MEDLINE/PubMed Journal Browser Search

Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

Title: [Different effects of pravastatin on sFlt-1, PlGF and VEGF in different preeclampsia-like mouse models].
Author: Xiang QQ, Yang Z, Huai J, Wang GJ.
Journal: Zhonghua Fu Chan Ke Za Zhi; 2019 Sep 25; 54(9):601-607. PubMed ID: 31550776.
Abstract:
Objective: 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. Methods: 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). Results: (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 P<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 P<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 P<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 P<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 P>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 P>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 P>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 P>0.05). Conclusions: 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. 目的： 研究不同子痫前期（PE）样模型小鼠中普伐他汀（Pra）对可溶性血管内皮生长因子受体1（sFlt-1）、胎盘生长因子（PlGF）、血管内皮生长因子（VEGF）的不同作用。 方法： 采用C57BL/6J小鼠皮下注射亚硝基左旋精氨酸甲酯（L-NAME）或腹腔内注射脂多糖（LPS）建立2种PE样小鼠模型，同期注射生理盐水为正常对照；再分别于妊娠第8天始每天Pra灌胃（L-NAME+Pra组、LPS+Pra组、正常+Pra组）或生理盐水灌胃（L-NAME+生理盐水组、LPS+生理盐水组、正常+生理盐水组）。于妊娠第18天时收集6组孕鼠的肝脏、胎盘组织及血液，通过ELISA、蛋白印迹法、实时荧光定量PCR技术，比较sFlt-1、PlGF及VEGF在各组孕鼠肝脏、胎盘组织及血清中的表达情况。 结果： （1）ELISA的结果：L-NAME+Pra组孕鼠血清中VEGF[分别为205.70±3.43、154.60±2.31]、PlGF[分别为131.50±3.75、101.50±4.31]的水平较L-NAME+生理盐水组均明显上升（P均<0.05）；LPS+Pra组孕鼠血清中VEGF[分别为202.30±4.90、144.50±6.71]、PlGF[分别为121.50±3.86、95.41±4.08]的水平较LPS+生理盐水组均明显上升（P均<0.05）。LPS+Pra组孕鼠较LPS+生理盐水组、L-NAME+Pra组孕鼠较L-NAME+生理盐水组的血清sFlt-1[分别为3.01±0.50、776.60±80.06；2.60±0.06、583.70±9.83]，水平分别比较，均明显下降（P均<0.05）。（2）蛋白印迹法结果：L-NAME+Pra组孕鼠的肝脏组织PlGF[分别为1.34±0.12、0.66±0.14]、VEGF[分别为1.34±0.12、0.66±0.14]蛋白的表达水平均明显高于L-NAME+生理盐水组（P均<0.05）；L-NAME+Pra组孕鼠胎盘的PlGF和VEGF蛋白表达水平与L-NAME+生理盐水组比较，差异均无统计学意义（P均>0.05）；LPS+Pra组孕鼠的胎盘及肝脏组织的PlGF、VEGF蛋白的表达水平与LPS+生理盐水组比较，差异均无统计学意义（P均>0.05）。（3）实时荧光定量PCR技术结果：L-NAME+Pra组孕鼠胎盘及肝脏组织中的PlGF mRNA、VEGF mRNA的表达水平与L-NAME+生理盐水组比较，差异均无统计学意义（P均>0.05）；LPS+Pra组孕鼠胎盘及肝脏组织的PlGF mRNA及VEGF mRNA的表达水平分别与LPS+生理盐水组比较，差异均无统计学意义（P均>0.05）。 结论： Pra对不同PE模型样小鼠的血管内皮功能有不同的调节作用，不同的PE样变化存在不同的发病机制和通路。.

[Abstract] [Full Text] [Related] [New Search]