| Alcoholic is the worldwide problem which do harm to the public health.The production and consumption of alcohol have increased in recent years, the prevalence of chronic alcoholism have an upward trend too. Chronic alcoholism can caused damage to the nervous system, which including Wernicke Encephalopathy, Korsakoff Syndrome, Cerebellar degeneration with alcoholism, Central Pontine Myelinolysis, and so on,but peripheral nerve have the highest incidence.There are many animal model of alcoholism , however, most of these models are used to study the role of alcohol on heart, brain, liver, pancreas and other organs. Which are less to the study of peripheral neuropathy of chronic alcoholism.Most of the methods are gavage and intraperitoneal injection. It is necessary to find out an animal model which are similar with the pattern of human drinking .So that we can provide an ideal model of basic and clinical research on the peripheral neuropathy of chronic alcoholism. we referenced to the free-drink model which are recognition in the foreign,and established a new type model on peripheral neuropathy of chronic alcoholism.CTP is one of drugs of nucleotide,the main pharmacodynamics ingredients of its is cytidine.CTP participate in the synthesis and metabolism of nucleic acid and phospholipid and promote the synthesis of protein.CTP can regulate the synthesis and modification of the membrane structure of the nerve by affectting the synthesis of phospholipid.CTP can support the activity of nerve cell, promote the regeneration of nervous process and improve the ability of anti-injury.Encephalin and lecithin are the main components of cell membranes.CTP involve in the synthesis of nucleic acid and glyceroph- osphatide directly ,and involve in the synthesis of phospholipid by various channels, so it has played an important role in improving the synthesis of nerve cell membrane.CTP can promote repair and regeneration of nerve cells, protect the structure of cell membrane and the blood-brain barrier, and provide the necessary energy of the nerve cells effectively.CTP may also enhance the biological activity of nerve cells, and can fight the damage of the nerve cells which are caused by excitatory amino acids and free radical. We planed to provide a stable ,reliable, reproducible and new animal model of peripheral neuropathy of chronic alcoholism, study of the role of CTP on peripheral neuropathy of chronic alcoholism.We use 40 healthy male Wistar rats as our animal models of peripheral neuropathy of chronic alcoholism.The rats were divided into four groups randomly.Control group, alcohol group, placebo group and treatment group. Both the alcohol group and the control group had 15 rats.The placebo group and the treatment group had 5 rats.Each group were given common food. The control group drink water.The alcoholic concentration of the alcohol group, the placebo group ,and the treatment group were increased from 6%,9%,12% to20% every five days,and the rat were breed with 20% alcoholic concentration until the end. The placebo group were given intraperitoneal injection of 7.2mg/kg/d of 0.9% sodium chloride solution,and the treatment group were given intraperitoneal injection of 7.2mg/kg/d of CTP from the beginning of the four month,which continued four weeks. They were measured weight every week and record the quantity of drink and food every other day. The rat of control group and alcohol group were examined with EMG by the end of two, three, and four month.After that ,they were killed.The sciatic nerve and L4, 5,6 ganglion were kept for pathology. The rat of placebo group and treatment group were examined with EMG and pathology by the end of four month. The experimental results are as follows:1.weight and diet changes:Both weight and appetite decreased in alcohol group, placebo group, treatment group rat than that of control group.Weight of the rats of alcoholism group,placebo group,and treatment group began to decrease at 3 weeks, and reach to the minimum at 4 weeks, and resume to increase at 7weeks. But,it increased slowly compared with control group.2.EMG changes: Electrophysiologically the alcohol group rat showed slow motor conduction velocity(MCV) and low amplitude compound muscle action potentials(CMAP) by the end of four month, compared with control group. The placebo group rat showed slow MCV and low CMAP, compared with control group rat. Which had no obviously different with treatment group and control group. But the treatment group showed fast MCV and high CMAP, compared with placebo group.The difference was statistically significant.3.Pathological changes:Under the light microscope, both HE and silver stain of sciatic nerve of the rat at two and three month are normal,compared the alcohol group with the control group. Both HE and silver stain of sciatic nerve of the rat at fouth month end in light microscope showed axonal swelling,thickness ranges accompany with secondary segmental demyelination. Both HE and toluidine blue stain of sciatic ganglia showed non apparent abnormality.Under electron microscope , the structure of sciatic nerve of the rat of alcohol group at two month end did not change significantly compared with the control group.It formed a small vacuoles in mitochondria of axonal in the alcohol group by the end of three month,but the myelin did not change.In the sciatic nerve of the rat of alcohol group by the end of four month , axonal were swelling and some of them disappearing,mitochondrial changed like vacuolar,the quantities of the neurofilaments, microtubules and microfila- ments were less,and the structure of them were unclear.myelin were thicken,layers were separation ,and some of them were lysis. Sciatic nerve of the placebo group rat in light microscope showed axonal swelling and thickness ranges accompany with secondary segmental demyelination,but the treatment group had a slight change compared with the placebo group,and the control group were normal.It suggested that CTP were effective on the treatment of peripheral neuropathy of chronic alcoholism.4.Norphometry analysis:Analyzed by norphometry after toluidine blue stain of sciatic nerve ,area changes of transverse section of myelinated nerve fiber of the alcohol group showed significant difference, compared with the control group by the end of three and four month,but there were no obviously changes by the end of two month.It suggested that small dimension fiber were more sensitivity.In short, the free-drink model of CAPN on rat has the advantagesas follow:It can avoid the trauma to the animals by the methods of gavage and intraperitoneal injection,reduce mortality and improve survival time.A gradual increase in the concentration of alcohol, animal can adapt well,and have high stability of model.The model have no invasive, so it can ensure that an adequate supply of alcohol with full time.The changes of EMG and pathology on rat are consistent with the peripheral neuropathy of chronic alcoholism on human beings,So it can be used for basic and clinical research.By studing of the model We also found out that the changes of EMG and pathology were different because the time of drinking of rat were different.We can use the inspection methods of EMG (self-control) periodicly to screening subclinical peripheral neuropathy of chronic alcoholism, in order to select the best opportunity of treatment.CTP has the ability of anti-injury. CTP can regulate the synthesis and modification of the membrane structure of the nerve. CTP can support the activity of nerve cell, promote the regeneration of nervous process.It have good effect on the treatment of peripheral neuropathy of chronic alcoholism,and can be used as a new type of drug and treat CAPN. It have less reporting and broad clinical application at home and abroad. |
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