This study aimed at investigating the expression of nuclear factor kappa B (NF-κB) and mammalian target of rapamycin (mTOR) related signal pathways in liver tissues of intrahepatic cholestasis of pregnancy animal models.
Estrogen (EE)-induced cholestasis and a placental ischemia-reperfusion (IR) model were established in pregnant rats. All pregnant rats were divided into four groups: EE-IR group (n = 6), EE-sham group (n = 6), control-IR group (n = 6) and control-sham group (n = 6). Liver expression of mTOR, its upstream regulator DNA damage response-1 (REDD1), and downstream factor glucose transporter type-1 (GLUT1), accompanied by NF-κB (p65 is the most important component), its activator toll-like receptor 4 (TLR4), and inhibitor IκBα, were detected by western blot analysis and real-time polymerase chain reaction. The intergroup comparisons were performed with a 1-way analysis of variance, the comparisons among groups were analyzed with the nonparametric Kruskal-Wallis test.
Giving pregnant rats EE alone reduced the hepatic expression of IκBα (P = 0.008). Meanwhile, giving pregnant rats placental IR alone increased liver levels of REDD1 (P = 0.025), GLUT1 (P = 0.039), TLR4 (P = 0.010), and p65 (P = 0.023), and decreased hepatic mTOR (P = 0.001) and IκBα (P = 0.014) expression. Subjecting EE-treated rats to placental IR did not further alter liver levels of GLUT1 (P = 0.240), TLR4 (P = 0.129), or p65 (P = 0.145), whereas it did decrease hepatic mTOR (P = 0.008) and IκBα (P = 0.004) expression and enhance REDD1 expression (P = 0.009). Placental IR stress did impact the hepatic expression of REDD1-mTOR-GLUT1 and TLR4/NF-κB/IκBα in pregnant rats.
Placental IR-induced hepatic GLUT1, TLR4, and p65 alternation, which respond efficiently in control rats, were impaired in EE-induced ICP rats.