摘要
目的探讨盐酸吡格列酮通过提高海马区海马胆碱能神经刺激肽（HCNP）含量，对改善2型糖尿病模型大鼠空间记忆能力的作用及其机制。方法12周龄雄性SD大鼠按照随机数字表法分为对照组、2型糖尿病组（DM组）、2型糖尿病＋盐酸吡格列酮组（DP组），每组12只。对照组大鼠普通饲料喂养，DM组大鼠给予高脂饮食，DP组大鼠高脂饮食20周基础上给予盐酸吡格列酮10mg／（kg·d）干预8周，每日1次灌胃给药。对照组、DM组同期2mL生理盐水灌胃。采用水迷宫实验检测3组大鼠空间记忆能力：Westernblotting法检测3组大鼠海马组织中HNCP前体蛋白（HCNP．PP）含量（以此反映HCNP蛋白含量）；逆转录PCR方法检测HCNP—PP、胆碱乙酰基转移酶（CHAT）、1型毒蕈碱样受体（M1R）、α7型烟碱样受体（αTNR）mRNA表达水平。结果（1）DM组大鼠逃避潜伏期延长，与对照组、DP组比较差异有统计学意义（P〈0．05）。（2）与对照组和DP组相比，DM组大鼠海马HNCP-PP蛋白含量及mRNA相对水平升高，HNCP蛋白含量减少，ChAT、M．R及α7NRmRNA相对含量均下降，差异均有统计学意义（P〈0．05）。结论盐酸吡咯列酮通过促进HCNP—PP裂解致HCNP增多．进一步作用于相关胆碱能神经受体，以此改善2型糖尿病模型老年大鼠空间记忆能力。
Objective To demonstrate the effect of Pioglitazone hydrochloride on spatial memory ability in diabetes rats via improving the level of hippocampal cholinergic neurostimulating peptide （HCNP） in the hippocampus tissues. Methods Twenty-four 12-week old male SD rats were equally randomized into control group （Con）, diabetes group （DM）, DM＋Pioglitazone hydrochloride treatment group （DP）. Rats of the DM and DP groups were fed with high fat diet, and rats of the DP group were also performed intragastric administration of 10 mg/（kg·d） Pioglitazone hydrochloride daily. Morris water maze test was performed on the rats enjoyed successful model making to detect their spatial memory ability; the level of HCNP precursor protein （HCNP-pp） was measured by Western blotting so as to measure the level of HCNP; and the relative mRNA contents of HCNP-pp, choline acetyltransferase （CHAT）, muscarinic receptor 1 （MIR） and α7 type nicotinic receptor （α7TNR） genes were measured by reverse transcription PCR. Results The escape latency in rats of the con and DP groups was significantly shortened as compared with that in the DM group （P〈0.05）. As compared with that in the Con and DP groups, the relative amount of HCNP-pp in DM group was higher in protein and mRNA levels （P〈0.05）; however, the relative amount of HCNP in the DM group was obviously lower than that in the Con and DP groups （P〈0.05）. And the mRNA CHAT, M1R and α7TNR levels in the Con and DP groups were significantly higher than those in the DM group （P〈0.05）. Conclusion Pioglitazone hydrochloride can accelerate the lysis of HCNP-pp in the hippocampus to induce the increased level of HCNP, further making the cholinergic nerve receptors activation, which maybe one of the mechanisms to improve the ability of spatial memory in eldly rats with type 2 diabetes.
出处
《中华神经医学杂志》
CAS
CSCD
北大核心
2012年第9期882-886,共5页
Chinese Journal of Neuromedicine
基金
广州市番禺区科技计划项目（2010-Z-98-1）
关键词
盐酸吡咯列酮
糖尿病
空间记忆
海马胆碱能神经刺激肽
Pioglitazone hydrochloride
Diabetes mellitus
Spatial memory
Hippocampal cholinergic neurostimulating peptide
