SD大鼠肺气肿模型的建立及全反式维甲酸干预作用探讨

目的观察不同浓度的全反式维甲酸(all-transretinoicacid,ATRA)对猪胰蛋白酶复制的大鼠肺气肿模型的治疗作用。方法建立猪胰蛋白酶(porcine pancreatic elastase,PPE)复制的大鼠肺气肿模型,将体重170~220 g的60只SD大鼠随机分为生理盐水对照组(N)、模型组(P)、小剂量ATRA治疗组(R1)、中剂量ATRA治疗组(R2)、大剂量AT-RA治疗组(R3)、棉籽油组(C)各10只。后5组向大鼠气管内滴注1U·g-1PPE,N组同样滴注等量生理盐水,饲养76d,治疗组和棉籽油组分别向大鼠腹腔内连续注入大、中、小剂量ATRA和棉籽油14 d。测量干预前后的大鼠肺体积,血气分析和病理形态学图像分析了解不同浓度ATRA对于PPE复制的大鼠肺气肿模型的治疗效果。结果R1、R2、R3组、P组、C组的大鼠肺体积明显大于N组(P<0.01),C组和P组的肺体积无差异,各治疗组的肺体积较P组有差异,各治疗组之间的肺体积无差异。肺泡形态学结果显示R1、R2、R3组、P组、C组与N组比较,每个视野内的肺泡数(Na)明显减少,平均肺泡面积(MAA)增大,平均内衬间隔(MLI)较大,差异有显著性(P<0.05);R1、R2组相对于P组Na增加,MAA减少,差异有统计学意义,但两组之间无差别;R3组、C组和P组的各指标无明显差别。血气分析结果P组、R1、R2、R3组和C组的二氧化碳分压(PaCO2)比N组升高,P组、C组和R3组的氧分压(PaO2)、氧饱和度(SaO2)值明显低于N组,R1、R2组的PaO2、SaO2值与N组无差异,与P组也无差异。结论中、低剂量组的ATRA对肺气肿模型的治疗在肺泡修复上明显效果,但肺功能的改善不明显;大剂量组ATRA治疗后效果不明显。

Constructing the SD rat models of chronic obstructive pulmonary emphysema and effects of treatment by all-transretinoic Acid

Aim To evaluate effects of the all-transretinoic acid(ATRA) with different concentrations on alveolar repair and pulmonary function in emphysema rats.Methods The body weights between 170 and 220 g,male Sprague-Dawley(SD) rats were randomly divided into controls group(N,n=10),emphysema group(P,n=10),low-dose ATRA treatment group(R1,n=10),middle-dose ATRA treatment group(R2,n=10),high-dose ATRA treatment group(R3,n=10)and cottonseed oil group(C,n=10).In addition to N group,the rat models of emphysema were constructed by a single intratrachcal instillation of porcine pancreatic elastase(PPE) to rats.The ATRA treatment groups and cottonseed oil groups were separately treated with ATRA(500 μg·kg-1,1000 μg·kg-1,2000 μg·kg-1)and cottonseed oil,intraperitoneally daily for 2 weeks.After the emphysema models were constructed,the analysis of artery blood gas and alveolar morphometry of rats was performed.Experimental results were compared among normal group,model group,cottonseeds oil and ATRA treatment groups.Results The lung volumes and the pathological semi-quantitive analyses of the P,C and three treatment groups were significantly different from N group(P<0.01).For lung volumes,no statistical significance was observed between the C group and the P group,while the lung volumes of the three treatment group were smaller than those of the P group,but there was no difference between the three treatment groups.The pathological semi-quantitive analyses were significantly different among the R1 group、the R2 treatment group and the P group(P<0.05).However,for the pathological semi-quantitive analyses of the R3 treatment group,the C group and the P group,no statistical significance could be observed(P>0.05).Moreover,there were no significant changes in artery blood gas analysis.Conclusion The low-dose and middle-dose ATRA treatment might significantly promote alveolar repair and remedy pulmonary malfunction,with little effects on artery blood gas analysis in emphysematous rats.However,no positive effect was observed for high-dose ATRA treatment group.