PPARγ在神经系统中能够促进IRS-4基因表达.pdf

J South Med Univ, 2013, 33(10): 1463-1466 doi 10.3969/j.issn. 1673-4254.2013.10.11 1463· · 基础研究 PPARPPARγγ在神经系统中能在神经系统中能够促进够促进IRS-IRS-44 基因表达基因表达 章红妍，蒙思颖，林利芳，吴巧琪，周日阳，王雪敏 南方医科大学基础医学院神经生物学教研室，广东 广州 510515 摘要：目的探讨过氧化物酶体增殖物激活受体γ（PPARγ）对脑内胰岛素受体底物-4（IRS-4）基因表达的影响。方法体外实验采 用原代培养1周的大鼠皮层神经元，用10 μmol/L PPARγ激动剂罗格列酮分别处理0、1、4、24 h ；体内实验选取成年C57BL/6J 小 鼠和脑内PPARγ条件性敲除（BKO）小鼠，分别按12 mg/kg 腹腔注射罗格列酮（10% DMSO 溶解）或同等剂量10% DMSO 作用 12 h。利用MTT 法检测原代培养皮层神经元存活率；实时定量PCR 法检测神经元及皮层组织内IRS-4 mRNA 的变化情况。结 果各处理组皮层神经元存活率与对照组相比无显著性差异；罗格列酮处理的皮层神经元，C57BL/6J 小鼠和BKO 小鼠皮层内 IRS-4 mRNA 水平较对照组均明显增高；未处理的BKO 小鼠皮层内IRS-4 mRNA 水平较对照组显著降低。结论PPARγ在神经 系统中能够促进IRS-4 表达。 关键词：大脑皮层；罗格列酮；过氧化物酶体增殖物激活受体γ；胰岛素受体底物-4 Effects of peroxisome proliferator-activated receptors γon the expression of insulin receptor substrate-4 gene in rat cortical neurons and mouse brain ZHANG Hongyan, MENG Siying, LIN Lifang, WU Qiaoqi, ZHOU Riyang, WANG Xuemin Department of Neurobiology, Southern Medical University, Guangzhou 510515, China Abstract: Objective To investigate the effect of peroxisome proliferator- activated receptors γ (PPARγ) on insulin receptor substrate- 4 (IRS-4) gene expression in the brain. Methods Primarily cultured cortical neurons from E17- 18 Sprague Dawley rats, after 1 week of plating, were exposed to 10 μmol/L PPARγagonist rosiglitazone for 0, 1, 4 or 24 h. Adult C57BL/6J mice or conditional brain PPARγ knock- out mice (B- PPARγ- KO, BKO) received an intraperitoneal injection of rosiglitazone in 10% DMSO at 12 mg/kg or injection of the same volume of saline containing 10% DMSO. The effect of rosiglitazone on the survival of the neurons was examined by MTT assay. The expression of IRS- 4 mRNA was analyzed by real- time quantitative PCR. Results The survival of the cortical neurons showed no significant difference between the agonist groups and t