基础医学与临床 ›› 2016, Vol. 36 ›› Issue (7): 902-906.

• 研究论文 • 上一篇    下一篇

罗格列酮通过减少Th17细胞极化减轻LPS诱导的小鼠急性肺损伤

张小瑜1,赵燕2,王导新3   

  1. 1. 重庆医科大学附属第二医院呼吸内科
    2. 重庆医科大学第二临床医院呼吸内科
    3. 重庆医科大学附属第二医院
  • 收稿日期:2015-12-14 修回日期:2016-03-27 出版日期:2016-07-05 发布日期:2016-06-22
  • 通讯作者: 王导新 E-mail:wangdaoxin1@163.com
  • 基金资助:
    国家自然科学基金资助项目

Rosiglitazone attenuates LPS-induced mice acute lung injury by reducing polarization of Th17 cells

  • Received:2015-12-14 Revised:2016-03-27 Online:2016-07-05 Published:2016-06-22
  • Contact: Dao-xin WANG E-mail:wangdaoxin1@163.com

摘要: 目的 探讨罗格列酮(RSG)对急性肺损伤(ALI)小鼠的作用及可能的机制。方法 24只BALB/c小鼠,随机分为对照组(control)、模型组(LPS)、罗格列酮干预组(RSG)和GW9662拮抗组(GW9662),每组6只。分别检测支气管肺泡灌洗液(BALF)中炎性细胞分类计数和炎性因子水平、HE染色观察肺组织病理改变,Q-PCR和Western blot分别检测Th17细胞核转录因子RORγt及PPARγ的mRNA和蛋白表达。结果 与对照组比较,模型组BALF中性粒细胞比例和炎性因子水平均显著增高(P<0.05);肺组织RORγt高表达(P<0.05)。接受罗格列酮干预小鼠PPARγ明显增高,炎症指标均较模型组减轻(P<0.05),同时伴有RORγt表达降低。GW9662显著拮抗罗格列酮的保护作用,小鼠肺组织炎性反应显著,RORγt基因的mRNA和蛋白水平均较罗格列酮组回升(P<0.05)。结论 罗格列酮可通过活化PPARγ,进而抑制Th17细胞的分化减轻由LPS诱导的小鼠急性肺损伤。

Abstract: Objective To investigate the effect of rosiglitazone(RSG) on acute lung injury (ALI) murine model and to explore the possible mechanism. Methods BLAB/c (n=24) mice were randomized into control group, ALI model group, RSG group and GW9662 group. The percentages of the inflammation cells in the bronchoalveolar lavage fluid (BALF) and the histopathological changes of the lung tissues were examined to reflex the degree of inflammation. Meanwhile, the levels of inflammatory cytokines were measured by ELISA. The expression of RORγt and PPARγ at mRNA and protein levels in the lung tissues was determined by RT-qPCR and Western blotting respectively. Results Compared with control group, the percentage of neutrophils and the contents of the inflammatory cytokines in LPS group were significantly increased in BALF(P<0.05). Meanwhile, elevated mRNA and protein levels of RORγt suggested increased number of Th17 cells. Compared with LPS group, the degree of lung inflammation decreased in RSG group accompanied with low expression of RORγt and high expression of PPARγ(P<0.05). GW9662 significantly antagonized the protective effect of rosiglitazone, showing obvious mouse lung tissue inflammation ,and higher mRNA and protein levels of RORγt as compared with RSG group(P<0.05). Conclusions Rosiglitazone attenuates lung inflammation by regulating the polarization of Th17 cells in a murine ALI model induced by LPS.