孕鼠体内高胆酸水平对胎鼠心肌组织的影响

Effects of maternal hypercholanemia on fetal myocardium in rats

目的初步探讨孕鼠高胆酸环境对胎鼠心脏结构的影响。方法选择清洁级雌性SD大鼠30只，随机分成3组，每组各10只。妊娠第13-20天，A组孕鼠每天腹腔内注射胆酸溶液5．5mg／（kg·d）（高胆酸组），B组注射胆酸溶液1．4rag／（kg·d）（低胆酸组），C组注射生理盐水1ml（对照组）。3组孕鼠均于孕第21天处死，测定母胎血中总胆汁酸（total bileacid，TBA）和心肌肌钙蛋白I（cardiac troponin I，cTnI）的浓度。取胎鼠的心脏组织，分别行光镜和电镜观察心肌细胞的改变。结果（1）三组孕鼠和胎鼠血TBA浓度分别A组（22．32±8．12）μmol／L，（28．84±8．06）μmol／L；B组为（9．77±3．56）μmol／L，（9．34±3．54）μmol／L；C组为（3．60±1．78）μmol／L，（3．95±1．19）μmol／L。三组间分别进行母鼠和胎鼠的两两比较差异均有统计学意义（P〈O．01）。（2）胎鼠死胎率在A、B、C三组中分别是30．11％，16．85％，7．05％，两两比较有统计学意义（P〈o．05）。（3）A组胎鼠的cTnI值为（19．98±7．75）ng／ml；B组（11．41±3．64）ng／ml；C组（4．38±1．19）ng／ml，两两比较有统计学意义（P〈O．01）。（4）光镜下胎鼠心肌病变积分：A组为1．92±0．43，B组为1．36±0．37，C组为0．44±0．12。两两比较有统计学意义（P〈0．01）。（5）电镜下胎鼠心肌细胞中，A组线粒体的数密度比C组小（P〈0．05），而平均体积比C组大（P〈O．05）。B组线粒体的平均体积比C组大（P〈O．05），但数密度与C组相比无差异。A组胎鼠肌原纤维的数密度和平均体积均比C组小（P〈O．05）。B组胎鼠肌原纤维的数密度比C组小（P〈0．05），平均体积无差异。（6）母血TBA、胎鼠TBA、胎血cTnI值及胎鼠心肌病变积分之间两两比较均呈正相关（P＜0．01）。结论孕鼠体内高胆酸水平对胎鼠心肌组织损伤明显，孕鼠体内高胆酸可造成胎鼠心肌组织损伤，胎鼠血清cTnI与TBA呈正相关。

Objective To explore the effects of maternal hypercholanemia on the myocardium changes in rat fetus. Methods Thirty clean SD female rats were equally randomized to three groups after mating successfully. From the 13th to 20th day of gestation, group A and B were injected intraperitoneally with bile acid of 5.5 mg/（kg·d） and 1.4 mg/（kg·d）, respectively. Group C were injected with sodium chloride（NS） as control. Total bile acid（TBA） and cardiac troponin I（cTnI） were measured in the maternal and fetal serum on the 21st day when all rats were killed. Fetal cardiac muscle cells were also collected for examination with light microscope and electronic microscope. Results （1） TBA in maternal and fetal serum were （22.32 ±8.12）μmol/L and （28.84 ±8.06） μmol/L, respectively in group A, （9.77±3.56） μmol/L and （9.34±3.54） μmol/L in group B, and （3.60±1.78）μmol/L and （3.95±1.19） μmol/L in group C. Significant differences were found among groups （P〈0.01）. （2） Fetal death rates were significantly different among the three groups （P〈0.05）, with 30.11%, 16.85%, and 7.05%, respectively. （3） Fetal cTnI were also found significant difference among groups （P（0.01）, with （19.98±7.75） ng/ml, （11.41±3.64） ng/ml and （4.38±1.19） ng/ml, respectively. （4） The integrated scores of fetal necrosis area were significantly different in three groups （P〈0.05）, with 1.92±0.43, 1.36±0.37 and 0. 44±0.12, respectively. （5） Under electronic microscope, the number density of mitochondria in group A was lower than that in group C （P〈0.05） while the average volume of mitochondria was larger in group A （P〈0.05）. The average volume of mitochondria in group B was larger than that in group C （P〈0.05） while no difference was found with regard to the number density between the two groups. The number density and average volume of myofibril in group A were lower than those in group C （P〈0.05）. The number density of myofibril in group B was higher than that in group C （P〈0.05） while no difference was found with the average volume. （6） Positive correlations were found in maternal TBA, fetal TBA, fetal cTnI and the integrate of fetal necrosis area when comparing every two of the above factors. Conclusions Fetal myocardium is impaired obviously in hypereholanemia rats. The serum level of TBA and eTnI in fetal rats are positively correlated with each other.