盐酸氨溴索和倍他米松对大鼠胎肺形态发育影响的对比研究

Comparison of effects the ambroxol and betamethasone administered antenatally on fetal lung morphogenesis in rats

目的探讨产前注射盐酸氨溴索和倍他米松对大鼠胎肺形态发育的影响。方法12只孕鼠随机分成4组:盐酸氨溴索组、倍他米松1d组、3d组及对照组,每组3只大鼠。盐酸氨溴索组、倍他米松3d组从妊娠第16天起分别腹腔注射3d盐酸氨溴索100mg/(kg·d)、倍他米松0·2mg/(kg·d);倍他米松1d组在妊娠第16、17天注射生理盐水,第18天注射倍他米松0·2mg/(kg·d);对照组在同样时间连续3d注射生理盐水。在妊娠第19天将孕鼠处死后立即剖腹取仔鼠,每只孕鼠取6只胎鼠肺组织,通过光镜观察、图像分析及电镜技术比较2种药物、不同疗程对孕鼠的胎仔肺组织形态结构影响。结果光镜下各治疗组与对照组相比肺泡间隔薄(P<0·001),呼吸膜周径及肺泡表面积均增大(P<0·05),以倍他米松3d组改变最为明显(P<0·001)。倍他米松1d组较盐酸氨溴索组肺泡间隔薄,呼吸膜周径大(P<0·05)。倍他米松3d组较1d组肺泡间隔薄,呼吸膜周径及肺泡表面积大(P<0·001)。透射电镜下治疗组肺泡Ⅱ型上皮内可见板层小体,细胞器多见,以倍他米松3d组改变最为明显,而对照组内未见板层小体,细胞器少见。结论产前注射盐酸氨溴索、倍他米松均能显著促进胎肺发育,倍他米松重复给药效果优于单次,倍他米松疗效优于盐酸氨溴索。

Objective To compare the effects of administering ambroxol and betamethasone administered antenatally on fetal lung morphogenesis in rats. Methods Twelve pregnant rats were randomly assigned into 4 groups （n = 3 ）, ambroxol group, 1-day betamethasone group, 3-day betamethasone group and control group. The rats in the ambroxol group and 3-day betamethasone group were given ambroxol 100 mg/（ kg. d） or betamethasone 0. 2 mg/（ kg. d） intra-peritoneally for 3 days sence the 16^th day of gestational age. The rats in 1-day betamethasone group were given normal saline on 16^th and 17^th day of gestation, betamethasone 0. 2 mg/（ kg· d） on the 18^th day of gestation. The rats in control group were given normal saline for 3 consecutive days of the same gestational age. The rats were sacrificed on the 19^th day of gestation and embryos were harvested via cesareans. The histology of 6 fetal lungs of each pregnant rats were observed with light microscope, transmission electron microscope and image analysis. Results Compared with control group, fetal rat lungs in treatment groups had thinner alveolar walls （ P 〈 0. 001 ）, larger alveolar space and respiratory thecal perimeter （ P 〈 0. 05 ）, especial for 3-day betamethasone group （P 〈 0. 001 ）. Compared with ambroxol group, fetal lungs in 1-day betamethasone group had thinner alveolar walls and larger resoiratorv thecal oerimeter （ P 〈 0. 05 ）. Fetal lungs of rats with repeat injections of betamethasone had larger pulmonary alveoli, respiratory thecal perimeter and thinner alveolar septum than that of the single dose treated animals （ P 〈 0. 001 ）. Under transmission electron microscopy, lamellar body and cellular organs in endochylema of type Ⅱ alveolar cell of the treatment groups were more common compared with the control group. Obvious changes were found in triple doses betamethasone group. Conclusion Ambroxol and betamethasone could promote the development of fetal lungs, triple doses of betamethasone has prior effects to single dose of betamethasone; single dose betamethasone is better than ambroxol.