肺纤维化小鼠肺功能的动态变化

Dynamic changes of lung function in mice with pulmonary fibrosis

目的肺功能检测是临床上评价患者肺纤维化程度的常用指标。文中旨在探讨肺纤维化小鼠肺功能的动态变化以及建立正常昆明小鼠肺功能参数参考值范围。方法SPF级昆明小鼠28只,随机数字表法分为正常对照组和模型组,每组14只,用10%水合氯醛麻醉以后正常对照组仅行气管穿刺,模型组则经气管内穿刺注射博来霉素(5 mg/kg体重),并分别在造模后的第1、2、3、4周末按同样的顺序检测所有小鼠的肺功能各项指标:吸气时间(Ti)、呼气时间(Te)、最大吸气量(PIF)、最大呼气量(PEF)、潮气量(TV)、呼气量(EV)、松弛时间(RT)、每分钟呼气量(MV)、f(呼吸频率)、被迫呼吸间隙(Penh)、50%呼气流速(EF50)。结果小鼠气管内注射BLM后,模型组小鼠出现毛发柔顺度降低、掉毛,第2周以后活动程度下降等现象。与对照组相比,模型组Ti、Te和RT值在第4周时明显升高(P<0.05);而第4周PEF、RT、MV、f和EF50值明显下降(P<0.05)。与模型组第1周相比,组内Ti、Te、RT、f值在第2、3、4周时的差异有统计学意义(P<0.05),而MV和EF50值在第3、4周时的差异有统计学意义(P<0.05),PIF值则仅在第4周时存在差异(P<0.01)。与对照组第2、3、4周Penh(0.553±0.189、0.662±0.164、0.712±0.189)比较,模型组(0.820±0.205、0.936±0.188、1.053±0.236)显著升高(P<0.01);与模型组第1周相比,模型组Penh值仅在第3、4周时的差异有统计学意义(P<0.05)。4周的肺功能主要指标Penh值的正常值范围为0.27~0.88。结论运用无束缚全身体积描记系统检测肺功能稳定可靠,效果良好;BLM诱导的肺纤维化小鼠模型在4周内肺功能持续下降;反映气道阻力的Penh在造模第2周后可以进行试验小鼠肺功能的总体筛选。

Objective Pulmonary function testing is a commonly used indicator for clinical evaluation of the degree of pul-monary fibrosis in patients.This paper aims to investigate the dynamic changes of lung function in mice with pulmonary fibrosis and to establish a range of reference values for lung function parameters in normal Kunming mice.Methods Twenty-eight SPF Kunming mice were randomly divided into normal control group(n=14)and model group(n=14).After anesthesia with 10%chloral hydrate,the normal control group only underwent tracheal puncture.The model group received intratracheal puncture and injection of bleomycin(BLM)(5 mg/kg body weight),and the lung function indicators of all mice were detected in the same order on the 1 st,2 nd,3 rd and 4 th weekends after modeling:Ti,Te,PIF,PEF,TV,EV,RT,MV,f,Penh and EF50.Results After intratracheal BLM injection,mice in the model group showed decreased hair softness and smoothness,hair loss and decreased activity after the 2 nd week.Compared with the control group,Ti,Te and RT values in the model group signifi-cantly increased at week 4(P<0.05),while the values of PEF,RT,MV,f and EF50 decreased significantly at the same week(P<0.05).Compared with the model group at week 1,the differences in Ti,Te,RT and f values at week 2,3 and 4 were statistically significant(P<0.05);the differences in MV and EF50 values at week 3 and4 were statistically significant(P<0.05);while the PIF values only showed differences at week 4(P<0.001).Compared with the Penh values in the control group at week 2,3 and 4(0.553±0.189,0.662±0.164,0.712±0.189),the differences of the model group(0.820±0.205,0.936±0.188,1.053±0.236)showed statistical significance(P<0.001).Compared with the model group at week 1,the differences of Penh values in the model group only showed statistical significance at week 3 and 4(P<0.05).Through four-week lung function test,various parameters were obtained,among which the normal range of the main index Penh value was 0.27-0.88.Conclusion The lung function detected by the non-invasive whole body plethysmography system was stable and reliable with good ef-fects;the lung function in mice with the BLM-induced pulmonary fibrosis continued to decrease within four weeks.Penh,which re-flects airway resistance,can be used for overall screening of the lung function among the test mice after two weeks of modeling.