Nrf2-ARE通路在子痫前期胎盘氧化应激中的作用

Roles of Nuclear Factor-E2 Related Factor 2-antioxidant Reponse Element Pathway in Oxidative Stress of Placentas in Preeclampsia

目的观察转录因子NF-E2相关因子2(Nrf2)-抗氧化反应序列元件(ARE)通路在子痫前期产妇胎盘组织表达,探讨Nrf2在子痫前期疾病中的作用。方法随机选择60例择期行子宫下段剖宫产术的子痫前期产妇,ASAⅠ-Ⅱ级,根据病情分为轻度子痫前期组(P1组,n=30)及重度子痫前期组(P2组,n=30),另外随机选择正常行剖宫产患者为空白对照组(C组,n=30)。胎儿取出后断脐前取脐静脉血检测瘤坏死因子-α(TNF-α)、丙二醛(MDA)、超氧化物歧化酶(SOD)活性;断脐后取胎盘组织用Western blot法检测Nrf2表达,免疫组化法检测血红素加氧酶-1(HO-1)的表达。结果与C组比较,P1、P2组患者脐静脉血TNF-α、MDA活性显著升高,SOD活性显著降低(P<0.05);与C组比较,P1、P2组患者胎盘组织的Nrf2与HO-1表达显著降低(P<0.05);与P1组比较,P2组患者TNF-α、MDA活性显著升高,SOD活性显著降低(P<0.05);与P1组比较,P2组患者胎盘组织的Nrf2与HO-1表达显著降低(P<0.05)。结论子痫前期患者胎盘组织抗氧化能力显著降低,其机制可能与核因子E2相关因子2表达下调有关。

Objective To evaluate the expression of Nrf2-ARE signaling pathway and its roles in oxidative stress of placentas in preeclampsia.Methods Sixty ASA Ⅰ or Ⅱ preeclamptic pregnancies were divided into mild preeclampsia group（ Grouop P1,n = 30） and severe preeclampsia （Grouop P2, n = 30）, based their blood pressure and urine protein preoperative. The control group was composed of 30 normal select caesarean section pregnants （Grouop C,n= 30）.The level of TNF-α, MDA and SOD activity of umbilical cord blood were detected of each group after delivery but before clipping the umbilical cord. Placental samples were obtained and the Nrf2 protein expression were dected by Western blot and the HO-1 protein expression were measured by immunohistochemical staining. Results There were no significant differences in each groups with respect to general information.Compared with the group C, the level of TNF-α, MDA of umbilical cord blood in group P1 and group P2 were increased significantly （P〈0.05）, but the SOD activity was decreased significantly （P〈0.05）.Compared with the group C, the Nrf2 protein expression and the HO-1 protein expression of group P1 and group P2 were decreased significantly （P〈0.05）.Compared with the group P1, the level of TNF-α, MDA of umbilical cord blood were increased significantly （P〈0.05）, but the Nrf2 protein expression and the HQ-1 protein expression were decreased significantly （P〈0.05）.Conclusion The ability of antioxidative stress of placentas in preeclampsia was decreased and the Nrf2-ARE pathway was involed in the development of preeclampsia.