上海交通大学学报（医学版）

›› 2012, Vol. 32 ›› Issue (7): 861-.doi: 10.3969/j.issn.1674-8115.2012.07.009

• 论著（基础研究） • 上一篇    下一篇

PPARγ激动剂对单核细胞炎症反应的调控作用

王 静1, 徐 萍1, 侯彦强2, 娄晓丽2, 黄 玲1   

  1. 上海交通大学附属第一人民医院松江分院 1.消化内科, 2.中心实验室, 上海 201600
  • 出版日期:2012-07-28 发布日期:2012-08-17
  • 通讯作者: 徐 萍, 电子信箱: yfyxp@yahoo.com.cn。
  • 作者简介:王 静（1981—）, 女, 主治医师, 硕士；电子信箱: wangj0081@126.com。
  • 基金资助:

    上海市自然科学基金（09ZR1429100）和上海市松江区卫生局医学领先合作项目（201101）

Regulation of inflammatory response in monocytes by PPARgamma agonist

WANG Jing1, XU Ping1, HOU Yan-qiang2, LOU Xiao-li2, HUANG Ling1   

  1. 1.Department of Gastroenterology, 2.Central Laboratory, Songjiang Central Hospital, the First People´s Hospital, Shanghai Jiaotong University, Shanghai 201600, China
  • Online:2012-07-28 Published:2012-08-17
  • Supported by:

    Natural Science Foundation of Shanghai, 09ZR1429100；Shanghai Songjiang District Health Bureau Foundation, 201101

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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）激动剂对单核细胞炎症反应的影响。方法 体外培养THP-1人单核细胞，将细胞分为对照组、实验组、吡格列酮组和GW9662组。对照组仅加入细胞培养液；实验组用胰腺炎相关性腹水（PAAF）刺激细胞；吡格列酮组在PAAF作用前加入终浓度为20 μmol/L的PPARγ激动剂吡格列酮进行干预；GW9662组：在吡格列酮干预前30 min，先行加入PPARγ拮抗剂GW9662，最后加入PAAF。分组处理6 h后收集各组细胞，采用Real-Time PCR技术检测促炎症细胞因子肿瘤坏死因子α（TNF-α）和白介素6（IL-6）mRNA的表达；分别采用RT-PCR和Western blotting法检测PPARγ mRNA和蛋白的表达。结果 PAAF刺激后，与对照组比较，实验组、吡格列酮组和GW9662组细胞TNF-α和IL-6 mRNA的相对表达量明显升高，PPARγ mRNA的相对表达量明显降低，差异均有统计学意义（P<0.05）；与实验组比较，吡格列酮组TNF-α和IL-6 mRNA的相对表达量明显降低，PPARγ mRNA的相对表达量明显升高，差异均有统计学意义（P<0.05）；与吡格列酮组比较，GW9662组TNF-α和IL-6 mRNA的相对表达量均明显升高，PPARγ mRNA的相对表达量明显降低，差异也有统计学意义（P<0.05）。Western blotting检测结果显示：各组PPARγ的蛋白表达与mRNA表达的变化趋势相似，但吡格列酮组与对照组、GW9662组与吡格列酮组比较，差异均无统计学意义（P>0.05）。结论 PPARγ激动剂可通过上调PPARγ表达，减少PPAF刺激所致的促炎症细胞因子的产生，从而抑制单核细胞的炎症反应。

关键词: 过氧化物酶体增殖物激活受体γ, 过氧化物酶体增殖物激活受体γ激动剂, 急性胰腺炎, 胰腺炎相关性腹水

Abstract:

Objective To investigate the effects of peroxisome proliferator-activated receptor-gamma (PPARγ) agonist on inflammatory response in monocytes. Methods Human monocytes THP-1 cells were cultured in vitro, and were divided into control group, experiment group, pioglitazone group and GW9662 group. Cells in control group were treated with culture fluid, cells in experiment group were stimulated by pancreatitis associated ascetic fluid (PAAF), 20 μmol/L PPARγ agonist pioglitazone was used before treatment with PAAF in pioglitazone group, and cells were treated with PPARγ antagonist GW9662, pioglitazone and PAAF in order in GW9662 group. Cells in each group were collected 6 h after treatment, Real-Time PCR was employed to detect the expression of proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA, and the expression of PPARγ mRNA and protein was determined by RT-PCR and Western blotting respectively. Results After stimulation with PAAF, the relative expression of TNF-α and IL-6 mRNA was significantly higher, and the relative expression of PPARγ mRNA was significantly lower in experiment group, pioglitazone group and GW9662 group than in control group (P<0.05). The relative expression of TNF-α and IL-6 mRNA was significantly lower, and the relative expression of PPARγ mRNA was significantly higher in pioglitazone group and GW9662 group than in experiment group (P<0.05). The relative expression of TNF-α and IL-6 mRNA was significantly higher, and the relative expression of PPARγ mRNA was significantly lower in GW9662 group than in pioglitazone group (P<0.05). The change of expression of PPARγ protein was in line with that of PPARγ mRNA in each group, and there was no significant difference in the expression of PPARγ protein between pioglitazone group and control group and between GW9662 group and pioglitazone group (P＞0.05). Conclusion PPARγ agonist may up-regulate the expression of PPARγ mRNA, decrease the production of proinflammatory cytokines stimulated by PPAF, and inhibit the inflammation in monocytes.

Key words: peroxisome proliferator-activated receptors gamma, peroxisome proliferator-activated receptors gamma agonist, acute pancreatitis, pancreatitis associated ascetic fluid