Effects Of Levothyroxine Sodium Combined With Donepezil On Expression Of SNAP-25 In Posterior Cingulate Gyrus Of Adult Hypothyroidism Rats

Objective1.To observed the expression of synaptic associated protein 25 in the posterior cingulate gyrus of adult rats with hypothyroidism(abbreviated as hypothyroidism)2.To study the effect of combination therapy of L-T4 and DON on the expression of synaptic associated protein 25(SNAP-25)in posterior cingulate gyrus of hypothyroidism rats.Methods Forty healthy male SD rats were divided into normal control group(CON group),hypothyroid group(Hypo group),L-T4 substitution group(L-T4 group),donepezil treatment Group(DON group),combined therapy group(L-T4 + DON group)by random number table method after adaptive feeding.The rats were treated with 0.05%propylthiouracil(PTU)for 6 weeks to establish a hypothyroidism model except for the CON.5 weeks after the model establishment,levothyroxine sodium,donepezil,levothyroxine sodium and donepezil were given for 2 weeks.The levels of serum thyroid hormones were measured by radioimmunoassay.The number of Nissl bodies was observed by Nissl’s staining method.Immunohistochemistry and Western blot were used to observe the expression of SNAP-25.Results1.Thyroid function in each group: The levels of serum thyroxine in the Hypo and DON group were significantly lower than those in the CON(P <0.01).There was no significant difference between the LT4 and the LT4 + DON group as well as the CON.2.Expression of Nissl body in each group: The number of Nissl bodies in Hypo group was decreased as compared to the CON(P< 0.05),while the L-T4 and DON increased the number of Nissl bodies in the hypothyroid rats(P< 0.05),however,it was still lower than that in CON(P< 0.05).And interestingly,there was no marked significance between the number of Nissl bodies and AOD value for the Nissl staining of L-T4+DON and CON.3.The expression of SNAP-25 protein in each group: The expression of SNAP-25 was significantly up-regulated in the hypothyroid or the DON treated rats than that in CON(P <0.05),the L-T4 had low expression than Hypo(P< 0.05)and had not restored the SNAP-25 expression when comparing with CON(P< 0.05).While of note,the level of SNAP-25 was not altered with compared to the CON.Conclusion1.The expression of SNAP-25 protein in posterior cingulate gyrus was increased in adult hypothyroid rats(P <0.05),with the number of Nissl body reduced.2.The combined treatment of levothyroxine sodium and donepezil could effectively protect the synaptic protein and Nissl body against injury.