The Effect Of RuHuang Pill On The Express And Regulatory Of Rat GABA,Glu With Hepatic Encephalopathy Of Type A

Objective Hepatic encephalopathy (HE) of type A is a kind of hepatic encephalopathy associated with acute liver function failure. At present, a great quantity of research indicated that major inhibitory neurotransmitter GABA and the major excitatory neurotransmitter Glutamate had significancely effect on the process of HE. We researched the pathogenesis of HE to confirm neurotransmitter played an important role in HE and to reveal the impossible mechanisms and target of RuHuang Pill.Methods 1.96 Wistar male rats of SPF were randomly divided into six groups: normal control group (group A), model control group (group B), lactulose group (group C), RuHuang Pill group of small dose (group D), RuHuang Pill group of middle dose (group E), RuHuang Pill group of large dose (group F). After fasted overnight for over 14h, all rats except group A were induced to be the model of HE of type A by administration with thioacetamide (TAA 250mg ? kg-1 Oh,24h, ig). Before two hours of administration with TAA, each rats in group A and group B were given normal saline 10ml ? kg-1, and the left were given the same volume medicine respectively, then redone it every 8h. From the first administration with TAA to the end of experiment, every rat was injected mixture solution contained 10% glucose 3ml, saline 1ml, and 20umol/L KC1 ? L-1 every 8h to avoid hypoglycemia. At 30h of the experiment, electroencephalogram(EEG) was examined foreach group. During the experiment, observed the rats behavior. 2. Examined liver function ( serum ALT,AST,TBil ), serum TNF-α andendotoxin, ammonia concentration and GABA in the blood.3.Observed the ultrastructure of liver under electron microscopy. 4. Detected concentration of ammonia from spinal fluids. 5. Examined the content of glutamate and GABA by high performance liquid chromatography ( HPLC ) . 6. Observed the expression of receptor GABA in cerebral cortex. 7. Examined the expression of GLASTmRNA and PTBRmRNA in cerebral cortex by reverse transcription-coupled polyme rase chain reaction (RT-PCR).Result 1. In the group B, the rats' behavior were serious, the concentrations of blood ammonia and serum ALT,AST,TBil, TNF-α and endotoxin increased very high than group A(P<0. 01). While in the C, D,E,F, the rats'behavior were better, the concentrations of blood ammonia and serum ALT,AST,TBil,TNF-α and endotoxin were significantly lower than group B(P<0. 01). Group E was the best one. 2. The ultrastructures of liver were ameliorated in the group C,D, E,F and group E is better than group C,D,F. 3. Comparing with group A, GABA in group B were high and Glu were low(P<0. 01). Group C,D,E, F were better than group B(P<0.01). Group E was the best one. 4. In the group B, the expression of GABAA receptor in cortex significantly increased comparing with those in group A(P<0.01). While in the group C,D,E,F the expression of GABAA receptor were downregulated significantly comparing with those in group B(P<0.01), and group E decreased clearly. 5. In the group B, the expression of astroglia glutamate transporter GLASTmRNA in cerebral cortex were significantly decreased comparing with those group A, the expression of PTBRmRNA significantly increased comparing with those in group A(P<0.01), While in the group C,D,E,F, the expression of GLAST mRNA and PTBRmRNA were better than group B, and that group E havethe best effect.Conclusion The hyperammonia is a kind of basis pathogeneses of HEof type A. The abnormal expression of neurotransmitter caused byhyper ammonia plays an important role in the pathogenesis of HE.TheRuHuang Pill has its special effect by affecting the expression ofGABA/Glu,...