[Effect of dopamine on intracerebral glutamate uptake ability in rats with minimal hepatic encephalopathy and the pathogenesis of minimal hepatic encephalopathy].

To investigate the effect of dopamine (DA) on the glutamate (Glu) uptake ability of neural cells, as well as its effect on cognitive impairment in rats with minimal hepatic encephalopathy (MHE) via related pathways. A total of 45 Sprague-Dawley rats were randomly divided into control group, MHE model group, and DA intervention model group, with 15 rats in each group. The rats in the MHE model group were given intraperitoneal injection of thioacetamide (TAA), those in DA intervention model group were given intraventricular injection of DA, and those in the control group were given intraperitoneal injection of physiological saline, with a frequency of twice a week for 8 weeks. Cerebral microdialysis was used to measure the change in the content of Glu in the brain in MHE rats and rats with DA intervention; RT-PCR and Western blotting were used to measure the relative mRNA and protein expression of trace amine-associated receptor 1 (TAAR1) and excitatory amino acid transporter 2 (EAAT2); the changes in the expression of EAAT2 and extracellular Glu level were measured after intracerebroventricular injection of TAAR1 siRNA and TAAR1 plasmid in MHE rats and rats with DA intervention. One- way analyses of variance for comparison among different groups were performed, categorical data between groups were compared using nonparametric tests. Compared with the control group, the MHE model group had significant increases in the content of DA in liver tissue, plasma, and brain tissue (4.90 ± 0.13 ng/g vs 1.20 ± 0.13 ng/g, < 0.05; 16.32 ± 1.01 pmol/ml vs 5.50 ± 0.82 pmol/ml, < 0.05; 732.45 ± 78.85 ng/g vs 387.00 ± 23.36 ng/g, < 0.05). There was a significant increase in the extracellular Glu level within 40-120 minutes after intracerebral injection of DA in the DA intervention model group. Compared with the control group, the MHE model group and the DA intervention model group had a significant increase in the relative protein expression of TAAR1 (3.72 ± 0.50/4.18 ± 0.43 vs 0.96 ± 0.40, both < 0.05) and a significant reduction in the expression of EAAT2 (0.46 ± 0.16/0.51 ± 0.20 vs 0.92 ± 0.11, = 0.013 and 0.036). Compared with the model group treated with empty vector, the MHE model group and the DA intervention model group had a significant increase in the relative protein expression of EAAT2 after TAAR1 siRNA intervention (0.86±0.142 vs 0.56 ± 0.060, = 0.028; 0.99 ± 0.056 vs 0.43 ± 0.098, = 0.0010) and a significant reduction in the extracellular Glu level in the brain at 60-120 minutes after injection, while after TAAR1 plasmid intervention, the MHE model group and the DA intervention model group had a significant reduction in the relative protein expression of EAAT2 (0.20 ± 0.040 vs 0.48 ± 0.08, = 0.006; 0.24 ± 0.05 vs 0.54 ± 0.07, = 0.004) and a significant increase in the extracellular Glu level in brain at 60-100 minutes after injection. DA interacts with TAAR1 in brain tissue to induce extracellular accumulation of Glu, thus leading to the disorder of the TAAR1-EAAT2 signaling pathway in brain tissue and ultimately injuring the cognitive function of MHE rats.