Yi Yan-Hong, Yang Zi, Han Yi-Wei, Huai Jing
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
Chin Med J (Engl). 2017 May 5;130(9):1033-1041. doi: 10.4103/0366-6999.204924.
The pathogenesis of some types of preeclampsia is related to fatty acid oxidation disorders. Rapamycin can regulate fatty acid metabolism. This study aimed to investigate the effects of rapamycin on the clinical manifestations and blood lipid parameters in different preeclampsia-like mouse models.
Two preeclampsia-like mouse models and a control group were established: L-NA (injected with Nω-nitro-L-arginine methyl ester), LPS (injected with lipopolysaccharide), and the control group with normal saline (NS). The mouse models were established at preimplantation (PI), early- and late-pregnancy (EP, LP) according to the time of pregnancy. The administration of rapamycin (RA; L-NA+RA, LPS+RA, and NS+RA) or vehicle as controls (C; L-NA+C, LPS+C, NS+C) were followed on the 2nd day after the mouse models' establishment. Each subgroup consisted of eight pregnant mice. The mean arterial pressure (MAP), 24-h urinary protein, blood lipid, fetus, and placental weight were measured. The histopathological changes and lipid deposition of the liver and placenta were observed. Student's t-test was used for comparing two groups. Repeated measures analysis of variance was used for blood pressure analysis. Qualitative data were compared by Chi-square test.
The MAP and 24-h urinary protein in the PI, EP, and LP subgroups of the L-NA+C and LPS+C groups were significantly higher compared with the respective variables in the NS+C group (P < 0.05). The preeclampsia-like mouse models were established successfully. There was no significant difference in the MAP between the PI, EP, and LP subgroups of the L-NA+RA and L-NA+C groups and the LPS+RA and LPS+C groups. The 24-h urine protein levels in the PI and EP subgroups of the L-NA+RA group were significantly lower compared with the respective levels in the L-NA+C groups (1037 ± 63 vs. 2127 ± 593 μg; 976 ± 42 vs. 1238 ± 72 μg; bothP < 0.05), also this effect appeared similar in the PI and EP subgroups of the LPS+RA and LPS+C groups (1022 ± 246 vs. 2141 ± 432 μg; 951 ± 41 vs. 1308 ± 30 μg; bothP < 0.05). The levels of serum-free fatty acid (FFA) in the PI and EP subgroups of the L-NA+RA groups were significantly lower compared with the respective levels in the L-NA+C group (2.49 ± 0.44 vs. 3.30 ± 0.18 mEq/L; 2.23 ± 0.29 vs. 2.84 ± 0.14 mEq/L; bothP < 0.05). The levels of triglycerides (TG) and total cholesterol in the PI subgroup of the L-NA+RA group were significantly lower compared with the respective levels in the L-NA+C (1.51 ± 0.16 vs. 2.41 ± 0.37 mmol/L; 2.11 ± 0.17 vs. 2.47 ± 0.26 mmol/L; bothP < 0.05), whereas high-density lipoprotein serum concentration was significantly higher (1.22 ± 0.19 vs. 0.87 ± 0.15 mmol/L;P < 0.05) and low-density lipoprotein serum concentration did not exhibit a significant difference. There were no significant differences in the FFA of the PI, EP, and LP subgroups between the LPS+RA and the LPS+C groups. The levels of TG in the PI subgroup of the LPS+RA group were significantly lower compared with the respective levels in the LPS+C group (0.97 ± 0.05 vs. 1.22 ± 0.08 mmol/L;P < 0.05).
Rapamycin can improve clinical manifestations and blood lipid profile in part of the preeclampsia-like mouse models.
某些类型子痫前期的发病机制与脂肪酸氧化紊乱有关。雷帕霉素可调节脂肪酸代谢。本研究旨在探讨雷帕霉素对不同子痫前期样小鼠模型临床表现及血脂参数的影响。
建立两种子痫前期样小鼠模型及一个对照组：L-NA组（注射Nω-硝基-L-精氨酸甲酯）、LPS组（注射脂多糖），对照组注射生理盐水（NS）。根据妊娠时间在植入前（PI）、妊娠早期和晚期（EP、LP）建立小鼠模型。在小鼠模型建立后第2天给予雷帕霉素（RA；L-NA+RA、LPS+RA、NS+RA）或作为对照的赋形剂（C；L-NA+C、LPS+C、NS+C）。每个亚组由8只妊娠小鼠组成。测量平均动脉压（MAP）、24小时尿蛋白、血脂、胎儿及胎盘重量。观察肝脏和胎盘的组织病理学变化及脂质沉积。两组比较采用Student's t检验。血压分析采用重复测量方差分析。定性数据采用卡方检验比较。
L-NA+C组和LPS+C组PI、EP和LP亚组的MAP和24小时尿蛋白显著高于NS+C组相应变量（P<0.05）。成功建立了子痫前期样小鼠模型。L-NA+RA组和L-NA+C组、LPS+RA组和LPS+C组的PI、EP和LP亚组之间的MAP无显著差异。L-NA+RA组PI和EP亚组的24小时尿蛋白水平显著低于L-NA+C组相应水平（1037±63 vs. 2127±593μg；976±42 vs. 1238±72μg；均P<0.05），LPS+RA组和LPS+C组的PI和EP亚组也出现类似效果（1022±246 vs. 2141±432μg；951±41 vs. 1308±30μg；均P<0.05）。L-NA+RA组PI和EP亚组的血清游离脂肪酸（FFA）水平显著低于L-NA+C组相应水平（2.49±0.44 vs. 3.30±0.18mEq/L；2.23±0.29 vs. 2.84±0.14mEq/L；均P<0.05）。L-NA+RA组PI亚组的甘油三酯（TG）和总胆固醇水平显著低于L-NA+C组相应水平（1.51±0.16 vs. 2.41±0.37mmol/L；2.11±0.17 vs. 2.47±0.26mmol/L；均P<0.05），而高密度脂蛋白血清浓度显著更高（1.22±0.19 vs. 0.87±0.15mmol/L；P<0.05），低密度脂蛋白血清浓度无显著差异。LPS+RA组和LPS+C组PI、EP和LP亚组的FFA无显著差异。LPS+RA组PI亚组的TG水平显著低于LPS+C组相应水平（0.97±0.05 vs. 1.22±0.08mmol/L；P<0.05）。
雷帕霉素可改善部分子痫前期样小鼠模型的临床表现和血脂谱。
