胰岛素抵抗对大鼠认知、ChAT活性及IGF-1的影响及吡格列酮的干预作用

Study of the effects and mechanisms of piogliazone on cognition function and vigor of choline acetyltransferase in insulin resistance in rats

目的探讨高果糖诱发的胰岛素抵抗大鼠认知功能、胆碱乙酰转移酶(choline acetyltrans-ferase,ChAT)活性及胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)的变化及吡格列酮的干预作用。方法从45只Wistar大鼠中随机选取10只作为对照组(NC组);其余35只以10%的果糖水诱发胰岛素抵抗;4周后根据胰岛素抵抗指数(insulin resistance index,IRI)将制作成功的胰岛素抵抗模型大鼠随机分为胰岛素抵抗组(IR组)和吡格列酮组(PIO组)。于干预12周末通过Morris水迷宫实验观察大鼠认知功能改变情况;采用化学比色法测定脑组织内ChAT活性;Western blotting检测脑组织IGF-1的表达;对脑组织切片进行尼氏染色。结果PIO组与IR组逃避潜伏期较NC组明显延长(分别为P<0.01,P<0.05),PIO组较IR组明显缩短(P<0.01);PIO组与IR组ChAT活性较NC组降低(P<0.01,P<0.01),PIO组较IR组增强(P<0.05);PIO组与IR组IGF-1表达较NC组降低(P<0.01),PIO组IGF-1表达较IR组增加(P<0.05)。结论吡格列酮对IR模型大鼠的学习记忆功能减退具有改善作用,其机制可能与促进神经元ChAT、IGF-1的表达,维持胆碱能神经功能正常有关。

Objective To explore the effects and mechanisms of pioglitazone on cognition function and vigor of choline acetyltransferase in insulin resistance （IR） rats. Methods 6-8-week-old Wistar rats were fed with fructose to develop insulin resistance model for 4 weeks. IR rat model was randomly divided into IR group （n = 13） and pioglitazone （PIO） group （n = 13）. Rats in PIO group were given pioglitazone 10 mg·kg^- 1 ·d^-1 by gavage for 12 weeks. The cognition ability of rats was assayed with Morris water maze test. The activity of choline acetyhransferase was detected by chemical coloration. Western blotting was performed to detect the expression of IGFI protein. Sections were stained with methyl aniline blue and cells in the hippocampal and cortex were observed with microscope. Results Morris water maze test showed that the escape latency was longer in IR group and PIO group than in NC group（P〈0. 01 ,P〈0. 05） ,and it was short in PIO group compared with IR group （P〈0. 01 ）. The expression of ChAT in IR group was lower than that in NC group. The expression of ChAT in PIO was increased significantly compared with IR group. The expression of IGF-1 protein in IR and PIO groups was lower than that in NC group（P〈0. 01,P〈0. 01 ）. Compared with IR group, the expression of IGF-1 in PIO group was significantly increased （P〈0. 05）. Conclusions Pioglitazone therapy can improve cognition functon in IR rat. This may be related to its effect of increasing the activation of ChAT and IGF-1.