Expression of gamma-aminobutyric acid A receptor subunits α1 β1 γ2 mRNA in rats with hepatic encephalopathy

摘要

AIM: To investigate the mRNA expression of gamma-aminobutyric acid A (GABAA) receptor subunits α1, β1, γ2 in different parts of the brain of rats with hepatic encephalopathy.METHODS: Twelve adult male Sprague-Dawley rats were randomly divided into two groups: (1) hepatic encephalopathy model group (n = 6), which was induced by intraperitoneal injection of thioacetamide (TAA, 350 mg/kg) for three consecutive days; (2) control group (n = 6), in which the rats were treated with same dose of normal saline solution. After the freeze slice of cerebrum was made, in situ hybridization was used to detect the mRNA of GABAA receptor subunits α1, β1, and γ2 in rat cerebral cortex, basal nuclei, substantia nigra and hippocampi. Image data were collected and analyzed quantitatively by QWin550CW model image signal gather and analysis system.RESULTS: In rats with hepatic encephalopathy, mRNA expression levels of GABAA receptor subunits α1, β1 increased significantly in basal nuclei, substantia nigra pars compacta, substantia nigra pars reticularis and hippocampi (144.7±15.67/184.14±4.41, 60.61±33.66/113.07±32.44, 87.71± 21.25/128.40±18.85, 122.34±5.56/161.60±4.56, 123.29±5.21/140.65±4.15, 123.40±4.42/140.09±4.52, 124.76±4.18/140.09±4.12, 141.62±15.09/182.80 ±5.20, 69.13±30.74/134.21±43.76, 87.87±25.16/151.01±19.49, 122.14±6.30 /162.33±3.92, 122.81±5.09/137.19±7.12, 123.00±4.63/138.11±5.92, 125.75 ±2.43/138.81±6.10, P<0.01), but did not change in the cerebral cortex compared to the control group. Similar changes were found in the mRNA expression levels of GABAA receptor subunit γ2, which increased significantly in basal nuclei, substantia nigra pars compacta, substantia nigra pars reticularis (136.81±26.41/167.97±16.23, 51.00±36.14/113.18±36.52, 86.35±20.30/ 126.90±19.74, P<0.01), CA1 of hippocampal (162.15±9.05/178.62±6.45, P<0.05), and no changes were found in the cerebral cortex and CA2, CA3, CA4 of hippocampi.CONCLUSION: In rats with hepatic encephalopathy, mRNA expression levels of GABAA receptor subunits α1, β1, γ₂ increase significantly in basal nuclei, substantia nigra and hippocampi, suggesting that the changes of mRNA expression levels in GABA_A receptor subunits may contribute to the pathogenesis of hepatic encephalopathy.