博来霉素和内毒素诱导两种品系小鼠肺纤维化模型的比较研究

Comparative Study on Pulmonary Fibrosis Model Induced by Bleomycin and Endotoxin in Two Strains of Mice

目的通过比较博来霉素和内毒素诱导ICR、C57BL/6两个品系小鼠的肺纤维化程度,从而建立合适的小鼠肺纤维化模型。方法分别将ICR、C57BL/6两个品系小鼠随机分为对照组、博来霉素组、内毒素组。博来霉素组向气管注射博来霉素(5 mg/kg体质量),内毒素组尾静脉注射内毒素(40 EU/kg体质量),对照组气管注射等量生理盐水。两个品系的对照组、博来霉素组、内毒素组分别于造模后第7、14、28天各处死8只,观察小鼠一般情况,测量小鼠肺系数;采用HE染色观察肺组织病理学变化;ELISA法检测肺组织中羟脯氨酸的含量。结果与对照组相比,两个品系的博来霉素组和内毒素组的肺系数、肺组织羟脯氨酸含量均不同程度增加,有显著性差异(P<0.05)。其中对于同一种肺纤维化诱导剂,C57BL/6品系小鼠的肺系数、肺组织羟脯氨酸含量与ICR品系小鼠相比,有显著性差异(P<0.05)。对于同一品系小鼠,博来霉素组在不同时间点的肺系数、肺组织羟脯氨酸含量和内毒素组相比,无显著性差异(P>0.05)。结论C57BL/6小鼠对博来霉素和内毒素更敏感。博来霉素、内毒素均能够制备小鼠急性肺损伤肺纤维化模型。

Objective A suitable mice pulmonary fibrosis model was established by comparing the degree of pulmonary fibrosis induced by bleomycin and endotoxin in two strains of ICR and C57 BL/6 mice.Method Two strains of ICR and C57 BL/6 mice were randomly divided into control group,bleomycin group and endotoxin group,respectively.The bleomycin group received a single intratracheal instillation of 5 mg/kg body weight of BLM to induce pulmonary fibrosis,the endotoxin group was Intravenously injected with endotoxin of 40 EU/kg,while normal control groups were administrated the same amount of normal saline.On the 7 th,14 th and 28 th day,8 mice were respectively sacrificed in each model group.The general condition of the mice was observed,and the lung coefficient of the mice was measured.The pathological changes of the lung tissues were observed by HE staining.The content of hydroxyproline in the lung tissues was detected by ELISA.Result Compared to the control group,the lung coefficient and lung hydroxyproline content of each model group increased to different degrees(P<0.05).The lung coefficient,lung hydroxyproline content of the bleomycin group and endotoxin group of C57 BL/6 were significantly different from the bleomycin group and endotoxin group of ICR(P<0.05).The lung coefficient,lung hydroxyproline content of the bleomycin group of C57 BL/6 was no difference from the endotoxin group of C57 BL/6(P>0.05).Conclusion C57 BL/6 mice are more sensitive to bleomycin and endotoxin.Both bleomycin and endotoxin can prepare lung fibrosis models of acute lung injury in mice.