Effect of levothyroxine combined with donepezil hydrochloride in adult rats with hypothyroidism and its mechanism / 重庆医学

ABSTRACT

Objective To investigate the effect and potential mechanism of levothyroxine combined with donepezil hydrochloride in adulthood hypothyroidism rats.Methods A total of 60 male SD rats was divided by random number table into group A,group B,group C and group D,15 rats in each group.The rats in group B,group,C and group D were treated with PLT to prepare hypothyroidism model,and group A was used as the control group.After successful preparation of the model,rats in group C and group D were injected intraperitoneally with levothyroxine(6 g/100 g) every day,and then group D was given another 0.005％ donepezil in drinking water.After 2 weeks,the learning and memory behavior of rats was observed by Morris water maze;the levels of serum T3 and T4 were measured by radioimmunoassay;the expression of syntaxin-1 in hippocampus was detected by immunohistochemistry and Western blot.Results The escape latency and swimming distance of rats were prolonged significantly in group B but shorted significantly in group C and group D,and swimming speed was significantly slowed in group B but significantly strengthened in group C and group D;the levels of T3 and T4 were obviously decreased in group B but increased significantly in group C and group D,especially in group D.The results of immunohistochemistry and Western blot showed that the expression level of syntaxin-1 in hippocampus of rats was lower in group B compared to control group but increased significantly in both group C and group D.Conclusion Levothyroxine combined with donepezil hydrochloride can improve the learning and memory ability in adult rats with hypothyroidism,and its mechanism is related to the increase of expression of synaptotagmin-1 in hippocampus.