老龄帕金森病模型小鼠氧化应激相关基因的表达差异.pdfVIP

tetraiodothyronine(T4),thyroid-stimulating hormone(TSH) were measured by radioimmunoassay kits, acetylcho- line concentration in frontal lobe was determined by alkaline hydroxylamine colorimetry and the expression and dis- tribution of munc-18 in frontal cortex were evaluated by immunohistochemistry. Results In the hypothyroid rats,the levels of serum T3 and T4 decreased with the increase of TSH(P 0． 01), the content of acetylcholine in frontal lobe was significantly decreased(P 0． 05),and the expression of munc-18 was at significantly lower levels in the Ⅱ,Ⅲ,Ⅳ,Ⅴ layers of frontal cortex (P 0． 05). In addition, donepezil treatment reversed the content of acetyl- choline to normal values. L-T4 monotherapy normalized the level of serum thyroid hormone and acetylcholine con- tent while the expression of munc-18 was not. Munc-18 was normalized completely by co-administration of L-T4 and donepezil. Conclusion The alteration of acetylcholine content and expression of munc-18 in the frontal lobe of a- dult-onset hypothyroidism can be better ameliorated by co-administration of L-T4 and donepezil. Key words hypothyroidism;frontal cortex;acetylcholine;munc-18; levothyrocine; donepezil 老龄帕金森病模型小鼠氧化应激相关基因的表达差异 马晓伟,张忠霞,王彦永,李晓丽,王铭维 摘要 目的 探讨老龄帕金森病(PD)模型小鼠行为学改变 及黑质纹状体系统氧化应激相关基因的表达差异 方法 10 月龄快速老化 P8 系(SAMP8)小鼠 16 只,随机均分为对 照组和模型组 模型组小鼠背部皮下注射 1 甲基 4 苯基 1, 2,3,6 四氢吡啶(MPTP)制成急性损伤模型,对照组小鼠给 予同量生理盐水 给药后 72 h 进行行为学测试,高效液相 色谱法检测黑质多巴胺(DA)含量,PCR Array检测其纹状体 氧化应激相关基因的表达 结果 与对照组相比,模型组小 鼠 DA水平下降,行为学成绩下降,差异有统计学意义(P 0． 01);环氧化酶 2 可诱导型一氧化氮合酶 2 还原型烟酰胺 腺嘌呤二核苷酸磷酸(NADPH)氧化酶基因表达上调;而谷 胱甘肽过氧化物酶 3 6 8 等 9 种基因明显下调(改变倍数 2) 结论 老龄 PD模型小鼠氧化应激相关的基因发生上调 或下调,导致氧化应激反应的发生 关键词 老龄;帕金森病;氧化应激;SAMP8;MPTP 中图分类号 R 742. 5 文献标志码 A 文章编号 1000 1492(2015)01 0029 04 老化是导致帕金森病( parkinson disease, PD) 的主要危险因子之一 随着社会的老龄化,PD的发 20 4 09 24 接收 基金项目:河北省医学科学研究重点课题计划 (编号:20 0302、 20 30272) 作者单位:河北医科大学第一医院神经内科,河北省脑老化与认知神 经科学实验室,石家庄 05003 作者简介:马晓伟,女,硕士,副主任医师; 王铭维,女,教授,主任医师,博士生导师,责任作者,E- a l: w w@ heb u edu cn 病率也逐年增长 快速老化小鼠(senescence-ac