Effects of baicalin on mitochondria apoptotic pathway of trophoblast cells in a preeclampsia rat model

Objective To explore the effects of baicalin in the treatment of a preeclampsia (PE) rat model by detecting the expression of X-linked inhibitor of apoptosis protein (XIAP) and cysteine containing aspartate-9 (Caspase-9) and observing the ultrastructure of mitochondria in trophoblast cells. Methods Forty-eight pregnant Wistar rats were randomly divided into two groups: 12 in the control group and 36 in the PE model group. The PE model was established with subcutaneous injection of l-nitro arginine methyl ester with 100 mg/kg per day from the 13th day of pregnancy. Beginning from the 16th day of pregnancy, the PE rats were injected with different doses of baicalin till cesarean section, and divided into three groups: non-intervention PE model group treated with saline (NIP group), low-dose baicalin intervention group (IDB group) at 50 mg/kg per day, and high-dose baicalin intervention group (HDB group) at 100 mg/kg per day. The rat tail artery blood pressure and 24-h urine protein level were measured at pregnant day 10, 16 and 20. The levels of XIAP and Caspase-9 in placenta were measured by immunohistochemistry. The ultrastructure of mitochondria of trophoblast cells of the rat placenta was observed under electron microscope. T test, F test and LSD-t test were applied for statistical analysis. Results (1) On pregnant day 10, no significant differences were observed in rat tail artery systolic blood pressure, diastolic blood pressure and 24-h urine protein level between the control group and PE model group (all P>0.05). On pregnant day 16 and 20, the systolic blood pressure, diastolic blood pressure and 24-h urine protein level of NIP, IDB and HDB groups were significantly higher than those of control group [pregnant day 16: systolic blood pressure: (137.74±5.21),(136.15±4.86),(138.28±4.79) and (110.57±3.79) mmHg (1 mmHg=0.133 kPa), diastolic blood pressure:(89.58±5.50), (88.45±8.59), (89.42±6.29) and (80.28±7.36) mmHg, 24-h urine protein: (7.78±0.45), (7.53±0.54), (7.86±0.57) and (6.45±0.56) mg; pregnant day 20: systolic blood pressure: (145.26±4.67), (131.28±4.34), (130.93±5.33) and (110.40±6.92) mmHg, diastolic blood pressure: (89.87±6.55), (85.34±7.33), (84.64±7.36) and (80.19±7.34) mmHg, 24-h urine protein: (11.18±0.42), (9.65±0.54), (9.06±0.56) and (6.31±0.45) mg] (all P 0.05). (2)Compared with NIP group, the expression of XIAP in control group, IDB and HDB groups were significantly increased(210.39±0.78,180.56±0.82,195.36±0.96 and 192.84±1.06, all P<0.01). There was no significant difference in the expression of XIAP between IDB and HDB groups (P=0.66). The expression of Caspase-9 in control group, IDB and HDB groups were significantly decreased compared with NIP group (210.36±0.55, 195.53±0.96, 198.42±1.01 and 185.25±0.64, all P<0.01). There was no significant difference in the expression of Caspase-9 between IDB and HDB groups (P=0.65). Ultrastructure of mitochondria in NIP group showed different degrees of damage, matrix swelling, and mitochondrial cristae bresk or disappearance. In IDB group, mitochondrial matrix swelling was not obvious, and mitochondrial cristae were visible. In HDB group, mitochondrial cristae were neat and clear. Conclusions Baicalin may play an important role in the treatment of preeclampsia by reversing the trophoblast apoptosis and improving the ultrastructure of mitochondria through its regulation of XIAP expression and downregulation of Caspase-9 expression. Key words: Pre-eclampsia; Baicalin; Trophoblasts; X-Linked inhibitor of apoptosis protein; Caspase-9; Apoptosis; Rats