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|本期目录/Table of Contents|

高胰岛素状态下巨噬细胞PPARγ抗炎活性的变化(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2006年第1期
页码:
14-17，27
栏目:
基础研究
出版日期:
2006-01-01

文章信息/Info

Title:
Changes in macrophage PPAR gamma antiinflammatory activities under high insulin levels
作者:
张俊峰1; 葛恒1; 郭炳诗2; 王长谦1
1.上海交通大学医学院附属第二医院心内科，上海 200001；2.上海第二医科大学/中国科学院上海生命科学院健康科学中心，上海 200025
Author(s):
ZHANG Jun-feng1; GE Heng1; GUO Bing-shi2; WANG Chang-qian1
1.Department of Cardiology，Renji Hospital，Shanghai Jiaotong University，Shanghai 200001，China； 2. Health Science Center， Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Second Medical University, Shanghai 200025，China
关键词:
胰岛素; 巨噬细胞; 过氧化物酶体增殖物激活受体; 炎症
Keywords:
insulin;  macrophage;  peroxisome proliferatoractivated receptors;  inflammation
分类号:
R329.26
DOI:
-
文献标识码:
A
摘要:
目的 探讨高胰岛素状态下巨噬细胞过氧化物酶体增殖物激活受体γ（PPARγ）抗炎活性的变化。方法 体外培养THP1细胞，诱导分化为巨噬细胞，采用吡格列酮和不同浓度胰岛素分组干预，ELISA法测定细胞培养上清液中IL-6、TNF-α、MMP-9浓度，Gelatin Zymography法测MMP9活性。半定量RTPCR、Western blot检测巨噬细胞PPARγ基因、蛋白表达。结果 PPARγ配体吡格列酮（20 μmol/L）作用24 h可显著降低巨噬细胞IL-6（P<0.01）、TNF-α、MMP-9的分泌(P<0.05)，抑制MMP9活性(P<0.05)。高胰岛素使吡格列酮抑制巨噬细胞分泌IL6、TNFα、MMP-9的作用减弱，此作用与胰岛素浓度有关，呈浓度依赖性（0.25~0.5 μmol/L）。而高胰岛素（0.1 μmol/L）状态下巨噬细胞PPARγ基因、蛋白的表达均无显著变化。结论 高胰岛素可减弱PPARγ配体抑制巨噬细胞分泌IL6、TNFα、MMP-9的作用，但并未对巨噬细胞PPARγ基因、蛋白的表达产生影响，提示胰岛素对PPARγ的活性可能存在抑制。
Abstract:
AIM To investigate the changes of the antiinflammatory activities of macrophage PPAR gamma under high insulin levels. METHODS Human monocytic cell lines THP-1 were cultured and then induced into macrophage by PMA treatment. The differentiated monocytes were then cultured in medium of insulin at different concentrations treated with or without piogiltazone. IL-6, TNF-α and MMP-9 levels in cell culture medium were measured by ELISA. MMP-9 activities were determined by gelatin zymography. Macrophage PPARγ mRNA and protein expression were detected by semiquantitative RTPCR and Western blot, respectively. RESULTS Pioglitazone（20 μmol/L） treatment for 24 hours significantly decreased the secretion of IL6 (P<0.01), TNF-α and MMP-9 (P<0.05) from macrophages as well as inhibited MMP-9 activity (P<0.05). High insulin（0.25 μmol/L）partly counteracted the inhibitory action of pioglitazone on macrophage secretion of IL6, TNFα and MMP-9 in a concentrationdependent manner. High insulin（0.1 μmol/L）treatment had no significant effect on macrophage PPARγ mRNA or protein expression. CONCLUSION High insulin can counteract the inhibitory action of PPARγ agonists on macrophage secretion of IL-6, TNF-α and MMP-9, but has no significant effect on macrophage PPARγ mRNA or protein expression, suggesting that insulin may inhibit the activity of PPARγ.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2004-08-20.基金项目：国家自然基金项目资助(No.30070869) 通讯作者：王长谦，主任医师，博士Email:wcqian@hotmail.com 作者简介：张俊峰，主治医师，硕士 Tel：（021）566911016260 Email：zhangjf1222@yahoo.com
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