首页|BAPN诱导小鼠胸主动脉夹层合并急性肺损伤模型的建立

BAPN诱导小鼠胸主动脉夹层合并急性肺损伤模型的建立

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目的 采用β-氨基丙腈(β-aminopropionitrile monofumarate,BAPN)1 g/(kg·d)饮水给药的方式,构建一种可行性高、稳定的胸主动脉夹层(thoracic aortic dissection,TAD)合并急性肺损伤(acute lung injury,ALI)的小鼠模型,为研究TAD合并ALI提供合理的动物模型.方法 选取45只SPF级3周龄C57BL/6J雄性小鼠,随机分为CON组15只(正常饮食水)和BAPN组30只(与无菌水配置成1 g/(kg·d)的溶液饮水给药),持续4周.实验期间,观察两组小鼠一般情况、成模率,通过测量小鼠胸主动脉最大直径和主动脉组织苏木素-伊红(HE)染色,验证小鼠TAD模型并将BAPN组分为TAD组和Non-TAD组.进一步检测CON组、Non-TAD组和TAD组小鼠肺组织 HE 病理染色、湿干重比(dry/wet weight ratio,W/D)及肺泡灌洗液(broncho alveolar lavage fluid,BALF)中总蛋白水平和白细胞介素-1β(interleukin-1β,IL-1β)、白介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)表达情况验证小鼠TAD合并ALI模型.结果 BAPN干预明显延缓小鼠体重和饮水量的增加.与CON组和Non-TAD组相比,TAD组小鼠胸主动脉最大直径明显增粗(P<0.05);主动脉HE染色显示主动脉中层明显增厚,主动脉壁结构破坏、紊乱;肺组织HE染色显示肺间质明显水肿及炎性渗出,伴肺泡腔扩大,肺泡壁上皮脱落及透明膜形成,肺损伤病理评分显著增加(P<0.05);肺组织W/D、BALF中总蛋白水平及IL-1β、IL-6、TNF-α表达也明显升高(P<0.05),而另外两组上述指标无明显差异.结论 通过BAPN饮水给药的方式,可成功建立胸主动脉夹层合并急性肺损伤的小鼠模型.
Establishment of a mouse model of thoracic aortic dissection with acute lung injury by BAPN
Objective A feasible and stable mouse model of thoracic aortic dissection(TAD)combined with acute lung injury(ALI)was established using β-aminopropionitrile monofumarate(BAPN)1 g/(kg·d)administered in drinking water.The mouse model of TAD combined with acute lung injury(ALI)was established to provide a rational animal model to study TAD combined with ALI.Methods Forty-five SPF-grade 3-week-old C57BL/6J male mice were selected and randomly allocated to a CON group(normal dietary water;15 mice)or BAPN group(administration in sterile water at 1 g/(kg·d);30 mice)for 4 weeks.During the experimental period,the general condition and modeling rate of mice were observed.TAD model mice were validated,and the BAPN group was divided into TAD and non-TAD groups by measuring the maximum diameter of the thoracic aorta and HE staining of aortic tissues.HE pathological staining,the wet/dry weight(W/D)ratio,total protein level in bronchioalveolar lavage fluid(BALF),and interleukin(IL)-1 β,IL-6,and tumor necrosis factor-α(TNF-α)in BALF)were used to validate the TAD combined ALI model in mice.Results BAPN treatment significantly delayed the increase in body mass and water intake of mice.Compared with CON and non-TAD groups,the maximum diameter of the thoracic aorta of mice in the TAD group was significantly thickened(P<0.05).HE staining of the aorta showed significant thickening of the middle aortic layer,and the structure of the aortic wall was damaged and disordered.HE staining of lung tissues showed significant interstitial edema and inflammatory exudation accompanied by enlargement of alveolar lumen,alveolar wall epithelial exfoliation and hyaline membrane formation,and a significant increase in the pathological scores of lung injury(P<0.05).Total protein levels and expression of IL-1β,IL-6,and TNF-α in lung tissue,W/D ratio,and BALF were also significantly increased(P<0.05),whereas no significant difference was observed in the above indexes between the other two groups.Conclusions A mouse model of thoracic aortic dissection combined with acute lung injury can be established by BAPN administration in drinking water.

β-aminopropionitrile monofumaratethoracic aortic dissectionacute lung injurymice

买志妍、江丽青、朱翰朝、张溧昀、王云、段维勋

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宁夏医科大学临床医学院,银川 750004

宁夏医科大学总医院心脏大血管外科,银川 750004

空军军医大学西京医院心血管外科,西安 710032

β-氨基丙腈 胸主动脉夹层 急性肺损伤 小鼠

国家自然科学基金国家自然科学基金国家自然科学基金宁夏回族自治区科技厅重点研发项目陕西省重点研发计划空军军医大学人才扶持"翱翔计划"项目

8224120482070503822704202021BEG020352022ZDLSF02-012020axjhdwx

2024

中国实验动物学报
中国实验动物学会,中国医学科学院医学实验动物研究所

中国实验动物学报

CSTPCD北大核心
影响因子:0.767
ISSN:1005-4847
年,卷(期):2024.32(1)
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