Protective effects and its mechanism on neural cells after folic acid intervention in preeclampsia rat model

Abstract

To investigate protective effects and mechanism of folic acid on brain neural cells in preeclampsia rat model. Adult pregnant Wistar rats were randomly divided into 4 groups (n = 10 in each group). Rats in model group were injected intraperitoneally with homocysteine (Hcy, 200 mg × kg(-1) × d(-1)) daily and were injected subcutaneously every other day with monosodium glutamate (MSG, 1 g × kg(-1)· 48 h(-1)) from the 10th day of pregnancy to establish the model of preeclampsia. Low-dose folic acid (low dose group 10 mg × kg(-1) × d(-1)) and high-dose folic acid (high dose group 20 mg × kg(-1) × d(-1)) were given intragastric administration with folic acid tablets dissolved in saline daily at the same time of establishing model. Rats in control group were injected or intragastric administration with the same dose of saline as above up to the 20th day of pregnancy. Brain tissue was fixed on the 20th day of pregnancy, so was that plasma folic acid was measured with automatic electro-chemiluminescence. Rats' neural nerve cells apoptosis was observed with tunel. Nuclear factor (NF)-κB activation was observed with immunohistochemical staining. bcl-2 mRNA and protein expression changes were observed by using reverse transcription (RT)-PCR and western blot. (1) Plasma folate concentrations were (39.5 ± 3.4) nmol/L in low dose group and (40.1 ± 5.4) nmol/L in high dose group, which were all significantly higher than (26.9 ± 6.7) nmol/L in model group (P < 0.01). Plasma folate in low dose and high dose group did not show significant difference (P > 0.05); (2) Apoptosis cell were 48.2 ± 9.1 in low dose group and 44.7 ± 8.3 in high dose group, which were significantly lower than 75.8 ± 10.1 in model group (P < 0.01). However, apoptosis cell in low dose and high dose group did not show significant difference (P > 0.05); (3) NF-κB activation were 48 ± 9 in low dose group and 45 ± 8 in high dose group, which were significantly lower 76 ± 10 in model group (P < 0.01). NF-κB activation in low dose and high dose group did not show significant difference (P > 0.05); (4) bcl-2 mRNA and protein expression were 0.98 ± 0.49 and 0.89 ± 0.52 in low dose group and 0.95 ± 0.38 and 0.92 ± 0.47 in high dose group which was significantly higher than 0.62 ± 0.20 and 0.45 ± 0.37 in model group (P < 0.01); bcl-2 expression in low dose and high dose group showed no significant difference (P > 0.05). Folic acid has a protective role on neural cells in preeclampsia model rats. The anti-apoptosis mechanism may be related with inhibiting NF-κB activation and promoting bcl-2 gene and protein expression.