Different Effects of Pravastatin on Preeclampsia-like Symptoms in Different Mouse Models
Jing Huai, Zi Yang, Yan-Hong Yi, Guang-Jiao Wang
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China, china
Dr. Zi Yang
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191
Source of Support: None, Conflict of Interest: None
Background: Pravastatin (Pra) exerts protective effects on preeclampsia. Preeclampsia is a multifactorial and pathogenic pathway syndrome. The present study compared the effects of Pra on clinical manifestations of preeclampsia in different pathogenic pathways.
Methods: Two different preeclampsia-like mouse models used in this study were generated with Nω-nitro-L-arginine methyl ester (L-NAME) and used lipopolysaccharide (LPS) from day 7 of gestation, respectively. Pra treatment was administered on day 2 after the models were established in each group (L-NAME + Pra, LPS + Pra, and Control + Pra, n = 8) or normal saline (NS) for the control group (L-NAME + NS, LPS + NS, and Control + NS, n = 8). Maternal weight, serum lipids, the histopathological changes, and lipid deposition in the liver and placenta were observed. The pregnancy outcomes were compared. The blood pressure analysis was carried out on repeated measurements of variance. Student's t-test was used for comparing the two groups. The enumeration data were compared by Chi-square test.
Results: The mean arterial pressure (MAP) and 24-h urinary protein in the L-NAME + NS and LPS + NS groups were significantly higher than the Control + NS group (F = 211.05 and 309.92 for MAP, t = 6.63 and 8.63 for 24-h urinary protein; all P < 0.05) and reduced in the L-NAME + Pra group as compared to the L-NAME + NS group (F = 208.60 for MAP, t = 6.77 for urinary protein; both P < 0.05). Urinary protein was decreased in the LPS + Pra group as compared to the LPS + NS group (t = 5.33; P < 0.05), whereas MAP had no statistical significance (F = 3.37; P > 0.05). Compared to the Control + NS group, the placental efficiency in the L-NAME + NS and LPS + NS groups decreased significantly (t = 3.09 and 2.89, respectively; both P < 0.05); however, no significant difference was observed in L-NAME + Pra and LPS + Pra groups (t = 1.37 and 0.58, respectively; both P > 0.05). Free fatty acid was elevated in the L-NAME + NS group as compared to the Control + NS group (t = 3.99; P < 0.05) at day 18 of pregnancy and decreased in the L-NAME + Pra group as compared to the L-NAME + NS group (t = 3.28; P < 0.05); however, no significant change was observed in the LPS model (F = 0.32; P > 0.05).
Conclusion: This study suggested that Pra affected the clinical manifestations differently in preeclampsia-like mouse models generated in various pathogenic pathways.
目的: 普伐他汀 (pravastatin, Pra) 在子痫前期中具有保护作用, 但子痫前期是一种多因素, 多致病通路的综合征, 本研究旨在观察及比较普伐他汀对不同致病因素的子痫前期临床表现的影响。
方法: 自孕7天开始分别注射左硝基精氨酸甲酯 (Nw-nitro-L-arginine methyl ester, L-NAME) 及脂多糖 (lipopolysaccharide, LPS) 建立两种子痫前期样小鼠模型, 建模第2天用普伐他汀 (L-NAME + Pra, LPS + Pra, Control + Pra, n = 8) 进行灌胃, 生理盐水(L-NAME + NS, LPS + NS, Control + NS, n = 8) 作为对照。 观察及比较各组小鼠妊娠结局, 血脂水平, 肝脏和胎盘病理形态学改变及脂质沉积情况。 血压值用重复测量方差分析方法进行分析, 计量资料两组间比较用t检验, 计数资料用卡方检验进行分析。
结果: 平均动脉压及24小时尿蛋白水平在L-NAME + NS, LPS + NS组比 Control + NS 组显著升高 (血压值F = 211.05, 309.92, 尿蛋白水平 t = 6.63, 8.63；P < 0.05), 在L-NAME + Pra组与L-NAME + NS组相比降低（血压值F = 208.60, 蛋白尿t = 6.77; P < 0.05)。 LPS + Pra组与LPS + N组相比, 蛋白尿水平降低 (t = 5.33; P < 0.05), 而平均动脉压无显著差异 (F = 3.37, P > 0.05)。 与Control + NS组相比, 胎盘效率在L-NAME + NS组, LPS + NS组降低 (t = 3.09, 2.89; P < 0.05); 而在L-NAME + Pra组, LPS + Pra组无显著性差异(t = 1.37, 0.58; P > 0.05)。 孕18天游离脂肪酸水平在L-NAME + NS组显著高于Control + NS组 (t = 3.99; P < 0.05), 而在L-NAME + Pra组比L-NAME + N组显著降低 (t = 3.28; P < 0.05), 在LPS模型各组无显著性变化 (F = 0.32; P > 0.05)。