高效抗氧化剂线粒体辅酶Q对子痫前期大鼠血压及胎盘线粒体功能障碍的作用研究

Effect of antioxidant MitoQ on blood pressure and placental mitochondrial dysfunction in the rat model of preeclampsia

摘要:

目的 研究高效抗氧化剂线粒体辅酶Q（MitoQ）对子痫前期大鼠血压及胎盘线粒体功能障碍的作用，并探讨相关机制。方法 选取30只子痫前期大鼠，随机分为子痫前期组、MitoQ组、MitoQ+鸦胆苦醇（Brusatol）组，每组10只；另取10只SD大鼠作为对照组。妊娠第14天MitoQ组腹腔注射MitoQ 3.5 mg/kg；MitoQ＋Brusatol组腹腔注射MitoQ 3.5 mg/kg，灌胃Brusatol 1 mg/kg；对照组、子痫前期组腹腔注射、灌胃等体积生理盐水，1次/d，干预至妊娠第19天。检测妊娠第15天、17天、19天收缩压；紫外比色法检测线粒体膜通透性改变孔（PT）活性；Western blotting检测胎盘组织核因子E2相关因子2（Nrf2）、抗氧化反应元件（ARE）蛋白的表达。结果 各组大鼠妊娠第15天、17天、19天收缩压比较，采用重复测量设计的方差分析，结果 ①不同时间点收缩压无差异（F =0.045，P =0.963）；②各组收缩压有差异（F =15.111，P =0.000）；③各组收缩压变化趋势有差异（F =16.889，P =0.000）。子痫前期组PT活性高于对照组和MitoQ组（P <0.05）；MitoQ+Brusatol组高于MitoQ组（P <0.05）。子痫前期组Nrf2、ARE蛋白相对表达量低于对照组和MitoQ组（P <0.05）；MitoQ+Brusatol组低于MitoQ组（P <0.05）。结论 高效抗氧化剂MitoQ可降低子痫前期大鼠血压，改善胎盘线粒体功能及结构，其治疗作用可能通过调控Nrf2/ARE通路来实现。

Abstract:

Objective To study the effects of antioxidant mitoquinone (MitoQ) on blood pressure and placental mitochondrial dysfunction in the rat model of preeclampsia, and to explore the underlying mechanisms.Methods A total of 30 rats with preeclampsia were randomly divided into preeclampsia group, MitoQ group, and MitoQ + brusatol group, with 10 rats in each group. In addition, another 10 SD rats were selected as the control group. On the 14th day of gestation, rats in the MitoQ group were intraperitoneally injected with MitoQ at a dose of 3.5 mg/kg. The rats in the MitoQ + brusatol group were intraperitoneally injected with MitoQ at a dose of 3.5 mg/kg, and administered intragastrically with brusatol at a dose of 1 mg/kg. The rats in the control group and preeclampsia group were injected intraperitoneally and intragastrically with the same amount of normal saline once a day until the 19th day of gestation. The systolic blood pressure on the 15th, 17th, and 19th days of gestation was measured. The mitochondrial permeability transition pore (PT) activity was determined via colorimetry. The expression of nuclear factor E2-related factor 2 (Nrf2) and antioxidant response element (ARE) in placenta tissues were detected by Western blotting.Results There was no difference in systolic blood pressure at different time points (F = 0.045, P = 0.963). The systolic blood pressure (F = 15.111, P = 0.000) and the changing trend thereof (F = 16.889, P = 0.000) were different among the groups. The PT activity in the preeclampsia group was higher than that in the control group and MitoQ group (P < 0.05). Compared with the MitoQ group, the PT activity in the MitoQ + Brusatol group was also higher (P < 0.05). The placental expression of Nrf2 and ARE proteins in the preeclampsia group was lower than that in the control group and MitoQ group (P < 0.05). In addition, the placental expression of Nrf2 and ARE proteins was lower in the MitoQ + Brusatol group relative to the MitoQ group (P < 0.05).Conclusions The antioxidant MitoQ can lower the blood pressure of rats with preeclampsia and improve the placental mitochondrial function and structure. Its therapeutic effects may be achieved by regulating the Nrf2/ARE pathway.