南方医科大学学报

南方医科大学学报 ›› 2013, Vol. 33 ›› Issue (10): 1463-.

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PPARγ在神经系统中能够促进IRS-4 基因表达

章红妍，蒙思颖，林利芳，吴巧琪，周日阳，王雪敏   

  • 出版日期:2013-10-20 发布日期:2013-10-20

Effects of peroxisome proliferator-activated receptors γ on the expression of insulin receptor substrate-4 gene in rat cortical neurons and mouse brain

  • Online:2013-10-20 Published:2013-10-20

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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。

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 PPARγ agonist 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 the control
group. The expression of IRS-4 mRNA was significantly up-regulated in the cortical tissues and neurons of the agonist groups
compared with the control groups (P<0.05), but in BKO mice without treatment, IRS-4 mRNA expression was significantly
down-regulated (P<0.05). Conclusion PPARγ can enhance the expression of IRS-4 mRNAin the brain.