To investigate the effects of luteolin (LUT) on trophoblast cells in preeclampsia rats and the mechanisms.

Ten day gestational SD rats were randomly divided into normal control (NC) , model (M) and LUT groups with different concentrations (20, 40 and 60 μmol/L) (LUT-L, LUT-M, LUT-H) , and there were 12 rats in each group. The rats in the model and the administration groups were subcutaneously injected with 100 mg/ (kg·d) nitrosyl L-arginine methyl ester once a day for 6 days. And the rats in the control group were subcutaneously injected with the same amount of normal saline. Then, 16-day gestational rats in LUT-L, LUT-M and LUT-H groups were intraperitoneally injected with LUT 20, 40 and 60 μmol/L respectively, and the 16-day gestational rats of in NC group and M group were intraperitoneally injected with the same amount of normal saline, once a day for 5 days. The tail artery blood pressure and 24 h urine protein were measured on the 10th, 16th and 21st day of pregnancy; on the 21st day of gestation, apoptosis of trophoblast was detected by TUNEL, and the expressions of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) , phosphatidylinositol-3 kinase (PI3K) , phospho-PI3K (p-PI3K) , protein kinase B (Akt) , phospho-AKT (p-Akt) , endothelial nitric oxide synthase (eNOS) and phospho-eNOS (p-eNOS) proteins in trophoblast were detected by Western blot. One-way ANOVA was used for comparison between groups, SNK-q test was used for further comparison between the two groups.

On the 10th day of gestation, there was no significant difference in systolic blood pressure and diastolic blood pressure of tail artery and 24-hour urinary protein content between each group (P > 0.05) ; on the 16th day of gestation, compared with NC group, the systolic blood pressure and diastolic blood pressure of tail artery and 24-hour urinary protein content were significantly increased in M, LUT-L, LUT-M and LUT-H groups (P < 0.05) ; on the 21st day of gestation, compared with NC group, the systolic blood pressure (110.33±3.67 vs 147.28±4.16, 131.29±4.31, 124.46±4.27, 118.54±4.18) 24-hour urinary protein content, the apoptosis rates (1.38±0.34 vs 43.45±3.72, 39.21±3.53, 27.86±3.41, 23.21±3.28) , and the protein expression of Bax were significantly increased (all P < 0.05) ; and protein expression of Bcl2, p-PI3K/PI3K (1.06±0.09 vs 0.25±0.02, 0.37±0.03, 0.57±0.06, 0.73±0.08) , p-Akt/Akt (0.87±0.08 vs 0.11±0.01, 0.23±0.03, 0.56±0.07, 0.78±0.06) , p-eNOS/eNOS (0.85±0.07 vs 0.09±0.01, 0.16±0.02, 0.38±0.04, 0.69±0.07) were significantly decreased (P < 0.05) ; compared with M group, the systolic blood pressure, diastolic blood pressure of tail artery, 24-h urinary protein apoptotic rate of trophoblast and Bax protein expression were significantly decreased in LUT-L, LUT-M, and LUT-H groups (P < 0.05) , where as the expressions of Bcl-2, p-PI3K/PI3K, p-Akt/Akt, p-eNOS/eNOS proteins were significantly increased (all P < 0.05) .

LUT can inhibit the apoptosis of trophoblast in PE rats, and PI3K/Akt/eNOS signaling pathway maybe involve in regulating these apoptotic related proteins.