Xiang Q Q, Yang Z, Huai J, Wang G J
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
Zhonghua Fu Chan Ke Za Zhi. 2019 Sep 25;54(9):601-607. doi: 10.3760/cma.j.issn.0529-567x.2019.09.005.
To explore the pathways of preeclampsia by investigating different effects of pravastatin (Pra) on and soluble FMS tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) in different preeclampsia (PE)-like mouse models. C57BL/6J mice were randomly subcutaneously injected with N-nitro-L-arginine methyl ester (L-NAME) or intraperitoneally injected with lipopolysaccharide (LPS) as PE-like mouse model, saline as normal pregnancy control (Con) respectively, daily at gestational 7-18 days. Pra was given daily at gestational 8-18 days in each model group and the mice were divided into Pra (L-NAME+Pra, LPS+Pra, Con+Pra) and saline (L-NAME+NS, LPS+NS, Con+NS) groups. Liver,placental tissue and blood of pregnant mice were collected on the 18th day of pregnancy. The levels of VEGF, PlGF and sFlt-1 in the liver, placenta and serum of mice in each group were compared by western blot, ELISA and real-time fluorescence quantitative PCR (RT-PCR). (1) ELISA: Serum VEGF (205.70±3.43, 154.60±2.31) and PlGF (131.5±3.75, 101.50±4.31) levels were significantly increased in L-NAME+Pra group compared with L-NAME+NS group (all 0.05). Serum VEGF (202.30±4.90, 144.50±6.71) and PlGF (121.50±3.86, 95.41±4.08) levels were significantly higher in LPS+Pra group than those in LPS+NS group (all 0.05). Serum sFlt-1 level in LPS+Pra group was significantly lower than that in LPS+NS group (3.01±0.50, 776.60±80.06), serum sFlt-1 level in L-NAME+Pra group was significantly lower than that in L-NAME+NS group (2.60±0.06, 583.70±9.83; all 0.05). (2) Western blot: the expression levels of PlGF (1.344±0.118, 0.664±0.143) and VEGF (1.34±0.12, 0.66±0.14) in the liver of mice in the L-NAME+Pra group were significantly higher than those in the L-NAME+NS group (all 0.05), but the expression levels of PlGF and VEGF in the placenta of L-NAME+Pra group were not significantly different from those of L-NAME+NS group (all 0.05). The expression levels of PlGF and VEGF in placenta and liver of pregnant mice in LPS+Pra group were not significantly different from those in LPS+N group (all 0.05). (3) RT-PCR: the mRNA expression of PlGF and VEGF in placenta and liver of L-NAME+Pra group were not significantly different from those in L-NAME+NS group (all 0.05). The mRNA expression levels of PlGF and VEGF in placenta and liver of LPS+Pra group were not significantly different from those of LPS+NS group (all 0.05). Pra has different regulatory effects on vascular endothelial function in different PE-like models. It reveals that different pathogenesis and pathways exist in different PE-like changes.
通过研究普伐他汀(Pra)对不同子痫前期(PE)样小鼠模型中可溶性FMS酪氨酸激酶-1(sFlt-1)、胎盘生长因子(PlGF)和血管内皮生长因子(VEGF)的不同影响,探索子痫前期的发病机制。将C57BL/6J小鼠在妊娠第7 - 18天分别随机皮下注射N-硝基-L-精氨酸甲酯(L-NAME)或腹腔注射脂多糖(LPS)建立PE样小鼠模型,以生理盐水注射作为正常妊娠对照(Con)。在每个模型组的妊娠第8 - 18天每日给予Pra,将小鼠分为Pra组(L-NAME + Pra、LPS + Pra、Con + Pra)和生理盐水组(L-NAME + NS、LPS + NS、Con + NS)。在妊娠第18天收集孕鼠的肝脏、胎盘组织和血液。通过蛋白质免疫印迹法(western blot)、酶联免疫吸附测定(ELISA)和实时荧光定量聚合酶链反应(RT-PCR)比较每组小鼠肝脏、胎盘和血清中VEGF、PlGF和sFlt-1的水平。(1)ELISA:与L-NAME + NS组相比,L-NAME + Pra组血清VEGF(205.70±3.43,154.60±2.31)和PlGF(131.5±3.75,101.50±4.31)水平显著升高(均P < 0.05)。与LPS + NS组相比,LPS + Pra组血清VEGF(202.30±4.90,144.50±6.71)和PlGF(121.50±3.86,95.41±4.08)水平显著升高(均P < 0.05)。LPS + Pra组血清sFlt-1水平显著低于LPS + NS组(3.01±0.50,776.60±80.06),L-NAME + Pra组血清sFlt-1水平显著低于L-NAME + NS组(2.60±0.06,583.70±9.83;均P < 0.05)。(2)蛋白质免疫印迹法:L-NAME + Pra组小鼠肝脏中PlGF(1.344±0.118,0.664±0.143)和VEGF(1.34±0.12,0.66±0.14)的表达水平显著高于L-NAME + NS组(均P < 0.05),但L-NAME + Pra组胎盘组织中PlGF和VEGF的表达水平与L-NAME + NS组无显著差异(均P > 0.05)。LPS + Pra组孕鼠胎盘和肝脏中PlGF和VEGF的表达水平与LPS + NS组无显著差异(均P > /span>0.05)。(3)RT-PCR:L-NAME + Pra组胎盘和肝脏中PlGF和VEGF的mRNA表达水平与L-NAME + NS组无显著差异(均P > 0.05)。LPS + Pra组胎盘和肝脏中PlGF和VEGF的mRNA表达水平与LPS + NS组无显著差异(均P > 0.05)。Pra对不同PE样模型中的血管内皮功能有不同的调节作用。这表明不同的PE样变化存在不同的发病机制和途径。