Effect Of L-NNA On The Activity Of NOS And NOS Positive Neurons In The Brain Of Rabbits With Chronic Alcoholism

The animal model of chronic alcoholism was established in rabbits, NOS inhibitor L-NNA and naloxone were respectively used to treat the successful animal model. We researched the relationship between brain damage of chronic alcoholism and NO, the effect of NOS inhibitor L-NNA on NO, NOS levels in injured brain tissue by measuring the activity of NOS, the content of NO and the changes of nNOS positive neurons in frontal,hippocampus and striatum in every group of rabbits. The study could provide theoretical basis for clinical treatment and theoretical basis for mechanism of chronic alcohol brain damage and pathology research.The model of chronic alcoholism was established by giving alcohol with rabbits, and determined by weight, behavior changes and Histopathological in the brain of rabbits. After 6weeks, the weight of rabbits fed alcohol was negative. Histopathological observation showed that the neuron loss occurred in brain of rabbits with chronic alcoholism after eight weeks.The neuron loss and cytolysis were significantly observed with the increase of time, and pyramidal cells in hippocampus were arranged in disorder. The changes of nNOS and i NOS in different regions were confirmed the reliability of the model.The activity of NOS and the content of NO in frontal, hippocampus and striatum in every group of rabbits were determined by the method of nitric acid reductase and biochemical method. Results: The activity of NOS in brain of model group was keeping rising, and it was significantly higher than that of the control group all the time, the changes of NO content in brain of model was as the same as the changes of NOS. The levels of NOS and NO increased slowly after the treatment with naloxone and L-NNA, three days later the NOS and NO levels decreased, then tended to be stable. The activity of NOS and NO contents in brain of treatment groups were significantly lower than that of model group.TNOS and iNOS positive neuron in frontal, hippocampus and striatum were observed byimmunohistochemistry. Results: TNOS and iNOS positive neurons expression’ order was consistent with NO and NOS levels in brain tissues of every group. The expression of NOS positive neurons in brain of ethanol group was significantly higher than that of control group,and the expression of NOS positive neurons in brain of three treatment groups were lower than ethanol group, the decrease amplitude of the combined group was the largest.The results indicated that the missing and death of neurons in frontal, hippocampus and striatum of rabbits with chronic alcoholism were accompanied by increases of NO content in brain tissue and the expression of nNOS and iNOS in brain. NO level and the expression of nNOS and iNOS positive neurons were decreased after the treatment with L-NNA and naloxone. The results showed that the mechanism of the brain damage in alcohol rabbits was mediated by NO, the activity of NOS was inhibited by naloxone and L-NNA to provide the brain tissue of rabbits with chronic alcoholism. The inhibitor of NOS provides a new direction for clinical treatment of chronic alcoholism and drug development.