The Effect Of Bile Acid On The Lung Of Fetal Rats

Objective To explore the effect of bile acid on the lung of fetal rats.Methods Forty Sprague-Dawley pregnant rats were randomly devided into four groups A,B,C and D.On day 13 of gestation,group A and B were injected intraperitoneally with bile acid for 8 days.The dose of group A was 5.5 mg·(kg·d)^-1 and the dose of group B was 1.4 mg·(kg·d)^-1.Group C was injected intraperitoneally with Sodium Chloride(NS) for 8 days.No special intervention had been done to group D.Blood was drawn from each pregnant rat before and after bile acid administration to measure the levels of total bile acid(TBA),alanine aminotransferase(ALT),aspartate aminotransferase(AST),tatal bilirubin (TBIL)and direct bilirubin(DBIL).On day 21 of gestation,cesarean section were performed and the morphology of fetal rat lungs were observed with light microscope,electronic microscope and image analysis.The fetal serum levels of TBA were measured,and the concentration of pulmonary surfactant-associated protein A(SP-A) were determined by enzyme linked immunoadsorbent assay(ELISE).The relationship between TBA and SP-A was analyzed.Results(1)There were no significant differences of the maternal serum concentration of ALT,AST,TBIL and DBIL among the group A,B,C and D before and after intervention,P＞0.05.The level of TBA in maternal and fetal serum,the mortality rate of fetal rats,the concentration of SP-A in fetal serum,the width of alveolous mesenchyma of fetal rats of group A(21.09±8.58μmol/L,26.3±11.00μmol/L,18.35%,12.45±4.67ng/ml, 70.21±8.95μm) were higher than those in group B(10.49±3.22μmol/L, 10.73±4.76μmol/L,8.82%,7.33±2.54ng/ml,32.21±4.23μm),P＜0.01,which were significantly higher than those in group C(3.98±2.18μmol/L, 4.08±2.40μmol/L,3.77%,2.71±1.30ng/ml,23.51±2.73μm),P＜0.01. But there was no significant difference between group C and D(3.25±1.69μmol/L,3.63±2.06μmol/L,3.03%,2.80±1.20ng/ml,21.63±1.76μm), P＞0.05.The area of alveolus of fetal rats,the number density and average volum of lamellar body of group A(286.15±26.38μm²,47.98±3.88μm^-3, 12.22±2.89×10^-3μm^-3)were lower than those in group B(717.46±22.07μm²,74.46±3.06μm^-3,23.27±2.43×10^-3μm^-3),P＜0.01,which were lower than those in group C(900.13±15.89μm²,81.30±6.56μm^-3,31.40±2.92×10^-3μm^-3),P＜0.01.But no difference was found between group C and D(915.47±19.50μm²,83.08±6.90μm^-3,31.79±2.41×10^-3μm^-3),P＞0.05.(2)With electron microscope,the number density of mitochondria in typeâ…¡alveolar epithelial cells of group A(20.44±4.99μm^-3) was lower than that in group B(31.46±3.45μm^-3),P＜0.01.But no differences were found between group B,C(32.84±3.17μm^-3) and D(31.11±2.65μm^-3),P＞0.05.The average volum of mitochondria in typeâ…¡alveolar epithelial cells of group A(23.22±2.76×10^-3μm³) was bigger than that in group C(15.02±2.91×10^-3μm^-3),P＜0.01.But no difference was found between group A and B(21.27±2.62×10^-3μm^-3),P＞0.05.But no difference was found between group C and D(14.94±3.12×10^-3μm^-3),P＞0.05.(3)There was significant positive correlation of the levels of TBA in maternal and fetal serum(r=0.882,P＜0.01).There was significant positive correlation between TBA and SP-A(r=0.708,P＜0.01).There was significant negative correlation between TBA and the area of alveolus(r=—0.794,P＜0.01).There was significant negative correlation between the area of alveolus and SP-A(r=—0.734,P＜0.01).There was significant negative correlation between the number density of lamellar body and SP-A(r=—0.701,P＜0.01). Conclusions Pathological changes of pulmonary tissue in fetal rats were correlated with the level of TBA in maternal serum.The serum level of TBA in fetal rats and the ultrastructural alterations of typeâ…¡alveolar epithelial cells were correlated with each other,which were also correlated with the serum level of SP-A in fetal rats.