经鼻滴入博莱霉素致小鼠肺纤维化模型的建立及其病理演变

Establishment and Pathological Evolution of a Mouse Model of Pulmonary Fibrosis by Nasal Bleomycin Instillation

目的经鼻快速滴入博莱霉素复制小鼠肺纤维化模型,观察肺纤维化模型小鼠的病理形态学改变及其羟脯氨酸含量变化,鉴定肺纤维化模型的成功建立。方法经鼻滴入博莱霉素建立小鼠肺纤维化模型。分别于造模第14天和第28天后,取肺组织行HE染色和天狼猩红染色,取心、肝、脾、肾、脑组织行HE染色,光镜下观察组织病理学变化;造模第28天后用样本碱水解法检测肺组织中羟脯氨酸(HYP)的含量。结果①肺组织病理形态学改变:造模第14天和第28天后模型组小鼠肺泡炎及纤维化程度均明显高于阴性对照组,并且在造模第28天后肺纤维化程度进一步加重;②肺组织中HYP含量:与阴性对照组比较,模型组显著升高(P<0.05)。结论经鼻滴入博莱霉素可以成功复制小鼠肺纤维化模型,肺纤维化模型小鼠HYP含量升高。

Objective To establish a mouse model of pulmonary fibrosis by nasal instillation of bleomycin（BLM） and evaluate the model by histopathology and measure the content of oxyproline in the lung tissues.Methods BLM was instilled into the nasal cavity.After 14 and 28 days,lung tissue samples were examined by histopathology using HE and sirius red staining.The heart,liver,spleen,kidney and brain tissues were examined by histopathalopy.At the 28th day,the TGF-β_1 content of the bronchoalveolar lavage fluid（BALF） was tested by enzyme linked immunosorbent assay,and hydroxyproline（HYP） was assessed by alkaline hydrolysis.Results（1） Histopathology： The degree of air alveolitis and fibrosis in the model group was obviously higher than that in the negative control group and the degree of pulmonary fibrosis was increased on the 14（th） and 28th day;（2） HYP content in lung tissue： Compared with the normal group,HYP content in the model group was significantly increased（P0.05）;（3） TGF-β_（1） content in BALF： Compared with the normal group,TGF-β_1 in the model group was significantly increased（P0.05）.Conclusion A mouse model of pulmonary fibrosis has been successfully established by nasal BLM instillation.Both HYP and TGF-β_1 contents are increased in the model mice.