Apoptosis Of Neurocyte Induced By Ammonia In Liver Cirrhosis Rat

AIMAmmonia is a kind of major abnomal metabolite in patients with hepatic encephalopathy ( HE) and hyperammonemia plays a pivotal role in HE. It had been proved that ammonia may enhance more neuro-nal apoptosis in vitro. The relationship between ammonia and neuro-cyte apoptosis in animal model has not been reported. The aims of the stuty were to observe the apoptosis of neurocyte induced by ammonia in the rat model with haptic cirrhosis.MATERIALS AND METHODSMale wistar rats initially weighing 180 -220g were used and were randomly divided into 4 groups which were treated by 4 different treatments : (1)nomal control group : distilled water was given at the end of experiment; (2)normal ammonia control group:ammonia was given at the end of experiment; (3)experimental cotrol group; the rats were given carbontetrachloride ( CC14) to get rat models. Distilled water was given at the end of experiment; (4) experimental group: After prepera-tion of liver cirrhosis rat model , ammonia was given at the end of experiment. 0. 6ml blood samples were collected before and 20 minutes after ammonia admistration. During 2 hours after ammonia admistra-tion,we observe whether the rats companied with HE by righting and corneal reflexes. Before killing the rats, 1ml blood samples were stillcollected to detect ALT, ASTand TBil. Immediately after killing the rats, liver and brain tissues were collected in order to observe the his-tological changes by telescope. The apoptotic cells were accessed by the TUNEL staining and the apoptosis index (AI) were caculated.RESULTSThree rats in experimental guoup were found without righting and corneal reflexes, which showed HE occurred. These reflexes occur in the other three control guoups. The levels of ALT, ASTand TBil in liver cirrhsis rat models were higher than those of nomal control groups. The levels of blood ammonia in 0 minitue in the group (3)and(4)were already higher than those of the group (1), furthermore, the levels of blood ammonia in 20 minitue in experimental group were much higher than the other 3 groups, which showed the levels of ammonia in liver cirrhosis rat had elevated and it significantly rose after treating with ammonia(P <0. 01) . The levels of AI in experimental control guoup were higher than those of normal control group and the levels of AI in experiment guoup were higher than those of the other 3 groups, the differences were significant( P <0. 01).DiscussionHE is a neuropsychiatric syndrome frequently observed in chronic liver falure. The pathogenesis of chronic HE is not fully clear, although the condition is believed to be a multifactoral origin. HE is characterized by neurological alteration, animal behavioral perturbations and metabolic perturbations. Elevated blood ammonia is one of the well ?known pathogenic factors in HE. Many researches believe that ammonia can disturb the energy metabol, effect the activities of Na+ - K+ -ATP enzyme and disturb the banlance of the neurous massengers. It had been reported that some molecule of inducing apoptosis have a binding site for adenosine 5' triphosphate( ATP) ,which might explain ammonia is an important factor in neurocyte apoptosis. Our study demonstrated that the level of ammonia had raised in liver cirrhosis rat and it significantly raises after giving ammonia.The death of neurocyte has two ways: necrosis and apoptosis, depending on the genie context and cause of death. Apoptosis, a more subtle, noninflammatory, energy - dependent form of cell death, has recently been noticed by many authors. Recent research on the molecular mechanisms of apoptosis has indicated that apoptosis is a genetically programmed process that can become deranged when the components of the celluar apoptosis machinery are mutated or present in inappropriate quantities. Dysregulation of apoptosis is associated with the pathogenesis of a wide array of diseases. Apoptotic cell death and its attendant molecular mediators appear to play a role in many neurode-generative disorders, including Alzheimer disease, Park...