Induction of preeclamptic rat model by injection of ultra-low-dose lipopolysaccharide in early pregnancy / 中华围产医学杂志

ABSTRACT

Objective To establish an animal model of preeclampsia by injecting ultra-low-dose lipopolysaccharide (LPS) to rats in early pregnancy,and to lay the foundation for further study on mechanisms of preeclampsia.Methods Twenty-four pregnant rats were divided into six groups according to the random number table and were injected with LPS 0.3,0.5,0.7,1.0,2.0 μg/kg or saline 2 ml respectively through tail veins on day 5 of pregnancy.The differences in blood pressure,urinary protein and pathological changes in placenta among groups were compared to confirm the suitable dose of LPS for establishing preeclamptic model.Then another 19 pregnant rats were injected with the chosen dose of LPS slowly through tail veins on day 5 of pregnancy; 15 of which were chosen as model group; the other four were chosen as postpartum group.Three non-pregnant rats were as non-pregnant group.Besides,another 15 pregnant rats were injected with saline as pregnant control group.Systolic blood pressure,urinary protein excretion,placental weight,fetal weight,serum white blood cell counts,blood platelet counts,plasma anti-thrombin-Ⅲ content,D-dimer content were examined and compared among groups with one way analysis of variance; histopathologic studies were also done on the placentas,kidneys and aortas of the rats.Results (1) Placental weight of LPS 0.3 μg/kg group increased compared with control group.One pregnant rats(1/4) in LPS 1.0 μg/kg group and LPS 2.0 μg/kg group died on day 16 of pregnancy as a result of vaginal bleeding.Systolic blood pressure of LPS 0.5 μg/kg group rose steadily,while no significant changes were found in other groups.Urinary protein increased in all LPS groups,while urinary protein of LPS 0.7 μg/kg group and LPS 1.0 μg/kg group peaked on day 12 of pregnancy and then decreased; urinary protein of LPS 0.5 μg/kg group increased most significantly,and fetus in LPS 0.5,0.7 and 2.0 μg/kg groups had lighter body weight.So LPS 0.5 μg/kg was chosen as the suitable dose to establish preeclamptic model.(2)Compared with pregnant control group,model group had higher systolic blood pressure [(124.89±1.79) mm Hg vs (119.02±1.80) mm Hg,LSD test,P=0.03] from day 6 of pregnancy,more urinary protein [(2.02±0.29) mg vs (1.11±0.18) mg,LSD test,P=0.00] from day 9 of pregnancy,more absorbed embryos [3.6％ (7/194) vs 0.0％ (0/200),Fisher exact test,P=0.01] at day 20 of pregnancy,higher incidence of placenta bleeding [4.1％ (8/194) vs 0.0％ (0/200),Fisher exact test,P=0.00] and fetal growth restriction [13.9％ (27/194) vs 6.0％ (12/200),X2=6.92,Fisher exacttest,P=0.01].Model group showed more inflammatory cells infiltration in the placenta,more glomerular mesangial cells,swelling and desquamated of renal tubular epithelial cells compared to control group.Blood pressure and urinary protein of the model group recovered to the baseline at the sixth day of postpartum,and no changes in blood pressure and urinary protein were found in non-pregnant rats.Conclusions Injection of LPS 0.5 μg/kg on day 5 of pregnancy through tail veins could induce the clinical symptoms of preeclampsia in rats,which might be an ideal model for further preeclampsia research.