but decreased the eosinophil ratio(P<0.01).The activity of GSH-Px in lung tissue was also significantly decreased after PM_(2.5) inhalation(P<0.05).Intratracheal administration of PM_(2.5) caused airway stenosis and inflammatory cell infiltration.The expression of collagen fibers and elastic fibers were significantly increased.PM_(2.5) particles were observed in macrophages.CONCLUSION:Intratra⁃cheal instillation of PM_(2.5) induces lung function injury of COPD in rats.

关 键 词：细颗粒物 慢性阻塞性肺疾病 气管滴注 炎症 氧化应激 

分 类 号：R563.2[医药卫生—呼吸系统] R363.2[医药卫生—内科学]