Hyperammonemia enhances the function and expression of P‐glycoprotein and Mrp2 at the blood–brain barrier through NF‐κB

摘要: Ammonia is considered to be the main neurotoxin responsible for hepatic encephalopathy resulting from liver failure. Liver failure has been reported alter expression and activity of P-glycoprotein (P-gp) multidrug resistance-associated protein 2 (Mrp2) at blood-brain barrier (BBB). The aim this study was investigate whether ammonia involved in abnormalities P-gp Mrp2 BBB. Hyperammonemic rats were developed by an intraperitoneal injection ammonium acetate (NH4 Ac, 4.5 mmol/kg). Results showed that function markedly increased cortex hippocampus 6 h following NH4 Ac administration. Significant increase observed rats. Meanwhile, such alterations line with mRNA levels Mrp2. nuclear amount factor-κB (NF-κB) p65 also observed. Primarily cultured rat brain microvessel endothelial cells (rBMECs) used vitro study. Data indicated 24 exposure significantly rBMECs, accompanied activation NF-κB. Furthermore, induced reversed NF-κB inhibitor. In conclusion, demonstrates hyperammonemia increases BBB via activating pathway. Hyperammonemia, a proverbial factor neurocognitive disorder (BBB) dysfunction failure, could both vivo vitro. stimulated may potential mechanism underlying hyperammonemia.