The Establishment Of Preeclampsia Models And The Effect Of MDSC And Its Primary Mechanism In Preeclampsia

Objective: Preeclampsia(PE) is a common pregnancy complication. The incidence of this complication is- about 2%-8%. PE seriously affects maternal and fetal mortality and morbidity. Therefore, the pathogenesis of preeclampsia is always the focus of scientist research. Aberrant maternal immune responses play an important role in the development of PE. Systemic immune cell activation may be one of the main causes for the pathogenesis of PE. Myeloid derived suppressor cell(MDSC) is a kind of myeloid suppressor cells, characterized by their ability to modulate T cell responses during pregnancy. But its roles in PE are rarely studied. The purpose of the present study is to establish the mice model of PE by exogenously administration of different substance and facilitate to investigate the pathogenesis of preeclampsia. Observing the apoptosis alteration of spleen cells in PE model and firstly proposing that MDSC may play an important role in the pathogenesis of preeclampsia.Methods:1. Pregnant mice were intraperitoneally(i.p.) injected with 0.35mg/kg Cd Cl2 on day 12 to day 15 of pregnancy. Blood pressure and urinary protein in mouse modelwere measured. The fetus, placenta and the spleen were weighted. The morphology of the placenta and kidney were observed.2. Pregnant mice were i.p. injected with 14μg/kg LPS on day 12 of pregnancy and56μg/kg LPS on day 13 to 15 of pregnancy. Blood pressure and urinary protein in mouse modelwere measured. The fetus, placenta and the spleen were weighted. The morphology of the placenta and kidney were observed.3. Apoptosis morphology of splenocytes were measured by TUNEL and the protein levels of Bcl-2 and Bax were detected by western blotting.in the spleen of normal pregnant mice and PE model mice.4. The percentage of the splenic MDSC by flow cytometry in normal pregnant mice and preeclampsia model mice.Results:1. After pregnant mice were i.p, injected with low dose Cd Cl2 and LPS i blood pressure and urinary protein were increased and their weigh of placenta and fetal decreased compared with normal pregnant mice. All of model mice developed clinical symptoms of preeclampsia2. After pregnant mice were i.p, injected with low dose Cd Cl2 and LPS, the spleen enlarge and the number of apoptotic cells were decreased. The protein expression of Bcl-2 was increased and the protein expression of Bax was decreased.3. Compare to no pregnant mice, the percentage of MDSCs in spleen of normal pregnant mice were increased, however, the percentage of MDSCs were highly increased in spleen of preeclampsia model mice with low dose LPS stimulationConclusion:1. Preeclampsia mouse model can be established by the administration of low dose Cd Cl2 and LPS. The model is reproducible and is a good simulation of clinical symptoms the preeclampsia. It is a good model to investigate the pathogenesis of preeclampsia.2. The number of splenic apoptosis cells were decreased and immune cells were activated.in the spleen of pregnant mice after the stimulation of low dose Cd Cl2 and LPS.3. As a kind of immune suppressor cells, the expansion of MDSCs in the spleen of preeclampsia model mice may indicate an important role of MDSCs in materno-fetal tolerance.