甲状腺激素联合多奈哌齐治疗对成年甲减大鼠额叶SNAP-25的影响

目的 研究甲状腺激素联合多奈哌齐治疗对成年甲减大鼠额叶突触相关蛋白25(SNAP-25)的表达的影响.方法 将50只成年健康SD大鼠随机分为5组:对照组(CON)、甲减组(Hypo)、多奈哌齐组(DON)、左甲状腺激素钠组(L-T4)、左甲状腺激素钠联合多奈哌齐组(L-T4+DON);除对照组外,其余4组通过含0.05℅丙基硫氧嘧啶(PTU)饮用水喂养6周诱导成年期甲减大鼠模型;DON组、L-T4组、L-T4+DON组分别予多奈哌齐、左甲状腺激素钠、左甲状腺激素钠联合多奈哌齐治疗2周后,放射免疫法测定血清甲状腺激素水平,免疫组化法、Western blot法观察大鼠额叶SNAP-25的表达.结果 与CON组相比,Hypo组大鼠血清三碘甲状腺原氨酸(T3)、四碘甲状腺原氨酸(T4)水平显著降低(P<0.01),促甲状腺激素(TSH)显著上升(P<0.01);额叶SNAP-25的表达水平显著高于CON组(P<0.05).L-T4组与CON组比较,血清T3、T4、TSH差异无统计学意义;SNAP-25的表达升高(P<0.05).DON组与CON组比较,血清T3、T4、TSH差异有统计学意义(P<0.01);SNAP-25的表达升高(P<0.05).L-T4+DON组与CON组比较,血清T3、T4、TSH差异无统计学意义;SNAP-25的表达差异无统计学意义.结论 甲状腺激素联合多奈哌齐治疗能有效地恢复成年甲减大鼠额叶SNAP-25的表达.

Effects of donepezil combined with thyroxine on frontal SNAP-25 expression in adult rats with hypothyroidism

Objective To study the effect of thyroxin combined with donepezil on the expression of the frontal syn-aptosomal associated protein of 25 ku(SNAP-25) in adult rats with hypothyroidism. Methods 50 healthy adult SD rats were randomly divided into 5 groups:control group ( CON ) , hypothyroidism group ( Hypo ) , donepezil group (DON), levothyroxine sodium group(L-T4), levothyroxine sodium combined with donepezil group(L-T4+DON). In addition to the control group,the hypothyroid adults rats of the other groups were induced by the drinking water including 0. 05℅ propylthiouracil(6-n-propyl-2-thiouracil, PTU) for six weeks. Then, the latter three groups were treated respectively with donepezil, levothyroxine sodium and levothyroxine sodium combined with donepezil for 2 weeks. The radioimmunoassay kit was used to determine the levels of serum T3,T4,TSH. The immunohistochemical method and Western blot were used to observe the frontal SNAP-25 expression in all rats. Results Compared with the control group, serum triiodothyronine(T3) and tetraiodothyronine(T4) levels in hypothyroid rats decreased sig-nificantly(P<0. 01), thyroid-stimulating hormone(TSH)(P<0. 01) increased significantly, and the expression level of SNAP-25 in frontal lobe was significantly higher than that in the control group ( P<0. 05 ) . There was no statistically significant difference in serum T3 , T4 and TSH between the L-T4 group and the control group and the expression of SNAP-25 in L-T4 group was increased(P<0. 05). In the DON group, the serum T3, T4 and TSH were statistically significantly increased(P<0. 01), compared with the control group and the expression of SNAP-25(P<0. 05) was higher. The comparison of serum T3, T4, TSH levels and the expression of SNAP-25 were not statistically significant. Conclusion The treatment of thyroxin combined with donepezil can effectively recover the expression of frontal SNAP-25 in adult rats with hypothyroidism.