Protective effect and mechanism of lipoxinA4 on oxidative injury in trophoblastic cells
10.3760/cma.j.issn.1007-9408.2011.07.004
- VernacularTitle:脂氧素对滋养细胞氧化损伤的保护作用及其机制
- Author:
Jianming GONG
;
Yinping HUANG
;
Biao TANG
;
Jinxia CHEN
;
Jie ZHOU
;
Yanjun HUANG
- Publication Type:Journal Article
- Keywords:
Trophoblasts;
Lipoxins;
Antioxidants;
NF-E2-related factor 2;
Reactive oxygen species;
Superoxide dismutase
- From:
Chinese Journal of Perinatal Medicine
2011;14(7):403-408
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore lipoxinA4 (LXA4) expression in maternal serum of pregnant women and the protective effect and mechanism of LXA4 on trophoblastic cells from oxidative injury. Methods Trophoblastic cells were randomized into six groups: Control group; Lipopolysaccharides (LPS) group, cells were stimulated by 10 μg/ml LPS for 24 h; Intervention group, cells stimulated by LPS were treated with 100 nmol/L LXA4 for 24 h; LXA4 group, cells were treated with 100 nmol/L LXA4 for 24 h; Antagonistic group, cells stimulated by LPS were treated with 100 nmol/L LXA4 plus 100 μmol/L N-tert-butoxycarbonyl-2-pyrrolidine (BOC-2) for 24 h; BOC-2 group, trophoblastic cells stimulated by LPS were treated with 100 μmol/L BOC-2 for 24 h. The serum concentration of LXA4 in normal group and preeclampsia group was detected by ELISA. The intracellular formation of reactive oxygen species (ROS) was detected by 2,7-dichlorofluorescein diacetate (DCFH-DA) as a fluorescent probe. SOD mRNA was analyzed by RT-PCR. SOD and Nrf2 protein expressions were analyzed by Western blot. The levels of SOD in trophoblastic cells were detected by using detection kit. Results (1) The serum concentration of LXA4 was significantly lower in preeclampsia group (165.53±18.89) pg/L than in the control [(545.67±30.91) pg/L, P<0.01]. (2) Compared with control group, the levels of ROS in LPS group were significantly higher, DCF density of trophoblastic cells increased from 53.00±3.08 to 77.00±5.83 (P<0.01). The expression of nuclear Nrf2 protein, SOD mRNA and protein in LPS group were obviously decreased (P<0.01). The levels of SOD in LPS group were also significantly lower (P<0.01). (3) Compared with LPS group, the levels of ROS in intervention group were significantly lower, DCF density of trophoblastic cells decreased from 77.00±5.83 to 62.00±3.39 (P<0.01). The expression of nuclear Nrf2 protein, SOD mRNA in intervention group were obviously increased (P<0.01), so did the SOD protein expression (P<0.05). The levels of SOD were significantly increased from (4.77±0.34) U/ml to (8.93±0.53) U/ml (P<0.01). (4) The levels of SOD in antagonistic group were lower than in intervention group, but still higher than LPS group. [(6.23±0.41) U/ml vs (8.93±0.53) U/ml (P<0.01) or (4.77±0.34) U/ml (P<0.01)]. No significant difference was found in the levels of SOD between BOC-2 and LPS group (P>0.05). Conclusions LXA4 can significantly reduce the oxidative stress of placental trophoblastic cells stimulated by LPS. LXA4 can bind to lipoxin receptors and activate Nrf2-ARE signaling pathway playing a protective effect. So LXA4 in pregnant women can affect the oxidative stress of placenta.
