Huai J, Yang Z, Yi Y H, Wang G J, Xiang Q Q
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
Zhonghua Fu Chan Ke Za Zhi. 2018 Mar 25;53(3):183-189. doi: 10.3760/cma.j.issn.0529-567X.2018.03.008.
To investigate the modulation of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) expression by pravastatin in pre-eclampsia-like mouse model. C57BL/6J mice were randomly injected with N-nitro-L-arginine methyl ester (L-NAME) as pre-eclampsia-like model group (PE) or saline as normal pregnancy control group (Con) respectively, from gestational the 7th to 18th day. For each group, pravastatin (PE+Pra, Con+Pra group) or saline (PE+N, Con+N Group) was given from the 8th to 18th day of gestation, respectively. Liver and placenta of pregnant mice were collected on gestational day 18. The LCHAD protein expression and mRNA levels of liver and placenta were detected through western blot, immunohistochemistry and real-time quantitative PCR. (1) The average arterial pressure of pregnant mice increased gradually from the 8th to 18th day in PE+N group, but decreased in PE+Pra group from gestational 10th day, 24 hour urinary protein levels in PE+N group [(1 494 ± 201) μg] were significantly higher than that in Con+N group [(935±128) μg, <0.01], and also higher than that in PE+Pra group [(981±116) μg, 0.01].(2) The results of western blot: the expression of LCHAD was significantly lower in PE+N group (liver: 0.64±0.11, placenta: 0.48±0.06) than that in Con+N group (liver: 1.06±0.10, placenta: 0.60±0.10), and lower than that in PE+Pra group (liver: 0.99±0.04, placenta: 0.60±0.08; all <0.01).(3)The results of real-time quantitative PCR: the levels of LCHAD mRNA in liver and placenta in PE+N group (liver: 0.621±0.128, placenta: 0.646±0.129) were significantly decreased compared with Con+N group (liver: 1.007±0.130, placenta: 1.004±0.103; all <0.01), but there was no significant difference between PE+Pra group (liver: 0.693±0.678, placenta: 0.662±0.183; >0.05). (4) LCHAD protein was expressed widely and evenly in liver. The expression in placental cytotrophoblast and syncytial trophoblast cells located in outer layer of villous in labyrinth layer was the most. The expression of LCHAD was significantly lower in PE+N group (liver: 0.062±0.016, placenta: 0.147±0.018) than that in Con+N group (liver: 0.126±0.013, placenta: 0.183±0.024), and lower than that in PE+Pra group (liver: 0.111±0.017, placenta: 0.174±0.027; all <0.05). Pravastatin could upregulate the LCHAD protein expression of liver and placenta in the pre-eclampsia-like mouse, which may be a mechanism to improve the clinical manifestations of pre-eclampsia.
探讨普伐他汀对先兆子痫样小鼠模型中长链3-羟酰基辅酶A脱氢酶（LCHAD）表达的调节作用。将C57BL/6J小鼠从妊娠第7天至18天分别随机注射N-硝基-L-精氨酸甲酯（L-NAME）作为先兆子痫样模型组（PE）或注射生理盐水作为正常妊娠对照组（Con）。每组在妊娠第8天至18天分别给予普伐他汀（PE+Pra、Con+Pra组）或生理盐水（PE+N、Con+N组）。在妊娠第18天收集孕鼠的肝脏和胎盘。通过蛋白质免疫印迹法、免疫组织化学和实时定量PCR检测肝脏和胎盘的LCHAD蛋白表达及mRNA水平。（1）PE+N组孕鼠平均动脉压从第8天至18天逐渐升高，而PE+Pra组从妊娠第10天开始下降；PE+N组24小时尿蛋白水平[（1494±201）μg]显著高于Con+N组[（935±128）μg，<0.01]，也高于PE+Pra组[（981±116）μg，0.01]。（2）蛋白质免疫印迹法结果：PE+N组LCHAD表达（肝脏：0.64±0.11，胎盘：0.48±0.06）显著低于Con+N组（肝脏：1.06±0.10，胎盘：0.60±0.10），且低于PE+Pra组（肝脏：0.99±0.04，胎盘：0.60±0.08；均<0.01）。（3）实时定量PCR结果：PE+N组肝脏和胎盘LCHAD mRNA水平（肝脏：0.621±0.128，胎盘：0.646±0.129）与Con+N组（肝脏：1.007±0.130，胎盘：1.004±0.103；均<0.01）相比显著降低，但PE+Pra组（肝脏：0.693±0.678，胎盘：0.662±0.183；>0.05）之间无显著差异。（4）LCHAD蛋白在肝脏中广泛且均匀表达。在胎盘细胞滋养层和位于迷路层绒毛外层的合体滋养层细胞中表达最多。PE+N组LCHAD表达（肝脏：0.062±0.016，胎盘：0.147±0.018）显著低于Con+N组（肝脏：0.126±0.013，胎盘：0.183±0.024），且低于PE+Pra组（肝脏：0.111±0.017，胎盘：0.174±0.027；均<0.05）。普伐他汀可上调先兆子痫样小鼠肝脏和胎盘的LCHAD蛋白表达，这可能是改善先兆子痫临床表现的一种机制。
