The Effects Of Thyroxine Combined With Donepezil On Expression Of Synaptotagmin-1 In The Prefrontal Cortex Of Rats With Hypothyroidism

Objective Hypothyroidism can cause structural damage which is involved in synaptotagmin-1 expression within the prefrontal cortex.Thyroxine replacement therapy of clinical criteria may not make the damaged protein whithin prefrontal cortex recover to normal levels.This experiment aimed to study the treatment effects of thyroxine combined with donepezil for the synaptotagmin-1 expression levels in the prefrontal cortex of rats with hypothyroidism.Methods Selected 50 healthy Sprague-Dawley rats meanwhile ensured the unified standard for 10 weeks of age?male and clean level.According to the difference of drug treatment factors,the rats were randomly divided into 5 groups: normal control group,hypothyroid group,donepezil treatment group,thyroxine treatment group,thyroxine combined with donepezil treatment group.The rats of normal control group were fed with clean running water for 6 weeks,while the other four groups were fed with 0.05% propylthiouracil water for 6 weeks to establish hypothyroidism model.From the fifth week,the concentration of 0.005%(W/V)of donepezil was added to the drinking water of the donepezil treatment group.T4 group was given intraperitoneal injection of sterile saline at a concentration of 6ug/100 g,and the rats of thyroxine combined donepezil treatment group were given the above methods.simultaneously,the normal control group,hypothyroid group and donepezil treatment group were given the same volume intraperitoneal injection of sterile saline.Analyzed the syt-1 expression level within the prefrontal cortex of rats by Western blot.Analyzed the immune reaction product distribution and expression level of syt-1 in the prefrontal cortex of rats by allergic immunohistochemical method.Result 1.Serum thyroid hormone levels of each group rats: The serum thyroid hormone levels of hypothyroidism and donepezil treatment groups were lower than control group(p< 0.05),but the difference of thyroxine and combined groups had no statistical significance compared with control group.2.syt-1 expression level within the prefrontal cortex of each group rats: The expression levels of syt-1 within the prefrontal cortex of hypothyroidism group?donepezil group and thyroxine group were higher than control one(p< 0.05),but returned to the normal level in combination therapy group.3.Expression and distribution of syt-1 within prefrontal cortex each layer of each group rats : The immune reaction product of syt-1 was brownish granules which was widely distributed in the prefrontal cortex of rats by allergic immunohistochemical method by hypersensitivity immunohistochemistry,but there was a difference in the content of brown particles between groups.By using the optical microscope,there were 5-layer structure of the prefrontal cortex of rats from outside to inside including:molecular layer,outer particle layer,outer pyramidal cell layer,inner particle layer,inner pyramidal cell layer.The immune reaction product level of syt-1 within the prefrontal cortex each layer of hypothyroidism group?donepezil group and thyroxine group were higher than the corresponding layers control one(p< 0.05),but returned to the normal level in combination therapy group.Conclusion 1.Hypothyroidism can cause the improvement of syt-1 expression within prefrontal cortex of rats.2.The damaged of molecular level within the prefrontal cortex of rats with hypothyroidism after replacement therapy can be improved,but after treatment with thyroxine,the damage of the expression level of syt-1 whithin the prefrontal cortex of hypothyroidism rats can't fully recover.3.The damaged of syt-1 expression level in the prefrontal cortex of rats induced by hypothyroidism was completely recovered by thyroxine combined with donepezil treatment.